The ubiquitousness of premenstrual tension in gynecologic practice

Diagnosis and treatment of premenstrual syndrome

Abraham GE et al., 1990 · Fertil Steril

Absorption of oral progesterone is influenced by vehicle and particle size

Hargrove JT et al., 1989 · Am J Obstet Gynecol

The oral route of progesterone administration has long been considered impractical because of poor absorption and short biologic half-life. Recent reports suggest that micronization of progesterone enhances absorption and increases serum and tissue levels of progesterone. This study checks serum progesterone levels before and 0.5, 1, 2, 3, 4, and 6 hours after oral administration of 200 mg of progesterone in seven subjects. Progesterone was plain milled, micronized, plain milled in oil, micronized in oil, or micronized in enteric-coated capsules. All patients exhibited a significant increase in serum progesterone levels after oral progesterone administration. Mean peak progesterone levels (30.3 +/- 7.0 ng/ml) (p less than 0.005) were achieved with micronized progesterone in oil at 2.0 +/- 0.3 (p less than 0.05) hours after administration. Four types of oral progesterone had equivalent mean peak elevations and mean times to peak: plain milled, 9.6 +/- 2.5 ng/ml at 4.0 +/- 0.5 hours; micronized 13.2 +/- 2.4 ng/ml at 3.2 +/- 0.4 hours; plain milled in oil, 11.3 +/- 3.0 ng/ml at 4.0 +/- 0.5 hours; and micronized in enteric-coated capsules, 11.2 +/- 3.0 ng/ml at 4.1 +/- 0.7 hours. Contrary to traditional teaching, these data show that significant serum progesterone levels can be achieved by oral administration. Absorption can be significantly improved by the physical characteristics of the progesterone and the vehicle used with oral administration.

Sedative and hypnotic effects of oral administration of micronized progesterone may be mediated through its metabolites

Arafat ES et al., 1988 · Am J Obstet Gynecol

Progesterone and its metabolites were measured in serum extracts by radioimmunoassay and gas chromatography-mass spectrometry, respectively, after ingestion of micronized progesterone by eight postmenopausal women. One subject received 400 mg of micronized progesterone orally that induced a hypnotic state that lasted for approximately 2 hours. Blood samples were drawn periodically from all subjects for measurement of progesterone and its metabolites in serum. Levels of serum progesterone and its metabolites increased significantly from baseline values and reached a peak between 2 and 6 hours after oral progesterone administration. Significant quantities of five compounds (progesterone, 5 alpha-pregnan-3 alpha-ol-20-one, 5 beta-pregnan-3 alpha-ol-20-one, 5 beta-pregnan-3 alpha,20 beta-diol, and 5 beta-pregnan-3 alpha-ol-11,20-dione) that have been reported to possess anesthetic qualities were identified. The sedative and hypnotic effects of oral administration of progesterone may be mediated through those compounds.

Bioavailability of oral micronized progesterone

Maxson WS et al., 1985 · Fertil Steril

Progesterone (P) has not been administered orally because of reportedly poor bioavailability and a rapid clearance rate. Unfortunately, the synthetic derivatives, although orally active, have a number of disadvantages and fail to mimic natural P completely. To investigate the bioavailability and short-term toxicity of oral micronized P, a standardized dose of 200 mg of micronized P was administered to nine healthy postmenopausal women and one male subject. Serial determinations of serum P concentrations demonstrated rapid absorption of P. Peak concentrations of P rose from a negligible baseline level to 17.0 +/- 4.9 ng/ml at an average of 2.8 +/- 0.35 hours after administration. The peak concentrations of P were equivalent to those observed in the midluteal phase in normal control cycles (14.1 +/- 2.7 ng/ml). All subjects exhibited significant elevation of P over baseline levels that persisted for at least 6 hours after the single oral dose and returned to initial levels by 24 hours. There was no significant change in estradiol, follicle-stimulating hormone, luteinizing hormone, cortisol, aldosterone, lipids, or hepatic enzymes during the 24-hour study interval.

Severity of premenstrual symptoms in a health maintenance organization population

Sternfeld B et al., 2002 · Obstet Gynecol

To describe severity of emotional and physical symptoms in a large diverse sample; to examine demographic, health status, and behavioral correlates of symptom severity; and to describe use of medications and alternative remedies for premenstrual symptoms. A total of 1194 women, ages 21-45, selected from members of a large northern California health maintenance organization, completed daily ratings of symptom severity for two menstrual cycles. An empirically derived algorithm defined symptom severity groups as minimal (n = 186), moderate (n = 801), severe (n = 151), or premenstrual dysphoric disorder (n = 56). Symptom severity as a continuous variable was defined by the two-cycle mean symptom ratings in the luteal phase. Demographic, health status, and behavioral factors and use of treatments for premenstrual symptoms were assessed by self-report. Luteal phase symptom-specific ratings were generally significantly greater in the premenstrual dysphoric disorder group than in the other groups (P <.001). Symptom severity score increased with each comorbidity and decreased with each year of age. Symptom severity was also inversely associated with oral contraceptive use (emotional symptoms) and better perceived health (physical symptoms). Hispanics reported greater severity of symptoms, and Asians less, relative to whites. Use of herbal and nutritional supplements for premenstrual symptoms steadily increased from 10.8% in the minimal group to 30.4% in the premenstrual dysphoric disorder group (P <.01). The degree of premenstrual symptom severity varies in the population, is relatively constant within each woman over two consecutive cycles, particularly for emotional symptoms, and is influenced by age, race/ethnicity, and health status.

Lowered Plasma Steady-State Levels of Progesterone Combined With Declining Progesterone Levels During the Luteal Phase Predict Peri-Menstrual Syndrome and Its Major Subdomains

Roomruangwong C et al., 2019 · Frontiers in Psychology · Free full text on PubMed Central

It is unknown whether lowered steady state levels of sex hormones coupled with changes in those hormones during the menstrual cycle are associated with premenstrual syndrome (PMS). To examine associations between levels of progesterone and oestradiol during the menstrual cycle and PMS considering different diagnostic criteria for PMS. Forty-one women aged 18-45 years with a regular menstrual cycle completed the Daily Record of Severity of Problems (DRSP) for all 28 consecutive days of the menstrual cycle. Blood was sampled at days 7, 14, 21, and 28 to assay oestradiol and progesterone. We developed a new diagnosis of peri-menstrual syndrome, which is characterized by increased DRSP severity in pre and post-menstrual periods and increased scores on the major DRSP dimensions, i.e., depression, physio-somatic symptoms, breast tenderness and appetite, and anxiety. This new diagnosis performed better than classical diagnoses of PMS, including that of the American College of Obstetricians and Gynecologists (ACOG). Lowered steady state levels of progesterone, when averaged over the menstrual cycle, together with declining progesterone levels during the luteal phase predict severity of peri-menstrual symptoms. Steady state levels of oestradiol and declining oestradiol levels during the cycle are also related to DRSP severity although most of these effects appeared to be mediated by progesterone. A significant increase in menstrual-cycle related symptoms can best be conceptualized as "peri-menstrual syndrome" and may result from insufficient progesterone production (relative corpus luteum insufficiency), which, in part may result from lowered oestradiol production indicating suboptimal pre-ovulatory follicular development.

THE HORMONAL CAUSES OF PREMENSTRUAL TENSION

Frank RT, 1931 · Arch NeurPsych

My attention has been increasingly directed to a large group of women who are handicapped by premenstrual disturbances of manifold nature. It is well known that normal women suffer varying degrees of discomfort preceding the onset of menstruation. Employers of labor take cognizance of this fact and make provision for the temporary care of their employees. These minor disturbances include increased fatigability, irritability, lack of concentration and attacks of pain. In another group of patients, the symptoms complained of are of sufficient gravity to require rest in bed for one or two days. In this group, particularly, pain plays the predominant rôle. There is still another class of patients in whom grave systemic disorders manifest themselves predominantly during the premenstrual period. REPORT OF CASESCase 1. —A young, unmarried woman suffered from frequent convulsive attacks, which later occurred exclusively within ten days preceding menstruation. Neurologic investigation resulted in a diagnosis

Hormonal studies in women with premenstrual tension

Watts JF et al., 1985 · Br J Obstet Gynaecol

Serum hormone concentrations were determined at intervals during the last 17 days of the menstrual cycle in 35 patients with premenstrual tension (PMT) and 11 control subjects without symptoms. The maximum mean concentration of oestradiol occurred 17 days before menstruation in the patients and 14 days before in the controls. The maximum concentrations of progesterone were similar in the two groups but the mean concentrations rose earlier in the cycle in the patients with PMT. These results suggested that the patients tended to ovulate earlier in the cycle than the controls and on the basis of the ovulatory surge in gonadotrophins two groups could be identified, group A who showed signs of ovulation 14 days or less before menstruation (17 patients, 9 controls) and group B who ovulated more than 14 days before menstruation (18 patients, 2 controls). There were no significant differences between the groups in prolactin, thyroid stimulating hormone or testosterone levels, but cortisol concentrations were uniformly higher in both groups of patients compared with those in the controls. Follicular growth was assessed with ultrasound in 18 patients and 16 control subjects. Mean follicular diameters were significantly lower in the patients than in the control group at the time of ovulation. Oestradiol determinations done at the same time correlated with the diameters and were also significantly lower in the patient group. The results suggest that ovulation tends to occur prematurely in women with PMT.