Paradoxical down-regulation and desensitization of beta2-adrenoceptors by exogenous progesterone in female asthmatics

Abstract: We have demonstrated previously that exogenous progesterone, but not estrogen, up-regulated lymphocyte beta2-adrenoceptors (beta2-AR) when given during the follicular phase in healthy women. Female asthmatics exhibit loss of the cyclical pattern of beta2-AR regulation seen in healthy women, in that there is no luteal phase rise in beta2-AR. It has been postulated that abnormal cyclical regulation of beta2-AR might be a possible mechanism for premenstrual asthma. In this study, we were interested to see how exogenous female sex-steroid hormones altered beta2-AR regulation in female asthmatics during the follicular phase, when endogenous hormone levels are normally low. Seven nonsmoking female subjects with mild asthma, with a mean (SEM) age of 26 (2) years and FEV1 of 94.7% (6.4) of predicted, completed this randomized, double-blind, crossover study. They were evaluated at two successive menstrual cycles, during the follicular phase (day 1 to 6). They were randomized to receive single oral doses of either ethinyl estradiol (ethinyloestradiol), 50 microg, or medroxyprogesterone, 10 mg. Lymphocyte beta2-AR parameters were evaluated at baseline (T0), 24 h (T24), and 72 h (T72) after ingestion. Baseline levels of progesterone and estradiol were comparable on both cycles. Receptor binding density (log Bmax; fmol/10(6) cells) decreased significantly after progesterone but not after estrogen at T24: amounting to a 1.34-fold mean difference (95% confidence interval [CI], 1.01 to 1.78) between T24 vs T0 with progesterone. Comparing Bmax for progesterone with estrogen at T24 amounted to a 1.25-fold significant difference (95% CI, 1.00 to 1.56). This was associated with a trend (p=0.06) toward a lower cyclic-adenosine monophosphate (AMP) response to isoproterenol hydrochloride (isoprenaline) 10(-4) M (Emax) at T24 vs T0 with progesterone. Receptor binding affinity (Kd) was not altered by either treatment. These results show that exogenous progesterone, but not estrogen, given during the follicular phase, decreased beta2-AR density and cyclic-AMP response in female asthmatics, in contrast to the previously observed up-regulating effect of progesterone seen in healthy women. This paradoxical effect of progesterone in female asthmatics suggests an abnormal regulation of beta2-AR and might be a possible mechanism for premenstrual asthma when progesterone levels are high during this period of the cycle.


Extended clomiphene citrate (CC) and prednisone for the treatment of chronic anovulation resistant to CC alone

John D. Isaacs

University of Mississippi Medical Center

Abstract:
OBJECTIVE: To evaluate effectiveness and safety of a regimen of extended clomiphene citrate (CC) and prednisone for patients who fail treatment with CC alone.

DESIGN: Retrospective observational analysis.

SETTING: University-based tertiary infertility center.

PATIENT(S): Twenty-four anovulatory patients who failed to ovulate after CC 150 mg administered for 5 days.

INTERVENTION(S): Treatment consisted of CC given on cycle days 3 through 9 (extended) at a starting dose of 100 to 150 mg/d. Additionally, patients were given prednisone 5 mg orally each night throughout the cycle.

MAIN OUTCOME MEASURE(S): Ovulation was confirmed by luteal serum P. Pregnancy was confirmed by rising hCG levels and transvaginal ultrasound.

RESULT(S): A total of 60 cycles were available for review. Forty-four of these cycles were ovulatory (73%) and 11 patients (46%) conceived on this therapy. Logistic (two-parameter) pregnancy occurrence over time (cycles) revealed a maximum pregnancy probability of 0.66 and a cycle fecundity of 0.36. No complications of therapy were noted.

CONCLUSION(S): Clomiphene citrate-resistant anovulatory patients have high rates of ovulation and pregnancy after treatment with extended CC and prednisone. This therapy offers a potential reduction in cost and risk and should be considered in this group of patients before gonadotropin stimulation or surgery.


Interleukin-8 in urine: a new diagnostic parameter for intra-amniotic infection after premature rupture of the membranes

Abstract: Interleukin-8 (IL-8), a 72 amino acid peptide secreted by cells of the immune system and of the amnion, chorion and decidua, was measured in women in late pregnancy. IL-8 was detected in the urine of 91 of 104 women with premature rupture of the fetal membranes, with values exceeding 1000 ng/L in cases of severe intra-amniotic infection. Women with urinary tract infections were excluded. The routine measurement of IL-8 in urine, together with C-reactive protein in serum, thus provides a low risk and technically simple approach to the assessment of intra-amniotic infection.

British Journal of Obstetrics and Gynaecology


Time to pregnancy and preterm delivery

Time to pregnancy and preterm delivery

D D Baird

Epidemiology Branch, National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709, USA

M Hedegaard

Abstract:
OBJECTIVE: To test whether subfertile women may be at higher risk of preterm delivery.

METHODS: We used data from two population-based cohort studies on risk factors and pregnancy outcome for approximately 20,000 deliveries in three major Danish obstetric departments. The Aalborg-Odense study comprised all pregnant women attending routine antenatal care at two obstetric departments from 1984 to 1987. In all, 11,850 women (86%) filled in a questionnaire at about 36 weeks' gestation. The Aarhus study addressed women at the routine visit near 16 weeks' gestation from 1989 to 1991; a study questionnaire was returned by 6857 (80%). Both studies excluded women with chronic illnesses, multiple fetuses, and inability to speak Danish. Only women with planned pregnancies were included in the analysis. In all, 8855 and 3985 women from Aalborg-Odense and Aarhus, respectively, were eligible for the analyses. In both cohorts, women were categorized according to their waiting time to pregnancy (0-6 months, 7-12 months, and greater than 1 year) and according to examination or treatment for infertility (yes, no). Preterm delivery was defined as birth before 37 completed weeks.

RESULTS: Compared with women who tried for 6 months or less before they conceived, women who tried for 7-12 months had 1.3 times (95% confidence interval [CI] 0.8, 2.1) the adjusted risk of preterm delivery in both cohorts, and women with a time to pregnancy of greater than 12 months had adjusted relative risks for preterm delivery of 1.6 (95% CI 1.1, 2.2) for Aalborg-Odense and 1.7 (95% CI 1.1, 2.6) for Aarhus. The results remained similar after excluding women with infertility treatment.

CONCLUSIONS: Pregnant women with subfertility and clinically defined infertility are more prone to preterm delivery, even in the absence of infertility treatment.


Classification of normogonadotropic infertility: polycystic ovaries diagnosed by ultrasound versus endocrine characteristics of polycystic ovary syndrome

Abstract:
OBJECTIVE: To investigate the predictive value of polycystic ovaries for endocrine signs of polycystic ovary syndrome (PCOS).

DESIGN: Controlled descriptive study.

SETTING: Academic tertiary care fertility clinic.

PATIENT(S): Normogonadotropic (FSH levels between 1 and 10 mIU/mL conversion factor to SI unit, 1.0) oligomenorrheic or amenorrheic women visiting our fertility clinic and a control group of regularly cycling, healthy, normal weight volunteers recruited by advertisement.

INTERVENTION(S): Single blood samples and transvaginal sonography were performed.

MAIN OUTCOME MEASURE(S): Serum levels of FSH, LH, androstenedione (A), and T and ovarian volume, ovarian stroma density, and follicle number.

RESULT(S): In control women, the 95th percentile was calculated for ovarian volume, follicle number, and stroma count as well as endocrine parameters. The use of these upper limits of normal in the study group resulted in 217 (66%) patients with polycystic ovaries on ultrasound (defined as increased mean ovarian volume and/or mean follicle number per ovary), whereas only 120 (36%) patients exhibited elevated serum androgens (increased A and/or T concentrations) and 155 (47%) showed elevated LH levels. Sensitivity and specificity of single or combined sonographic parameters for prediction of elevated serum LH or androgen concentrations were limited.

CONCLUSION(S): In the study group of normogonadotropic oligomenorrhea or amenorrheic infertile women, we set strict cutoff levels for various criteria used in the literature for defining PCOS. Groups defined by sonographic or endocrine PCOS criteria did overlap, but sonographic parameters had limited predictive value for abnormal hormone serum levels.


Physiologic estradiol replacement therapy and cardiac structure and function in normal postmenopausal women: a randomized, double-blind, placebo-controlled, crossover trial

Abstract:
OBJECTIVE: To assess the effect of estradiol (E2) replacement therapy on cardiac structure and function in healthy postmenopausal women.

METHODS: We conducted a randomized, double-blind, placebo-controlled, crossover study of 31 healthy postmenopausal female volunteer study subjects (55-65 years) using 12 weeks of micronized E2 replacement therapy (2 mg/day). Echocardiography and Doppler techniques were used to assess the cardiac effects of E2 at rest and during graded bicycle ergometry.

RESULTS: Crossover analysis demonstrated no carryover effects of estrogen treatment (which increased serum E2 15-fold to 37.6 pmol/L) on the cardiac characteristics measured. Estradiol treatment did not affect measurements of systolic function, diastolic function, left ventricular mass, or pulmonary artery pressure at rest or during bicycle ergometry. Left ventricular end-diastolic volume at rest was slightly higher with E2 treatment (P = .03). However, this change was not reflected by changes in stroke volume, ejection fraction, or cardiac output.

CONCLUSIONS: Estrogen replacement therapy, which results in physiologic serum concentrations, does not affect cardiac structure or function in normal postmenopausal women after 12 weeks of treatment.


Pregnancy outcome after laparoscopic fimbrioplasty in nonocclusive distal tubal disease

Abstract:
OBJECTIVE: To determine pregnancy rates (PR) after fimbrioplasty and salpingostomy in nonocclusive distal tubal disease. To evaluate the relative impact of various factors using contemporary statistical analysis.

DESIGN: Prospective cohort.

SETTING: Tertiary institutional infertility clinic.

PATIENTS(S): Infertility patients.

INTERVENTION(S): Fimbrioplasty and salpingostomy.

MAIN OUTCOME MEASURE(S): Cumulative PR, monthly fecundity rates, monthly probability of pregnancy, crude PR, and cure rates.

RESULTS(S): Thirty-five percent of patients conceived with a cure rate of 72.2%, monthly probability of pregnancy of 3.9%, and monthly fecundity rate of 3.9%. Cumulative PRs were 22%, 35%, and 58% at 6, 12, and 24 months, respectively. Pairwise comparisons (unilateral, bilateral, or either) failed to detect any statistical difference between the salpingostomy and fimbrioplasty groups. Salpingostomy patients initially may have a higher tendency to become pregnant but appear to lose that advantage after the first few months. When patients with tubo-ovarian adhesions are excluded from the analysis, patients who underwent a bilateral salpingostomy as their sole procedure had better outcome compared with those who only underwent bilateral fimbrioplasty. There was no significant association between pregnancy outcome and the presence of endometriosis, other infertility factors, or tubo-ovarian adhesions. The staging of adnexal adhesions and endometriosis did not predict pregnancy outcome.

CONCLUSION(S): Laparoscopic fimbrioplasty and salpingostomy are clinically efficacious for the treatment of nonocclusive distal tubal disease. After accounting for statistical interactions of various factors among them, no particular association with pregnancy outcome could be identified. This illustrates the need for a revision of the classification of patients with distal tubal disease.


A pregnant woman with clear cell adenocarcinoma of the ovary arising from endometriosis and with benign and borderline adenofibroma of the clear cell and endometrioid types

Abstract: We encountered a case of ovarian cancer in a 33-year-old, 8-week pregnant woman. Histological examination revealed both a transitive form of ovarian endometriosis with marked decidual changes due to pregnancy and clear cell carcinoma. Benign and borderline clear cell adenofibroma and benign and borderline endometrioid adenofibroma were also found. Parts of these adenofibromas showed transformation to clear cell carcinoma. This case suggests that clear cell carcinoma can arise from clear cell adenofibromas and/or ovarian endometriosis, even in young patients.

European Journal of Obstetrics, Gynecology, and Reproductive Biology


Unexplained infertility: evaluation of the luteal phase; results of the National Center for Infertility Research at Michigan

Abstract:
OBJECTIVE: To evaluate the luteal phase in women with rigorously defined unexplained infertility.

DESIGN: Prospective study.

SETTING: National Center for Infertility Research at Michigan.

PATIENT(S): Evaluation of 1,885 women with infertility identified 12 women who met the rigorously defined criteria for unexplained infertility: [1] infertility of > or = 24 months duration, with no male factor, anatomic-functional disorders of the reproductive tract, or immunologic infertility; [2] normal body mass index (BMI); [3] ovulatory cycles ranging from 26 to 32 days; [4] normal luteal phase determined by endometrial biopsy; and [5] normal baseline hormonal profile. Controls (n = 12) were healthy, parous women with normal ovulatory cycles, normal hormonal screen, and were matched for age and BMI to patients.

MAIN OUTCOME MEASURE(S): Pattern of follicular growth rate and luteal phase hormonal profile.

RESULT(S): Women with unexplained infertility did not differ in menstrual cycle characteristics, follicular growth rate or mean preovulatory follicle diameter, or endometrial biopsy dating. The mean levels of P tended to be lower in the unexplained infertility group throughout the luteal phase, but only the midluteal interval reached statistical significance. Luteal phase mean integrated P or urinary PDG levels of unexplained infertility women did not differ from those of fertile controls. The ratio of integrated E2:P also was significantly greater in women with unexplained infertility than in fertile controls.

CONCLUSION(S): Women with rigorously defined unexplained infertility have subtle hormonal anomalies during the luteal phase when compared with fertile controls.


Medroxyprogesterone interferes with ovarian steroid protection against coronary vasospasm

K Miyagawa

Oregon Regional Primate Research Center, Oregon 97006, USA.

Abstract: Cardiovascular disease, the major cause of death in post-menopausal women, can be reduced by replacement of ovarian steroid hormones. To compare medroxyprogesterone with progesterone as the progestin in hormone replacement therapy from the standpoint of coronary artery vasospasm, we treated ovariectomized rhesus monkeys with physiological levels of estradiol-17 beta in combination with medroxyprogesterone or progesterone for four weeks. Coronary vasospasm in response to pathophysiological stimulation without injury showed that progesterone plus estradiol protected but medroxyprogesterone plus estradiol failed to protect, allowing vasospasm. We conclude that medroxyprogesterone in contrast to progesterone increases the risk of coronary vasospasm.


Efficacy and safety of finasteride?

Efficacy and safety of finasteride?


Ovarian atypical endometriosis: its close association with malignant epithelial tumours

Abstract: The incidence of ovarian atypical endometriosis and its association with malignant epithelial tumours in a consecutive series of cases during the period 1987 to 1995 were studied. Atypical glandular changes were observed in four (1.7%) of 255 ovarian endometriosis cases and one patient with ovarian atypical endometriosis developed subsequent endometrioid carcinoma in the abdominal wall. Fifty-four (24.1%) of the 224 ovarian cancers were associated with ovarian endometriosis; 21 with typical and 33 with atypical endometriosis. Clear cell carcinomas and endometrioid carcinomas were most frequently associated with endometriosis, with 54% (27 of 50 cases) and 41.9% (13 of 31), respectively. Atypical endometriosis was found in 18 clear cell carcinomas, in seven endometrioid carcinomas, in four serous carcinomas, in three mucinous borderline tumours, and in one serous borderline tumour. In 13 cases, the atypical endometriosis was in contiguity with malignant epithelial tumours. We consider that atypical endometriosis possesses a precancerous potential or is most frequently associated with clear cell and endometrioid carcinomas. Close screening of cellular atypia or hyperplasia in ovarian endometriosis and careful long-term follow-up of patients with atypical endometriosis is required.


Practice patterns among reproductive endocrinologists: the infertility evaluation

Abstract:
OBJECTIVE: To determine how board-certified reproductive endocrinologists vary in their approach to the clinical tests performed on the infertile couple.

DESIGN: A cross-sectional study to assess differences in the approach to evaluating the infertile couple.

SETTING: A population-based national survey.

PARTICIPANT(S): United States board-certified reproductive endocrinologists.

MAIN OUTCOME MEASURE(S): The frequency of clinical tests and evaluation procedures by physician age, sex, size and setting of practice, institutional affiliation, and geographic location.

RESULT(S): The overall response rate was 84%. Although the majority of practitioners routinely order a semen analysis (99.9%), an assessment of ovulation (98%), a hysterosalpingogram, (HSG; 96%), laparoscopy (89%), and a postcoital test (PCT, 79%), there was less agreement regarding hormonal testing (range, 22% [LH] to 66% [PRL]), use of pelvic ultrasounds (55%), hysteroscopy (53%), cervical cultures (range, 24% to 54%), and antisperm antibody testing (24%). Compared with male colleagues, female physicians order two to three times more cervical cultures and endometrial biopsies. Serum hormonal testing was two to three times more commonly ordered by younger (< 40 years) compared with older physicians, and physicians in private practice twice as frequently ordered hormonal testing, cervical cultures, PCTs, and antisperm antibody studies compared with their academic-affiliated colleagues. Western U.S. physicians order hormonal tests and cervical cultures 50% less often than their midwest and eastern counterparts.

CONCLUSION(S): Trained specialists rely heavily on five "traditional" infertility tests: semen analysis, an assessment of ovulation, HSG, laparoscopy, and PCT. With regard to additional modes of testing, there is marked variability by physician sex, age, type of practice, and geographic location.


The assessment of normal and abnormal luteal function by transvaginal color Doppler sonography

Abstract:
OBJECTIVE: To evaluate intraovarian resistance index (RI) in 47 healthy fertile volunteers with ovulatory cycles, 28 patients with luteal phase defect (LPD) and four patients with luteinized unruptured follicle (LUF Sy).

STUDY DESIGN: Transvaginal color Doppler assessment of the follicular and corpus luteum blood flow and plasma progesterone (P) levels were obtained in each patient.

RESULTS: Significantly higher intraovarian artery RI (< 0.001) was obtained for LPD group than for controls during the luteal phase. In the control group both follicular and corpus luteum RI were significantly lower (P < 0.001) on the dominant side, while in LPD group no difference (P > 0.05) between the sides occurred. Mean P levels were significantly lower (P < 0.001) in the LPD group (6.9 +/- 2.3 ng/ml) than in controls (24.1 +/- 11.4 ng/ml). In all the LPD patients histopathology revealed delayed endometrial pattern, while normal endometrial dating was found in all the evaluated patients form the control group (n = 15). In the patients with LUF Sy (n = 4) similar RI values were obtained in the follicular and corpus luteum phase. There was no difference between the sides in terms of the intraovarian RI, while subnormal values of P were obtained in all the examined patients (14.1 +/- 6.2 ng/ml).

CONCLUSIONS: Transvaginal color Doppler may predict the function capacity of the corpus luteum.


What is the radiation exposure to patients during a gynecoradiologic procedure?

Abstract:
OBJECTIVE: To evaluate the risk of radiation exposure to infertility patients during a gynecoradiologic procedure.

DESIGN: Retrospective clinical study.

SETTING: Medical school-affiliated infertility center.

PATIENT(S): Three hundred thirty-two consecutive infertility patients undergoing a gynecoradiologic procedure.

INTERVENTION(S): Patients underwent a gynecoradiologic procedure as part of their infertility workup and the fluoroscopic exposure time was analyzed.

MAIN OUTCOME MEASURE(S): The fluoroscopic exposure (rad time) during gynecoradiologic procedures, including hysterosalpingogram (HSG), selective salpingography, tubal catheterization, and others.

RESULT(S): The rad time (mean +/- SD) was 63 +/- 54 seconds for normal HSG (n = 94, range 17 to 404 seconds), 100 +/- 61 seconds for abnormal HSG (n = 53, range 28 to 272 seconds), 111 +/- 57 seconds for unilateral selective salpingography (n = 36, range 31 to 324 seconds), 142 +/- 74 seconds for bilateral selective salpingography (n = 87, range 40 to 430 seconds), 176 +/- 77 seconds for unilateral tubal catheterization (n = 27, range 70 to 342 seconds), and 239 +/- 82 seconds for bilateral tubal catheterization (n = 30, range 110 to 381 seconds). Five patients had other procedures, such as lysis of intrauterine adhesions (n = 2) and resection of an uterine septum (n = 3), for which the rad time was in a range of 180 to 300 seconds.

CONCLUSION(S): The radiation exposure of patients during a gynecoradiologic procedure, using previously described standard techniques, is well within established margins of safety.


Changing trends in the diagnosis of endometriosis: a comparative study of women with pelvic endometriosis presenting with chronic pelvic pain or infertility

W P Dmowski

University of Arkansas for Medical Sciences

Abstract:
OBJECTIVE: To compare demographic, epidemiologic, and medical data and to evaluate diagnostic trends in women with endometriosis and chronic pelvic pain symptoms or endometriosis and infertility.

DESIGN: Retrospective analysis.

SETTING: Institute for the Study and Treatment of Endometriosis.

PATIENT(S): Six hundred ninety-three consecutive patients with endometriosis and chronic pelvic pain (n = 357) or endometriosis and infertility (n = 336).

INTERVENTION(S): None.

MAIN OUTCOME MEASURE(S): Demographic and epidemiologic parameters, diagnostic trends.

RESULT(S): Women with pelvic symptoms were younger, had less formal education, more frequent family history, and higher frequency and intensity of pelvic complaints. Mean ages at first symptom and diagnosis were lower in the pain group, but stage of endometriosis at first diagnosis was more advanced. The mean "diagnostic delay" was longer in the pelvic pain than in the infertile group (6.35 versus 3.13 years), but it decreased during three consecutive 5-year intervals in both groups, and there was also a gradual decrease in the frequency of advanced endometriosis at the time of first diagnosis.

CONCLUSION(S): Demographic and epidemiologic parameters in women with endometriosis differ, depending whether chronic pelvic pain or infertility are the presenting symptoms. In the pain group, diagnostic delay is longer and endometriosis at diagnostic laparoscopy more advanced, indicating progressiveness of the disease. During the last 15 years, diagnostic delay steadily decreased and the frequency of advanced endometriosis at first diagnosis declined.


Effects of clomiphene citrate on the endometrial thickness and echogenic pattern of the endometrium

Abstract:
OBJECTIVE: To study the effects of clomiphene citrate (CC) on the endometrium by ultrasound and to reveal the echogenic difference between the control cycle and the CC cycle.

DESIGN: Retrospective study of patients before and during a CC treatment.

SETTING: Department of Obstetrics and Gynecology, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan.

PATIENT(S): Seventy-nine infertile women who had a spontaneous ovulation and a normal luteal function.

INTERVENTION(S): Patients received 50 mg/d CC between days 5 and 9 of the menstrual cycle.

MAIN OUTCOME MEASURE(S): Endometrial thickness, echogenic pattern of the endometrium, serum E2 content, and E2 and P receptor contents in the endometrium.

RESULT(S): Endometrial thickness was significantly thinner during the CC cycle (7.6 +/- 1.4 mm, mean +/- SD, n = 79) than during the control cycle (8.5 +/- 1.7 mm, n = 79) on late proliferative days, but there was no significant difference on midsecretory days (10.8 +/- 2.2 mm during the CC cycle, n = 79; 11.2 +/- 2.2 mm during the control cycle, n = 79). The echogenic patterns, however, were different between the two cycles on midsecretory days. Moreover, the incidence in which patients showed a grade 3 endometrium on midsecretory days was significantly higher during the conceived CC cycle compared with the not-conceived CC cycle. Serum E2 levels were significantly higher, but E2 receptor contents in the endometrium were significantly lower during the CC cycle (67 +/- 46 fmol/mg, n = 13) compared with the control cycle (123 +/- 89 fmol/mg, n = 15) on late proliferative days.

CONCLUSION(S): Clomiphene citrate affected the echogenic pattern of the endometrium, and most of the endometrium showed a grade 3 pattern on midsecretory days during the conceived CC cycle. Under the CC treatment, the comfortable endometrium for embryos might be different from the control cycle.


Psychobiology of postpartum mood disorders

K L Wisner

Women's Services, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.

Abstract: Postpartum mood disorders are common. The clustering of mood-disorder episodes after birth compels a search for factors particularly potent during childbearing. In this article, the complex relationships between the dynamic postbirth physiological environment and mood disorder are discussed. Available studies show a lack of evidence that serum levels of gonadal hormones account for mood disturbance in women. However, substantial amounts of data demonstrate their ability to modulate other neuroendocrine systems. Alterations in hypothalamic-pituitary-adrenal (HPA) axis function attributable to childbearing show remarkable similarity to those observed in depressed women. Postpartum women are also at increased risk for hypothalamic-pituitary-thyroidal (HPT) axis dysfunction that may increase affective-disorder vulnerability. A decreased rate


Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies)

Abstract:
OBJECTIVE: To determine whether treatment with low dose aspirin and heparin leads to a higher rate of live births than that achieved with low dose aspirin alone in women with a history of recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies), lupus anticoagulant, and cardiolipin antibodies (or anticardiolipin antibodies).

DESIGN: Randomised controlled trial.

SETTING: Specialist clinic for recurrent miscarriages.

SUBJECTS: 90 women (median age 33 (range 22-43)) with a history of recurrent miscarriage (median number 4 (range 3-15)) and persistently positive results for phospholipid antibodies.

INTERVENTION: Either low dose aspirin (75 mg daily) or low dose aspirin and 5000 U of unfractionated heparin subcutaneously 12 hourly. All women started treatment with low dose aspirin when they had a positive urine pregnancy test. Women were randomly allocated an intervention when fetal heart activity was seen on ultrasonography. Treatment was stopped at the time of miscarriage or at 34 weeks' gestation.

MAIN OUTCOME MEASURES: Rate of live births with the two treatments.

RESULTS: There was no significant difference in the two groups in age or the number and gestation of previous miscarriages. The rate of live births with low dose aspirin and heparin was 71% (32/45 pregnancies) and 42% (19/45 pregnancies) with low dose aspirin alone (odds ratio 3.37 (95% confidence interval 1.40 to 8.10)). More than 90% of miscarriages occurred in the first trimester. There was no difference in outcome between the two treatments in pregnancies that advanced beyond 13 weeks' gestation. Twelve of the 51 successful pregnancies (24%) were delivered before 37 weeks' gestation. Women randomly allocated aspirin and heparin had a median decrease in lumbar spine bone density of 5.4% (range -8.6% to 1.7%).

CONCLUSION: Treatment with aspirin and heparin leads to a significantly higher rate of live births in women with a history of recurrent miscarriage associated with phospholipid antibodies than that achieved with aspirin alone.


Serum cholesterol concentration and postpartum depression. Oestrogen may have been a confounder


Population-based study of risk of venous thromboembolism associated with various  oral contraceptives

Abstract:
Background: Four studies published since December, 1995, reported that the incidence of venous thromboembolism (VTE) was higher in women who used oral contraceptives (OCs) containing the third-generation progestagens gestodene or desogestrel than in users of OCs containing second-generation progestagens. However, confounding and bias in the design of these studies may have affected the findings. The aim of our study was to re-examine the association between risk of VTE and OC use with a different study design and analysis to avoid some of the bias and confounding of the earlier studies.

Methods: We used computer records of patients from 143 general practices in the UK. The study was based on the medical records of about 540,000 women born between 1941 and 1981. All women who had a recorded diagnosis of deep-vein thrombosis, venous thrombosis not otherwise specified, or pulmonary embolus during the study period, and who had been treated with an anticoagulant were identified as potential cases of VTE. We did a cohort analysis to estimate and compare incidence of VTE in users of the main OC preparations, and a nested case-control study to calculate the odds ratios of VTE associated with use of different types of OC, after adjustment for potential confounding factors. In the case-control study, we matched cases to controls by exact year of birth, practice, and current use of OCs. We used a multiple logistic regression model that included body-mass index, number of cycles, change in type of OC prescribed within 3 months of the event, previous pregnancy, and concurrent disease.

Findings: 85 women met the inclusion criteria for VTE, two of whom were users of progestagen-only OCs. Of the 83 cases of VTE associated with use of combined OCs, 43 were recorded as deep-vein thrombosis, 35 as pulmonary thrombosis, and five as venous thrombosis not otherwise specified. The crude rate of VTE per 10,000 woman-years was 4.10 in current users of any OC, 3.10 in users of second-generation OCs, and 4.96 in users of third-generation preparations. After adjustment for age, the rate ratio of VTE in users of third-generation relative to second-generation OCs was 1.68 (95% CI 1.04-2.75). Logistic regression showed no significant difference in the risk of VTE between users of third-generation and second-generation OCs. Among users of third-generation progestagens, the risk of VTE was higher in users of desogestrel with 20 g ethinyloestradiol than in users of gestodene or desogestrel with 30 g ethinyloestradiol. With all second-generation OCs as the reference, the odds ratios for VTE were 3.49 (1.21-10.12) for desogestrel plus 20 g ethinyloestradiol and 1.18 (0.66-2.17) for the other third-generation progestagens.

Interpretation: The previously reported increase in odds ratio associated with third-generation OCs when compared with second-generation products is likely to have been the result of residual confounding by age. The increased odds ratio associated with products containing 20 micrograms ethinyloestradiol and desogestrel compared with the 30 micrograms product is biologically implausible, and is likely to be the result of preferential prescribing and, thus, confounding.


Retroperitoneal endometriosis infiltrating the utero-sacral ligaments. Technique and results of laparoscopic surgery

Abstract:
Objective: The goal of this study is to assess the efficiency of laparoscopic surgical treatment of pain for patients presenting deep endometriosis located on the uterosacral ligaments.

Study Design: We analysed a continuous series of 36 patients treated by operative laparoscopy between January 1993 and April 1995. In all these cases treatment consisted of resection of all the uterosacral ligament(s) together with exeresis of all other endometriotic lesions.

Results: The results were assessed for all the patients with a minimum follow-up of one year. Patients who presented dysmenorrhea (29 cases) improved in 89.7% of cases (26 patients). Out of the 26 patients who presented deep dyspareunia, improvement was evident for 92.3% of cases (24 patients). The chronic pelvic pain suffered (17 cases) improved in 88.2% of cases (15 patients). Patients who benefited from an improvement rated it excellent or satisfactory in 80% of cases.

Conclusion: These results demonstrate that provided the surgeon is highly skilled in laparoscopy, operative laparoscopy is efficient for the treatment of patients presenting painful symptoms related to deep endometriotic implants located on the uterosacral ligaments.

Journal de gynecologie, obstetrique et biologie de la reproduction


DIR Jahrbuch 1996 (Deutsches IVF-Register Annual Report 1996)

Abstract: Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 1996. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).


Cervical mucus and their functions

Cervical mucus and their functions

Journal of the Irish Colleges of Physicians and Surgeons


Depression during pregnancy and the puerperium

Abstract: Epidemiologic studies demonstrate a twofold higher rate of depression in women than in men. The childbearing years are a time of increased risk for onset of depression in women. Pregnancy, miscarriage or pregnancy loss, infertility, and the postpartum period may challenge a woman's mental health. Virtually no life event rivals the neuroendocrine and psychosocial changes associated with pregnancy and childbirth. This paper provides a brief overview of depression during pregnancy and the postpartum period. Incidence, risk factors, and complications of depression during pregnancy and the puerperium are discussed to aid the clinician in early identification of at-risk patients. Treatment recommendations are also provided based on the available literature, clinical experience, and consideration of the possible special circumstances (i.e., breast-feeding) of this population of women.


Measuring contraceptive effectiveness: a conceptual framework


C-reactive protein concentration in the sera of pregnant women with imminent premature parturition and preterm amniorrhea

Abstract: C-reactive protein (CRP) levels were evaluated during spontaneous labour, in imminent premature parturition (IPP) and after preterm rupture of oocyst membranes (PROM). Increasing CRP level during spontaneous labour was found in 16.6% parturients. Elevated CRP level in patients with IPP makes it impossible to predict premature labour. In parturients with PROM, increase in CRP level makes further infection predictable only in a few cases.

Roczniki Akademii Medycznej W Bialymstoku (1995)


Postpartum depressive disorders

Postpartum depressive disorders

Abstract: Despite the high prevalence of postpartum depressive disorders, many signs and symptoms of this illness are dismissed as normal physiologic changes associated with childbirth. Prompt recognition and treatment are imperative in order to limit the negative impact on both the mother and infant. Mood disturbances may have a minor functional impact that respond well to social support (eg. postpartum blues) or cause significant functional compromise requiring more aggressive therapy (eg. postpartum depression). The most extreme case of postpartum depressive disorder, postpartum psychosis, occurs when patients develop psychosis, mania, or thoughts of infanticide. Depression during pregnancy or the presence of risk factors suggests the need for careful follow-up. If postpartum depression develops, psychotherapy is the first-line treatment. Antidepressant treatment may be warranted for some patients, and the risks and benefits to both the mother and infant should be considered in the decision to institute pharmacotherapy.


Urinary tract endometriosis treated by laparoscopy

Abstract:
OBJECTIVE: To evaluate the efficacy of the laparoscopic approach for the diagnosis and treatment of severe urinary tract endometriosis.

DESIGN: Retrospective review of 28 cases of severe urinary tract endometriosis.

SETTING: Center for Special Pelvic Surgery, a tertiary referral center.

PATIENT(S): Between October 1989 and September 1994, we treated 28 women who had deeply infiltrating urinary tract endometriosis (bladder, 7, ureter, 21).

INTERVENTION(S): All procedures were performed laparoscopically.

MAIN OUTCOME MEASURE(S): Postoperative urinary function, pain relief, and complications.

RESULT(S): Those who had vesical endometriosis underwent partial cystectomy and primary repair. Partial ureteral obstruction was found in 17 women; 10 underwent ureterolysis and excision of endometriosis, and 7 had partial wall resection. Four patients with ureter involvement had complete obstruction. Three underwent partial resection and ureteroureterostomy, and one had ureteroneocystostomy. The rate of ureteral endometriosis in the present series is higher than that reported previously.

CONCLUSION(S): Severe infiltrative endometriosis of the bladder and the ureter can present without specific symptoms and can cause silent compromise of renal function. We demonstrated that the laparoscopic approach is safe and effective in the diagnosis and treatment of this entity.


Reduction of adhesions after uterine myomectomy by Seprafilm membrane (HAL-F): a blinded, prospective, randomized, multicenter clinical study. Seprafilm Adhesion Study Group

Abstract:
OBJECTIVE: To assess the safety and efficacy of Seprafilm (HAL-F), Bioresorbable Membrane, (Genzyme Corporation, Cambridge, MA) in reducing the incidence, severity, extent, and area of uterine adhesions after myomectomy.

DESIGN: Prospective, randomized, blinded, multicenter study. Adhesion reduction was assessed by an independent, blinded, gynecologic surgeon who reviewed videotapes of each patient's second-look laparoscopy.

SETTING: Nineteen institutions across the United States.

PATIENT(S): One hundred twenty-seven women undergoing uterine myomectomy with at least one posterior uterine incision > or = 1 cm in length.

INTERVENTION(S): Patients were randomized to treatment with Seprafilm or to no treatment at the completion of the myomectomy.

MAIN OUTCOME MEASURE(S): The incidence, severity, extent, and area of uterine adhesions at second-look laparoscopy.

RESULT(S): The incidence, measured as the mean number of sites adherent to the uterine surface, was significantly less in treated patients (4.98 +/- 0.52 [mean +/- SEM] sites) than in no treatment patients (7.88 +/- 0.48 sites) as were the mean uterine adhesion severity scores (1.94 +/- 0.14 versus 2.43 +/- 0.10; treatment versus no treatment, respectively), mean extent scores (1.23 +/- 0.12 versus 1.68 +/- 0.10), and mean area of adhesions (13.2 +/- 1.67 versus 18.7 +/- 1.66 cm2). No adverse events occurred that were judged to be related to the use of Seprafilm.

CONCLUSION(S): In this multicenter study, treatment of patients after myomectomy with Seprafilm significantly reduced the incidence, severity, extent, and area of postoperative uterine adhesions. Additionally, Seprafilm treatment was not associated with an increase in postoperative complications.


Procreation after death or mental incompetence: medical advance or technology gone awry?

Abstract:
Objective: To review our experience with semen retrieval in men who are incompetent or dead and to formulate general medical, legal, and ethical guidelines for practitioners.
Design: Case series and literature review.
Setting: Academic. PATIENT(S): Seven incompetent or neurologically dead individuals in whom sperm retrieval was requested. INTERVENTION(S): Electroejaculation. RESULT(S): Seminal emission was induced in the two men who underwent electroejaculation. Sperm suitable for cryopreservation was obtained in one of these men. Review of the legal and ethical implications of such procedures led to development of general guidelines for determining whether gamete retrieval should be performed when requested. Issues of procreational autonomy, consideration of the decedent's wishes, and assurance of the well-being of any new life created were considered most strongly in the formation of these guidelines. CONCLUSION(S): Although the retrieval of sperm from deceased or incompetent individuals may be achieved readily, it is incumbent upon the practitioner to consider the legal and moral implications of these procedures before proceeding.


Malignant tumors arising in endometriosis: clinical-pathological study and flow cytometry analysis

Abstract:
BACKGROUND: Malignant transformation to endometriosis is a well documented phenomenon that occurs most commonly in the ovaries with cancer arising in extra-ovarian endometriosis being a rare event.

METHODS: A retrospective clinical-pathological evaluation of eleven cases with malignant tumors arising in endometriosis was performed to evaluate the prognostic impact of various factors. Nuclear DNA content (ploidy) was assessed through flow cytometric study.

RESULTS: Ovarian origin was identified in eight cases and three were associated with extra-ovarian endometriosis. Histologic type was endometrioid carcinoma in ten patients. The eleventh case had high grade endometrial stromal sarcoma. All tumors were diploid with no relation to stage, grade, or clinical outcome. The S-phase fraction (SPF) was analyzed in nine patients and no correlation could be demonstrated with any histologic parameters or clinical outcome.

CONCLUSIONS: The DNA content seems to have no association with the classical prognostic parameters in these cases.

European Journal of Obstetrics, Gynecology, and Reproductive Biology


Screening for depression in pregnancy: characteristics of the Beck Depression Inventory

W L Holcomb

Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri, USA.

Abstract:
OBJECTIVE: To determine the test characteristics of a self-report questionnaire, the Beck Depression Inventory, when used as a screening test for depression in a population of ambulatory pregnant women.

METHODS: One hundred five pregnant women completed the Beck Depression Inventory and underwent a structured interview using the National Institute of Mental Health Diagnostic Interview Schedule-version III. Current depression was diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders-III-R. A receiver operating characteristic curve was constructed for the Beck Depression Inventory score as a predictor of current depression. A table of sensitivities, specificities, predictive values, and likelihood ratios was created for various cutoff values.

RESULTS: For the 105 women enrolled, the median Beck Depression Inventory score was 8.0. Twelve women (11%) were diagnosed with current depression and had a median Beck Depression Inventory score of 25.5, compared with those without current depression, who had a median score of 8.0 (P = .001). The area under the receiver operating characteristic curve was 0.9940. Using a cutoff range of greater than 16, the sensitivity of the Beck Depression Inventory to detect current depression was 0.83, the specificity was 0.89, the positive predictive value was 0.50, and the negative predictive value was 0.98.

CONCLUSIONS: The Beck Depression Inventory can serve as a rapid screening test for depression during pregnancy. A higher cutoff value is required for pregnant women than is customarily used outside of pregnancy.


Gastrointestinal tract involvement by gynecologic diseases

R A Szucs

Virginia Commonwealth University Medical Center

Abstract: Involvement of the gastrointestinal tract by gynecologic disease processes-endometriosis, gynecologic neoplasms, inflammatory processes, and complications from radiation therapy or surgery for gynecologic tumors-may mimic primary gastrointestinal carcinoma on radiologic images. Endometriosis most often involves the anterior wall of the rectosigmoid colon, adjacent to the pouch of Douglas, and typically produces extrinsic mass effect on the serosa, with the overlying mucosa left intact. Direct extension of ovarian cancer to the colon through the subperitoneal space produces mass effect with serosal spiculation, tethering, and fixation; annular constriction; or partial or complete obstruction. Intraperitoneal seeding of ovarian carcinoma most frequently involves the colon and is seen as extrinsic masses, often with serosal spiculation and tethering. Cervical carcinoma, which most commonly spreads by direct invasion of the pelvic side wall and adjacent structures, produces serosal spiculation and circumferential narrowing. Benign ovarian or uterine tumors are purely extrinsic and have a smooth interface with the colonic wall. Tubo-ovarian abscesses are difficult to differentiate from cystic ovarian neoplasms or endometriomas. Radiation colitis causes narrowing of the rectum with intact mucosa and can be differentiated from recurrent tumor, unlike radiation-induced injury of the small bowel, which may be difficult to distinguish. Surgical adhesions produce a discrete transition point between dilated bowel proximally and nondilated distal bowel. Familiarity with the varied patterns of gastrointestinal tract involvement is important for accurate interpretation of imaging studies.

Radiographics : a Review Publication of the Radiological Society of North  America, Inc


An unsuccessful attempt to relate ovulatory disturbances to changes in bone density

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

The Journal of clinical endocrinology and metabolism


Cytokines and immuno-endocrine factors in recurrent miscarriage

K J Lim

University Department of Obstetrics and Gynaecology, Jessop Hospital for Women, Sheffield, UK.

Abstract: Recurrent miscarriage remains an enigma. The main aetiologies are endocrinological, immunological and unexplained. With the growth in molecular biology, it is now possible to look at the effect of these aetiologies in more detail, allowing greater understanding of the underlying pathogenesis.


Nutrition, hormones, and breast cancer: is insulin the missing link?

R Kaaks

Centre International de Recherche sur le Cancer

Abstract: Breast cancer incidence rates are high in societies with a Western lifestyle characterized by low levels of physical activity, and by an energy-dense diet rich in total and saturated fat and refined carbohydrates. Epidemiologic studies, so far mostly on postmenopausal women, have shown that breast cancer risk is increased in hyperandrogenic women, with decreased levels of plasma sex-hormone binding globulin, and with increased levels of testosterone and of free estrogens. This paper describes the role of hyperinsulinemia as a physiologic link between nutritional lifestyle factors, obesity, and the development of a hyperandrogenic endocrine profile, and reviews evidence that may or may not support the theory that chronic hyperinsulinemia is an underlying cause of breast cancer. An hypothesis is presented, stipulating that breast cancer risk is increased not only in hyperandrogenic postmenopausal women, but also in premenopausal women with mild hyperandrogenism and normal (ovulatory) menstrual cycles. The author suggests further investigation as to whether there is a positive association between risk of breast cancer before menopause and subclinical forms of the polycystic ovary syndrome (PCOS), and to what extent diet and physical activity during childhood, by modulating the degree of insulin resistance during adolescence, may or may not be determinants of a PCO-like hyperandrogenic endocrine profile persisting into adulthood.


Effectiveness of lactational amenorrhoea in prevention of pregnancy in Manila, the Philippines: non-comparative prospective trial

Abstract: OBJECTIVE: To determine the contraceptive efficacy of the lactational amenorrhoea method. DESIGN: Non-comparative prospective trial. SETTING: Urban Manila, the Philippines. SUBJECTS: 485 lower income, educated women with extensive experience of breast feeding. INTERVENTION: Women were offered all available contraceptives for use after birth. Those who chose the lactational amenorrhoea method were taught the method, screened for the study, and followed for 12 months to determine the risk of pregnancy when the method was used. MAIN OUTCOME MEASURES: Life table pregnancy rates during correct and incorrect use of the method, censored monthly in the event of sexual abstinence or the use of another contraceptive method. RESULTS: The lactational amenorrhoea method was 99% effective when used correctly (that is, during lactational amenorrhoea and full or nearly full breast feeding for up to six months). At 12 months the effectiveness during amenorrhoea dropped to 97%. CONCLUSIONS: The lactational amenorrhoea method provided as much protection from pregnancy as non-breast feeding women experience with non-medicated intrauterine devices and barrier methods. The contraceptive effect of lactation cannot be attributed to lactational or postpartum abstinence.


Hepatic endometriosis: a case report

Hepatic endometriosis: a case report

Abstract:
OBJECTIVE: To describe a case of hepatic endometriosis.

DESIGN: Case report.

SETTING: University hospital.

PATIENT: A 34-year-old woman with a 2-year history of cyclic right subcostal pain.

INTERVENTIONS: Gonadotropin-releasing hormone agonist (GnRH-a) therapy followed by surgical resection.

RESULTS: Ultrasonography, computed tomography scan, and magnetic resonance imaging of the liver disclosed a 6-cm diameter mass. The GnRH-a therapy for 4 months led to clinical and radiologic improvement. Surgery performed to allow pregnancy confirmed the diagnosis of hepatic endometriosis.

CONCLUSIONS: Hepatic endometriosis is uncommon. It may result from metaplasia of the peritoneum or from hematogenic or lymphatic spread.


Luteal support after in-vitro fertilization: Crinone 8%, a sustained release vaginal progesterone gel, versus Utrogestan, an oral micronized progesterone

J L Pouly

Gynaecology and Human Reproduction Department, Hotel-Dieu, Clermont-Ferrand, France.

Rayza Elizabeth Guillén Zambrano

Genetique Reproduction and Developpement

Abstract: Two progesterone presentations, a vaginal application of 90 mg progesterone per day (Crinone) or 300 mg progesterone administered orally (Utrogestan), were compared for luteal phase support of patients undergoing an in-vitro fertilization (IVF) procedure. A total of 283 patients were randomly allocated to either treatment. The treatment started within 24 h after the embryo transfer procedure and continued until day 30 in cases of implantation. Efficacy was assessed using the pregnancy and delivery rates. Safety was assessed through specific symptoms and usual safety monitoring. The pregnancy rates per transfer were not significantly different in the Crinone and Utrogestan groups at days 12 (Crinone 35.3%, Utrogestan 29.9%, P = 0.55), 30 (Crinone 28.5%, Utrogestan 25.0%, P = 0.61) and 90 (Crinone 25.9%, Utrogestan 22.9%, P = 0.69). No differences in the spontaneous abortion rates were seen thereafter. The delivery rates (number of deliveries per patient; Crinone 23.0%, Utrogestan 22.2%, P = 1.00), as well as the ratio of newborn babies per embryo transferred (Crinone 11.7%, Utrogestan 11.1%, P = 0.91), were not significantly different. Safety parameters were similar in both groups, except for drowsiness, which was more significantly frequent in the oral progesterone group than in the Crinone group at all time points. No serious adverse events were recorded in this study. The fact that Crinone matches the efficacy of the larger doses of progesterone used orally reflects an advantage of the transvaginal route of administration which avoids the metabolic inactivation of progesterone during its first liver pass.


A comparison of the ovulation method with the CUE ovulation predictor in determining the fertile period

Abstract: The purpose of this study was to compare the CUE Ovulation Predictor with the ovulation method in determining the fertile period. Eleven regularly ovulating women measured their salivary and vaginal electrical resistance (ER) with the CUE, observed their cervical-vaginal mucus, and measured their urine for a luteinizing hormone (LH) surge on a daily basis. Data from 21 menstrual cycles showed no statistical difference (T = 0.33, p = 0.63) between the CUE fertile period, which ranged from 5 to 10 days (mean = 6.7 days, SD = 1.6), and the fertile period of the ovulation method, which ranged from 4 to 9 days (mean = 6.5 days, SD = 2.0). The CUE has potential as an adjunctive device in the learning and use of natural family planning methods.

Journal of the American Academy of Nurse Practitioners


Prevention and management of osteoporosis: consensus statements from the Scientific Advisory Board of the Osteoporosis Society of Canada. 5. Physical activity as therapy for osteoporosis

Abstract:
Objective: To examine exercise as a therapy for people with osteoporosis. Options: Immobilization, standing low-load and high-load physical activities.

Outcomes: Risk of injury, quality of life, risk of falls and fractures, strength and posture and pain management. Evidence: Relevant epidemiologic studies, clinical trials and reviews were examined, including the large-scale FICSIT trial in the United States, a prospective 4-year study of women enrolled in an exercise program in Toronto and the large-scale Study of Osteoporotic Fractures. Values: Minimizing risk of injury and increasing quality of life were given a high value. BENEFITS, HARMS, And Costs: Moderate physical activity in people with osteoporosis can reduce the risk of falls and fractures, decrease pain and improve fitness and overall quality of life. It may also stimulate bone gain and decrease bone loss. Its positive effects are an adjunct to other interventions, such as hormonal therapy. It may give patients the confidence to resume regular activity and can provide social interaction and support. During exercise programs, proper nutrition is necessary to prevent excessive weight loss and impaired immune function resulting from inadequate protein, vitamin and mineral intake. Recommendations: Immobilization should be avoided if possible in anyone with osteoporosis or at increased risk for osteoporosis. Regular, moderate physical activity is recommended for those with osteoporosis. Elderly people should be assessed for risk of falling to identify those in greatest need of an exercise program. Community group exercise programs are beneficial. Younger people with osteoporosis also need exercise that will preserve or improve bone mass, muscular strength, endurance and cardiovascular fitness. Weight loss as a result of physical activity should be avoided and adequate intake of protein, vitamins and minerals assured. Because the benefits of physical activity are independent of the effect of other therapies, physical activity is an essential adjunct to appropriate nutrition and other therapies. Validation: These recommendations were developed by the Scientific Advisory Board of the Osteoporosis Society of Canada at its 1995 Consensus Conference. They are in agreement with the position taken on osteoporosis and exercise by the United States Center for Disease Control and Prevention and the American College of Sports Medicine. Sponsors: Sponsors of the 1995 conference included the Dairy Farmers of Canada, Eli Lilly Canada, Inc., Hoffmann-La Roche Canada Ltd., Merck Frosst Canada Inc. and Procter & Gamble Pharmaceuticals Canada Inc.


Treatment of skin aging with topical estrogens

Abstract:
BACKGROUND: The coincidence of climacteric symptoms and the beginning of skin aging suggests that estrogen deficiency may be a common and important factor in the perimenopausal woman. Often hormones have been considered important in endogenous aging of the skin, but their role has not been clearly defined. Therefore, we investigated, whether topical treatment of the skin with estrogen could reverse some of the changes in the aging skin.

MATERIAL AND METHODS: The effects of 0.01% estradiol and 0.3% estriol compounds were compared in 59 preclimacteric women with skim aging symptoms. Monthly determinations of estrodiol (E2), follicle-stimulating hormone (FSH), and prolactin (PRL) were done and the monthly clinical monitoring was supplemented by measurements of skin hydration by corneometry and profilometry. In 10 patients, skin biopsies were taken for immunohistochemical determination of collagen types I and III.

RESULTS: After treatment for 6 months, elasticity and firmness of the skin had markedly improved and the wrinkle depth and pore sizes had decreased by 61 to 100% in both groups. Furthermore, skin moisture had increased and the measurement of wrinkles using skin profilometry, revealed significant, or even highly significant, decreases of wrinkle depth in the estradiol and the estriol groups, respectively. On immunohistochemistry, significant increases of Type III collagen labeling were combined with increased numbers of collagen fibers at the end of the treatment period. As to hormone levels, only those of PRL had increased significantly and no systemic hormonal side effects were noted.


Prevention of preterm birth. Role of daily telephone contact

Abstract:
OBJECTIVE: To compare the effectiveness of routine management of patients at high risk for preterm delivery to the effectiveness of routine management in combination with daily telephone nursing contact.

STUDY DESIGN: The control group, 1 (n = 21), had education and frequent prenatal visits and cervical examinations. The study group, 2 (n = 21), had education, frequent prenatal visits and cervical examination, and daily telephone contact. Group 3 (n = 22) received education but refused to participate.

RESULTS: There were no significant differences (SD) between groups in race, smoking, age, multiple gestation, visits, diagnosis of premature labor, mean days gained after diagnosis of premature labor, tocolytic use or bed rest. There was also no SD in preterm birth rate, mode of delivery, number of maternal or neonatal hospital days, mean neonatal weight or gestational age at delivery between groups. While not reducing the overall incidence of preterm birth, this management for all groups resulted in a more advanced gestational age at the time of delivery (mean change = 7.5 weeks, P < .0001) when compared to the patient's first preterm birth.

CONCLUSION: This study indicated that daily contact, while providing reassurance and support, did not change the outcome when the study group was compared to women managed similarly but without daily contact.


The efficacy of 250 mg/day flutamide in the treatment of patients with hirsutism

Abstract:
OBJECTIVE: To investigate the effects of low dose flutamide (250 mg/d) on hirsutism score and hormone levels in women with hirsutism.

DESIGN: Nonrandomized, prospective clinical trial.

PATIENTS: Forty-one patients with moderate-severe hirsutism were included in the study.

INTERVENTION: Hirsute patients received 250 mg/d flutamide for a period of 6 months.

MAIN OUTCOME MEASURES: Hirsutism score, FSH, LH, E2, total T, free T, androstenedione, DHEAS, PRL, 17-hydroxyprogesterone, and sex hormone-binding globulin levels were detected in all the patients before treatment and every 3 months during treatment.

RESULTS: Treatment with the antiandrogen flutamide resulted in a particularly rapid and marked decrease in the hirsutism score, which decreased from 17.48 +/- 5.35 to 5.07 +/- 2.89 after 6 months. No significant changes in the levels of hormone and no serious side effects were observed in the study.

CONCLUSION: The low-dose flutamide, 250 mg/d, is a cost-effective drug in the treatment of hirsutism. Low-dose flutamide may be used in place of high-dose flutamide, 500 to 750 mg/d.


Oral contraceptives alter circadian rhythm parameters of cortisol, melatonin, blood pressure, heart rate, skin blood flow, transepidermal water loss, and skin amino acids of healthy young women

Abstract: Sixteen healthy women users and nonusers of oral contraceptives (OC) volunteered to document a set of circadian rhythms. Nine were taking OC providing ethynyl estradiol (0.03-0.05 mg/24h, 21 days/month) combined with DL- or L-norgestrel or norethisterone. There was no group difference (p > 0.05) in median age (22 years), weight (57 kg), and height (162) cm). Data were obtained at fixed hours, 5 times/24h, during a 48-h span, in November. (Day activity from approximately 08:00 to approximately 23:00 h and night rest). Environmental conditions were controlled, using air-conditioned rooms of constant temperature (26 degrees +/- 0.5) and relative humidity 45% +/- 1. Both cosinor and ANOVA were used for statistical analyses. All circadian rhythms were validated with one exception: that of salivary melatonin was not detected in OC users. The 24h mean (M) exhibited group differences for certain variables: M was greater in OC than non-OC users for systolic blood pressure (p < 0.0001), heart rate (p < 0.01), skin blood flow (p < 0.04), and transepidermal water loss (p < 0.02). M was lower in OC than non-OC users in salivary cortisol (p < 0.04) and skin amino acids (p < 0.003). No group difference was detected in any other documented rhythms: diastolic blood pressure, grip strength of both hands, oral temperature, self-rated fatigue, and the skin variables of urea, lactate, triglycerides, and acid phosphatase activity.


The significance of transvaginal ultrasonographic evaluation of the cervix in women treated with emergency cerclage

Abstract:
OBJECTIVE: Our purpose was to determine whether perioperative transvaginal ultrasonographic evaluation of the incompetent cervix treated with emergency cerclage is predictive of pregnancy outcome.

STUDY DESIGN: Twenty-nine women who underwent emergency cerclage at 16 to 26 weeks of gestation had transvaginal ultrasonographic evaluation of the cervix within 48 hours before and after surgery and at least three times thereafter until 28 weeks of gestation. The following measurements were obtained: (1) funnel width, (2) funnel length, (3) endocervical canal length, (4) the distance between the internal and external os, (5) upper cervix (length of closed endocervical canal above the cervical cerclage), (6) lower cervix (endocervical canal length below suture), and (7) cervical index (1+ Funnel length/Endocervical canal length). Values are reported as the median in millimeters, and statistical analysis was performed by use of the Mann-Whitney U test, Wilcoxon signed-rank test, Spearman rank correlation, 2 x 2 contingency tables, and multiple regression analysis with significance set at p < 0.05.

RESULTS: Cerclage procedures resulted in significant improvement in postoperative median measurements of funnel width (15 vs 4.0 mm, p < 0.0001), funnel length (29 vs 3 mm, p < 0.0001), and endocervical canal length (2 vs 27 mm, p < 0.0001). There was a significant relationship between gestational age at delivery and the following

measurements: preoperative funnel width (r = -0.51, p = 0.007), postoperative endocervical canal length (r = 0.39, p = 0.04), length of the lower cervix (r = 0.39, p = 0.038), and the cervical index (r = -0.39, p = 0.038). An upper cervical length < 10 mm was a good predictor of delivery before 36 weeks of gestation, sensitivity 85.7% (12/14), specificity 66.7% (10/15), positive predictive value 70.6% (12/17), negative predictive value 83% (10/12), and Fisher's exact p = 0.008. Postoperatively all patients had upper cervical lengths < 10 mm by 28 weeks of gestation. Preoperative digital assessments of cervical dilatation before surgery did not correlate with gestational age at birth (r = -0.031, p = 0.36).

CONCLUSIONS: In cases of cervical incompetence treated with emergency cerclage, perioperative transvaginal ultrasonographic assessment of the cervix reveals that the procedure results in improved ultrasonographic status of the cervix and that the ultrasonographic cervical findings before and after surgery correlate with pregnancy outcome.

American Journal of Obstetrics and Gynecology


Transvaginal ultrasound and preterm prelabor: a nonrandomized intervention study

R W Zalar

Department of Obstetrics and Gynecology, Torrance Memorial Medical Center, California, USA.

Abstract:
OBJECTIVE: To characterize the continuum between normal and preterm labor to prevent spontaneous preterm birth and low birth weight.

METHODS: Between August 1, 1992, and November 30, 1993, obstetric patients from a large managed care medical group were assigned in rotation to five private practice offices for pregnancy care. In the study office (374 births), a systematic approach of visit-by-visit screening, patient education, selective office evaluation of cervical change by transvaginal ultrasound examination, outpatient modification of activity, and graded oral or subcutaneous tocolysis was used; inpatient tocolysis was used only when outpatient management failed. In the comparison offices (1391 births), transvaginal ultrasound was not used and conventional methods were used at the discretion of the attending physicians.

RESULTS: Birth weights below 1500 g (P = .008; odds ratio [OR] 0.08, 95% confidence interval [CI] 0.05-1.32), 2000 g (P = .21; OR 0.21, 95% CI 0.05-0.88), and 2500 g (P = .008; OR 0.44, 95% CI 0.23-0.83) occurred significantly less often in the study group than in the comparison group. The difference in spontaneous preterm births under 2500 g was also significant (P < .001; OR 0.08, 95% CI 0.01-0.58).

CONCLUSION: By emphasizing transvaginal ultrasound and graded outpatient tocolysis, the diagnosis and management of preterm prelabor was associated with a reduction in the rate of spontaneous preterm birth and low birth weight infants.


ACOG technical bulletin. Chronic pelvic pain. Number 223--May 1996 (replaces no. 129, June 1989). American College of Obstetricians and Gynecologists

Committee on Technical Bulletins of the American College of Obstetricians and Gynecologists

Abstract: Although treating patients with chronic pelvic pain may pose a challenge, such patients can often be treated successfully. Effective modalities are available to lessen the impact of the pain and offer the reasonable expectation of return to normal function.

International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics


Menstrual and reproductive factors and hip fractures in post menopausal women

F Parazzini

Mario Negri Institute for Pharmacological Research

Abstract:
Objectives: We analyzed the relationship between menstrual and reproductive history and risk of hip fractures in post-menopausal women using data from an Italian case-control study.

Methods: Cases were 206 post-menopausal women admitted for fractures of the hip proximal femur to a network of teaching and general hospitals in Milan, Italy. The comparison group consisted of 590 post-menopausal women admitted to the same network of hospitals for acute, non-neoplastic, non-hormone-related conditions, other than traumatic or orthopedic disorders. Odds ratios (OR) of hip fracture were derived from unconditional multiple logistic regression.

Results: No relation emerged between risk of hip fractures and age at menarche, lifelong menstrual cycle pattern and age at menopause. In comparison with women with age at menopause > or = 53 years, the multivariate OR of hip fractures were 1.2, 1.1, 1.2 and 0.5 in women with menopause at 50-52, 45-49, 40-44 and before 40 years (X2(1) trend 0.21). In comparison with nulliparae, the estimated age-adjusted OR was 0.6 (95% confidence interval, CI, 0.4-0.9) for parous women, but the multivariate estimate was not significant (OR 0.8, 95% CI 0.6-1.3) and the multivariate trend in risk with number of births was not significant either. No relation emerged between hip fractures and age at first and last birth, and history of abortions.

Conclusions: This study found no relevant influence of menstrual and reproductive factors on the risk of hip fractures in post-menopausal women. However, this is not in contrast with the observation of a short-term effect of menopause and more in general. female hormone levels on osteoporosis and hence on hip fractures.


Effect of estriol on bone loss in postmenopausal Japanese women: a multicenter prospective open study

Abstract:
OBJECTIVES: To assess the effects of oral estriol on the bone mineral density (BMD) and bone metabolism in postmenopausal women.

METHODS: Seventy-five natural postmenopausal women with a BMD of more than 10% below the peak bone density were treated for 50 weeks with 2 mg/day estriol (E3) cyclically and 0.8 g/day of calcium lactate continuously. BMDs at L2-L4 were measured by dual energy X-ray absorptiometry (DXA).

RESULTS: The BMD increased 1.79% (p < 0.01 vs. pretreatment) after 50 weeks, accompanied with decrease of biochemical markers of bone turnover. With regard to climacteric symptoms, Kupperman's menopausal index improved (p < 0.01 vs. pretreatment) after 5 weeks of treatment. As to the incidence of adverse events genital bleeding was observed in only 8.0% of the subjects. Endometrial histology and cytology showed neither abnormalities nor hyperplasia during and after the treatment.

CONCLUSIONS: Estriol prevented postmenopausal bone loss and improved climacteric symptoms effectively with low incidence of genital bleeding.

The Journal of Obstetrics and Gynaecology Research


Risk factors, falls, and fracture of the distal forearm in Manchester, UK

Terence W O'Neill

ARC Epidemiology Research Unit, Manchester University.

Abstract:
Objective: To determine the risk factors associated with fracture of the distal forearm, and to evaluate the influence of falls on these risks.
Design: This was a case-control study.
Setting: Manchester, UK.

Participants: The cases were 62 white women aged 45-82 years who had sustained a fracture of the distal forearm and had attended local hospitals. Two control groups were studied - 50 women who had fallen onto the hand but had not sustained a fracture (recruited from the same source as those with fracture) and 116 women randomly selected from primary care age and sex registers in the catchment area of the hospitals. Both cases and controls were sent a letter inviting them to take part in the study. Data were collected by questionnaire completed by an interviewer.

MAIN Results: Compared with the population control group, those with fracture were more likely to walk at a brisk pace (odds ratio (OR) = 3.5; 95% confidence interval (CI) 1.3, 9.6) though they had undertaken less physical activity at home or work on a daily basis throughout life (OR = 0.4; 95% CI 0.2, 0.9). The risk associated with brisk walking was less marked when the cases were compared with fall controls. Other lifestyle factors including calcium intake, smoking, and alcohol consumption were not associated with fracture. Analysis of gynaecological and hormonal factors suggested that compared with population controls, those with fracture of the distal forearm had had fewer fertile years (OR = 0.4; 95% CI 0.1, 0.9) and were less likely to have used oral contraceptives (OR = 0.3; 95% CI 0.1, 0.9).

Conclusions: The data highlight the need for caution when advising middle aged and elderly subjects about exercise. Such advice should be combined with practical information about the prevention of falls. Hormonal factors seem to be additional determinants of fracture. Other lifestyle interventions seem unlikely to play an important part in preventing distal forearm fracture.

Journal of Epidemiology and Community Health


Changes in muscle strength, relaxation rate and fatiguability during the human menstrual cycle

Abstract: 1. The effect of the different phases of the menstrual cycle on skeletal muscle strength, contractile properties and fatiguability was investigated in ten young, healthy females. Results were compared with a similar group on the combined (non-phasic) oral contraceptive pill (OC). Cycle phases were divided into the early and mid-follicular, mid-cycle (ovulatory) and mid- and late luteal. Cycle phases were estimated from the first day of the menstrual bleed. 2. Subjects were studied weekly through two complete cycles. Measurements included quadriceps and handgrip maximum voluntary isometric force and the relaxation times, force-frequency relationship and fatigue index of the quadriceps during percutaneous stimulation at a range of frequencies from 1 to 100 Hz. 3. In the women not taking the OC there was a significant increase of about 11% in quadriceps and handgrip strength at mid-cycle compared with both the follicular and luteal phases. Accompanying the increases in strength there was a significant slowing of relaxation and increase in fatiguability at mid-cycle. No changes in any parameter were found in the women taking the OC. 4. The changes in muscle function at mid-cycle may be due to the increase in oestrogen that occurs prior to ovulation.


Pregnancy and the timing of intercourse

Pregnancy and the timing of intercourse

Thomas W Hilgers

Pope Paul VI Institute for the Study of Human Reproduction, Omaha, Nebraska.

Abstract: The optimal timing of sexual intercourse in relation to the day of ovulation in order for pregnancy to result is a topic of broad interest. Of obvious relevance to fecundability, on the one hand, a...


Hypothalamic corticotropin-releasing hormone suppression during the postpartum period: implications for the increase in psychiatric manifestations at this time

Douglas S. Rabin

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Abstract: The third trimester of human pregnancy is characterized by a hyperactive hypothalamic-pituitary-adrenal axis, possibly driven by progressively increasing circulating levels of placental CRH and gradually decreasing levels of CRH-binding protein. The postpartum period, on the other hand, is characterized by an increased vulnerability to psychiatric manifestations (postpartum "blues," depression, and psychosis), a phenomenon compatible with suppressed hypothalamic CRH secretion. To investigate the hypothesis that the postpartum period is associated with suppression of hypothalamic CRH secretion, we studied prospectively 17 healthy euthymic women (mean +/- SE age, 32.0 +/- 1.1 yr) with no prior history of depression, starting at the 20th week of gestation. Psychometric testing was performed monthly during pregnancy and postpartum on day 2 and weeks 2, 3, 6, 8, 12, 16, and 20, whereas serial ovine (o) CRH tests were performed postpartum at 3, 6, and 12 weeks. While pregnant, all 17 subjects remained euthymic; in the postpartum period, 7 women developed the "blues," and 1 developed depression. Overall, the mean plasma ACTH response to an iv bolus of 1 microgram/kg oCRH was markedly blunted at 3 and 6 weeks, but normal at 12 weeks postpartum, whereas the mean plasma cortisol response was at the upper limit of normal at all 3 times. These data are compatible with a suppressed hypothalamic CRH neuron that gradually returns to normal while hypertropic adrenal cortexes are progressively down-sizing. When the postpartum ACTH responses to oCRH were analyzed separately for the euthymic women and the women who had the "blues" or depression, the blunting of ACTH was significantly more severe and long lasting in the latter group; this was observed at all 3 times of testing. We conclude that there is central suppression of hypothalamic CRH secretion in the postpartum, which might explain the increased vulnerability to the affective disorders observed during this period. The suppressed ACTH response to oCRH might serve as a biochemical marker of the postpartum "blues" or depression.

The Journal of Clinical Endocrinology and Metabolism


The preterm prediction study: fetal fibronectin testing and spontaneous preterm birth. NICHD Maternal Fetal Medicine Units Network

Brian Mercer

From Wake Forest University, Winston-Salem, N.C. (P.J.M.); the National Institute of
          Child Health and Human Development, Bethesda, Md. (M.K., C.Y.S.); the Biostatistics
          Center, ...

Abstract:
OBJECTIVE: To evaluate the presence of fetal fibronectin in the cervix and vagina as a screening test for spontaneous preterm birth.

METHODS: Two thousand nine hundred twenty-nine women at ten centers were routinely screened every 2 weeks from 22-24 to 30 weeks for cervical and vaginal fetal fibronectin. A positive test was defined as a value equal to or greater than 50 ng/mL. The relation between a positive test at four gestational ages and spontaneous preterm birth at various intervals after the test was determined.

RESULTS: In each testing period, 3-4% of the fetal fibronectin tests were positive. The correlation between cervical and vaginal fetal fibronectin at the same visit was always approximately 0.7 (P < .001), and that between cervical or vaginal fetal fibronectin in consecutive visits was between 0.17 and 0.25 (P < .001). The sensitivity of fetal fibronectin at 22-24 weeks to predict spontaneous preterm birth at less than 28 weeks was 0.63, and the relative risk for a positive versus negative test was 59. The specificity was always 96-98%, whereas the positive predictive value rose from 13% to 36% as the upper limit of the definition of preterm birth was increased from less than 28 to less than 37 weeks. The relative risk for spontaneous preterm birth after a positive fetal fibronectin test compared with a negative fetal fibronectin test varied substantially by testing period and by the definition of spontaneous preterm birth, but always remained greater than 4 and statistically significant.

CONCLUSION: A positive cervical or vaginal fetal fibronectin test at 22-24 weeks predicted more than half of the spontaneous preterm births at less than 28 weeks (sensitivity 0.63). As the definition of spontaneous preterm birth was extended to include later gestational ages or when the fetal fibronectin test was performed later in pregnancy, the level of association between a positive fetal fibronectin test and spontaneous preterm birth, while remaining highly significant, tended to decrease. Although fetal fibronectin is an excellent test for predicting spontaneous preterm birth, we present no evidence that the use of this test will result in a reduction in spontaneous preterm birth.


Effect of oral estradiol on Lp(a) and other lipoproteins in postmenopausal women. A randomized, double-blind, placebo-controlled, crossover study

Abstract:
BACKGROUND: Lp(a) lipoprotein level is an independent risk factor for premature coronary artery disease and cerebrovascular accident. Concentrations of this lipoprotein tend to increase after menopause.

OBJECTIVE: To determine whether oral estrogen was effective in lowering concentrations of Lp(a) lipoprotein in postmenopausal women.

METHODS: A double-blind, placebo-controlled, cross-over study was conducted during a 12-month period in 100 postmenopausal women who had undergone hysterectomy. They were randomized into two groups: group 1 received oral estradiol, 2 mg/d, for the first 6 months and placebo for the second, and group 2 received these treatments in the reverse order. After completion of the crossover study, the effect of prolonged administration of oral estradiol was examined by placing all patients on active treatment and repeating the lipoprotein measurements approximately 12 months later.

RESULTS: No significant differences were noted between the two groups at the commencement of the study (median concentration of Lp[a] lipoprotein, 10.78 mg/dL [range, 2.2 to 108.5 mg/dL] in group 1 and 12.74 mg/dL [range, 0.8 to 98.1 mg/dL] in group 2). Crossover analysis showed a 9.62% reduction in values of Lp(a) lipoprotein with estradiol treatment compared with placebo during 12 months of treatment (P < .001). With prolonged treatment, the median concentration of Lp(a) lipoprotein for those in group 1 decreased from 8.12 mg/dL (range, 1.05 to 57.4 mg/dL) to 5.77 mg/dL (range, 0.84 to 75.39 mg/dL) (P < .001). In group 2, the median concentration decreased from 8.19 mg/dL (range, 2.52 to 99.82 mg/dL) to 7.07 mg/dL (range, 0.70 to 48.79 mg/dL), but this difference was not significant (P = .63).

CONCLUSIONS: The results of this study confirm the beneficial effect of oral estradiol on the basic lipoprotein pattern and demonstrate that this treatment is effective in reducing concentrations of Lp(a) lipoprotein in postmenopausal women.


Transdermal oestrogen for treatment of severe postnatal depression

Abstract:
BACKGROUND: Postnatal depression can have long-term adverse consequences for the mother, for the marital relationship, and for the infant's psychological development. Such depressions can be severe and resistant to both support and counselling and to therapy with antidepressant drugs. We investigated the antidepressant efficacy of oestrogen given transdermally.

METHODS: In a double-blind, placebo-controlled study, 61 women with major depression, which began within 3 months of childbirth and persisted for up to 18 months postnatally, were allocated randomly active treatment (n=34; 3 months of transdermal 17 beta-oestradiol 200 micrograms daily alone, then 3 months with added cyclical dydrogesterone 10mg daily for 12 days each month) or placebo (n=27; placebo patches and tablets according to the same regimen). The women were assessed monthly by self-ratings of depressive symptoms on the Edinburgh postnatal depression scale (EPDS) and by clinical psychiatric interview (schedule for affective disorders and schizophrenia [SADS]-change scale).

FINDINGS: On pretreatment assessments the women in both groups were severely depressed (mean EPDS score 21.8 [SD 3.0] active group, 21.3 [2.9] placebo group; SADS scores, 66.3 [11.4] and 64.3 [10.7]). During the first month of therapy the women receiving oestrogen improved rapidly, and to a significantly greater extent than controls (mean EPDS scores 13.3 [SD 5.7] vs 16.5 [5.3]. Patients receiving placebo also improved over time but, on average, their scores did not fall below the screening threshold for major depression for at least 4 months. The estimated overall treatment effect of oestrogen on the EPDS was 4.38 points (95% Cl 1.89-6.87). None of a range of other factors (age, psychiatric, obstetric and gynaecological history, severity and duration of current episode of depression, and concurrent antidepressant medication), influenced the response to oestrogen.

INTERPRETATION: This study has shown that transdermal oestrogen is an effective treatment for postnatal depression. Further studies are required to establish the minimum effective dose and shortest necessary duration of treatment as well as the mechanism of antidepressant action of oestrogen.


Delay in the diagnosis of endometriosis: a survey of women from the USA and the  UK

Abstract: We investigated the length of time between the onset of pain symptoms and the surgical diagnosis of endometriosis in women from the UK and the USA. A total of 218 women with surgically confirmed disease, recruited through endometriosis self-help groups, completed a postal questionnaire. The mean +/- SD delay in diagnosis for women from the USA was 11.73 +/- 9.05 years, significantly higher than the equivalent delay of 7.96 +/- 7.92 years for women from the UK (P < 0.01). The stage of disease did not effect the length of time between the onset of symptoms and diagnosis. Therefore there is considerable delay in the diagnosis of endometriosis for women from both the UK and the USA. Efforts to reduce this delay are required to minimize the suffering of women with this disease.


Donor insemination: a comparison of lesbian couples, heterosexual couples and single women

Abstract:
OBJECTIVE: To compare single women, lesbian couples, and heterosexual couples receiving therapeutic donor insemination (TDI).

DESIGN: Chart review followed by anonymous mail questionnaires to donor insemination recipients and their partners.

SETTING: Infertility clinic in a university hospital.

PATIENTS: One hundred fifteen women receiving donor insemination were identified by chart review.

RESULTS: Too few single women responded for reliable comparison. Lesbian women were similar to married women in age, education, duration, and outcome of donor insemination. When considering alternatives to TDI, married women were more likely to consider adoption and lesbians were most likely to consider using a known semen donor or having intercourse with a man aware of their desire to have a child. Married couples were less likely to tell others, including the child, about conception by donor insemination. They were also less likely to support disclosing identifying data about the donor to the child. Lesbians were more likely to report stress in their relationships as a result of TDI. Married men were most likely to support mandatory counseling before TDI initiation.


Clomiphene citrate with intrauterine insemination: is it effective therapy in women above the age of 35 years?

Abstract:
OBJECTIVES: To evaluate the influence of female age on clomiphene citrate (CC) with IUI therapy and to compare the efficacy of this therapy between patients with ovulatory and anovulatory infertility.

SETTING: A university fertility clinic.

SUBJECTS: Six hundred sixty-four CC with IUI cycles from 290 women aged 22 to 48 years.

MAIN OUTCOME MEASURES: Cumulative and clinical pregnancy rates (PRs).

RESULTS: Both cumulative and clinical PRs declined substantially in women > 35 years when compared with those < or = 35 years. In addition, no difference in these parameters was noted between patients with ovulatory and anovulatory infertility diagnoses. The vast majority of pregnancies occurred within the first four treatment cycles, irrespective of age or ovulatory versus anovulatory infertility diagnoses.

CONCLUSIONS: The age-related decline in clinical PR is most rapid beginning at the age of 35 years. For any given age group, CC with IUI therapy has similar cumulative and clinical PRs for both ovulatory and anovulatory infertility diagnoses. This therapy usually should not extend beyond four cycles. Couples should be counseled about the dramatic fall in PRs occurring beyond the age of 35 years.


Breast and Ovarian Cancer Incidence after Infertility and In Vitro Fertilization


Scientific bases for NFP beyond question

Abstract: The Couple to Couple League (CCL) is pleased that an article and an editorial in the December 1995 issue of the well-respected New England Journal of Medicine confirm that natural family planning (NFP) has value and is scientifically based, a fact the CCL has known for many years. The research covered in the article entitled Timing of Sexual Intercourse in Relation to Ovulation found that the only fertile days were the five days before ovulation and the day of ovulation itself. Most conceptions (76.4%) occurred during the day of and the first and second days before ovulation. CCL's slide showing the extent of the fertile time reflects the data of the report, but also includes the possibility of a second ovulation occurring within 24 hours of the first ovulation. The study found that women conceived in only 37% of cycles in which intercourse took place during the six-day fertile period. This rate is not much different than that claimed by a NFP physician many years ago (about 30%). The study showed the highest conception probability to be when the couple had sexual intercourse every day during the fertile period (37% vs. 33% for every other day). CCL advises couples to abstain until the fertile period then follow one coital frequency period during one cycle (e.g., every day) and the other pattern the next cycle (e.g., every other day). The study refuted claims that the timing of coitus relative to ovulation was not associated to the sex of the baby and that aging sperm do not reduce the viability of the fetus and/or cause birth defects. In fact, aging sperm rarely fertilize the ovum. The only way to positively detect ovulation is seeing the ovum burst out of the ovary. Hormone analyses of blood or urine and observations of cervical mucus and basal body temperature allow an estimate of the day of ovulation. NFP is not based on detecting ovulation but on identifying the limits of the fertile period.


Ovulatory premenopausal women lose cancellous spinal bone: a five year prospective study

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract: Healthy premenopausal women with regular cycles are believed to be increasing or maintaining bone density. However, few studies have prospectively documented spinal cancellous bone, the bone that changes rapidly in response to reproductive hormones, in this population. Furthermore, our previous one-year study documented that 24% of the one-year bone change by quantitative computed tomography (QCT) was related to subclinical ovulatory disturbances (short luteal phase and non-ovulation) in the presence of regular menstrual cycles. The purpose of this study was to document the cancellous bone change over five years in this initially ovulatory, premenopausal cohort of 66 healthy women. Thirty-seven women, who continued to be premenopausal and have regular cycles, completed this five-year study. Those enrolled differed only by being older and weighing less than those who could not be contacted (n = 19) or who declined to participate (n = 10). Documentation of current ovulatory characteristics was obtained for at least three cycles in 27 women. At the five-year assessment, the volunteers were 40.6 (range 26-47) years old, weighed 58.5 (41-77) kg, and were 160.9 (149-174) cm in height. All were premenopausal, healthy, nonsmokers with regular menstrual cycles (mean 27.7, range 24-33 days). Six women with intervening events (such as pregnancy or use of oral contraceptives) had interval (12 to 60 months) QCT changes similar to the remaining 31 (-7.98 vs. -4.92 mg/cm, p = 0.1, respectively). Mean five-year QCT was 143.0 +/- 20.2 mg/cm, whereas the initial mean value was 151.9 +/- 20.1 mg/cm. Significant QCT loss over five years (-8.9 +/- 6.2 mg/cm) (95% Cl -6.9 to -11.0) correlated with QCT change in the first year (r = 0.629, p < 0.001). First-year change was not related to the subsequent four-year interval change (r = -0.056, p = 0.74), however. Five-year QCT change was not related to age, weight, osteoporosis family history, estimated calcium intake, or exercise, but did correlate with year one luteal index (luteal/cycle length) (r = 0.339, p = 0.043). Significant cancellous spinal bone loss occurs in healthy, ovulatory premenopausal women, and is influenced by subclinical disturbances of ovulation.


Reproductive aging: accelerated ovarian follicular development associated with a monotropic follicle-stimulating hormone rise in normal older women

W J Bremner

United States Department of Veterans Affairs

Abstract: Women experience a decline in fertility that precedes the menopause by several years. Previous studies have demonstrated a monotropic rise in FSH associated with reproductive aging: however, the mechanism of this rise and its role in the aging process are poorly understood. The purpose of this study was to characterize ovarian follicular development and ovarian hormone secretion in older reproductive age women. Sixteen women, aged 40-45 yr, with regular ovulatory cycles were studied. The control group consisted of 12 ovulatory women, aged 20-25 yr. Serum obtained by daily blood sampling was analyzed for FSH, LH, estradiol (E), progesterone, and inhibin (Monash polyclonal assay). Follicle growth and ovulation were documented by transvaginal ultrasound. Older women had significantly higher levels of FSH throughout the menstrual cycle. E, progesterone, LH, and inhibin levels did not differ between the two age groups when compared relative to the day of the LH surge. Ultrasound revealed normal growth, size, and collapse of a dominant follicle in all subjects. Older women had significantly shorter follicular phase length associated with an early acute rise in follicular phase E, reflecting accelerated development of a dominant follicle. We conclude that older reproductive age women have accelerated development of a dominant follicle in the presence of the monotropic FSH rise. This is manifested as a shortened follicular phase and elevated follicular phase E. The fact that ovarian steroid and inhibin secretion were similar to those in the younger women suggests that elevated FSH in women of advanced reproductive age may represent a primary neuroendocrine change associated with reproductive aging.

The Journal of clinical endocrinology and metabolism


A prospective controlled study of luteal and endometrial abnormalities in an infertile population

L K Nieman

Health and Human Development (2HD) Research Network

Abstract:
OBJECTIVE: To investigate whether luteal and endometrial abnormalities occur more frequently in an infertile population and thus contribute to infertility.

DESIGN: Prospective controlled clinical study.

SETTING: Outpatient clinic in an academic research institution.

PARTICIPANTS: Thirty-three fertile controls and 31 infertile women without ovulatory disorders, tubal disease, or male factors.

INTERVENTIONS: All women underwent an endometrial biopsy 9 days after the LH surge followed by an IM injection of 5,000 IU hCG. Blood samples were drawn immediately before hCG administration for serum P and placental protein 14 (PP14) measurements, at 6 hours after hCG stimulation for serum P concentrations, and on day 5 after hCG administration for serum PP14 levels.

MAIN OUTCOME MEASURES: Histologic dating of the endometrium and serum P and PP14 measurements.

RESULTS: Abnormal endometrial biopsies occurred more frequently in infertile (43%) than in fertile women (9%). Except for one case, these specimens were not associated with low hCG-stimulated P levels. Serum PP14 measurements varied widely and did not discriminate subjects with abnormal endometrial development.

CONCLUSIONS: Disruption of endometrial maturation without a concomitant defect of the corpus luteum occurs more frequently in an infertile population and thus may contribute to infertility.


Relationship between symptom severity and steroid variation in women with premenstrual syndrome: study on serum pregnenolone, pregnenolone sulfate, 5 alpha-pregnane-3,20-dione and 3 alpha-hydroxy-5 alpha-pregnan-20-one

Abstract: The relationship between symptoms of premenstrual syndrome (PMS) and serum levels of pregnenolone (Pe), pregnenolone sulfate (PS), 5 alpha-pregnane-3,20-dione (5 alpha-DHP), 3 alpha-hydroxy-5 alpha- pregnan-20-one (5 alpha-THP), LH, 17 beta-estradiol (E2), and progesterone (P) was investigated during 2 consecutive menstrual cycles in 12 patients using daily measurements. Corresponding hormones were also measured during 1 cycle in 8 control women. Pe, PS, 5 alpha-DHP, and 5 alpha-THP showed a significant cyclicity within menstrual cycles and a high rate of correlation with P variation in both PMS patients and controls. No significant difference was found between PMS patients and controls in average serum concentrations of Pe, PS, 5 alpha-DHP, 5 alpha-THP, and LH during the luteal phase, whereas a significantly higher level of E2 and a lower level of P were observed in PMS patients. The variation in symptom scores was compared with that in hormone levels within each woman. The symptom peak showed a delay of 3-4 days after the serum P, Pe, 5 alpha-DHP, and 5 alpha-THP peaks. However, the plasma PS peak appeared on the same day or only 1 day before the symptom peak in PMS patients. When comparing the 2 cycles studied, more negative symptoms occurred in cycles with higher luteal phase E2, Pe, and PS concentrations, whereas higher luteal phase 5 alpha-DHP and 5 alpha-THP concentrations were associated with improved symptom ratings in PMS patients. These results suggest that the mentioned steroids are related to the severity of distressing symptoms in PMS patients.

The Journal of Clinical Endocrinology and Metabolism