Cowan, L. D., Gordis, L., Tonascia, J. A., & Jones, G. S. (1981). Breast cancer incidence in women with a history of progesterone deficiency. American journal of epidemiology, 114(2), 209-217. https://doi.org/10.1093/oxfordjournals.aje.a113184
Cowan LD, Gordis L, Tonascia JA, Jones GS. Breast cancer incidence in women with a history of progesterone deficiency. Am J Epidemiol. 1981;114(2):209-217. doi:10.1093/oxfordjournals.aje.a113184
Cowan, L. D., et al. "Breast cancer incidence in women with a history of progesterone deficiency." American journal of epidemiology, vol. 114, no. 2, 1981, pp. 209-217.
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In order to investigate the nature of the association of involuntarily delayed first birth and risk of breast cancer, 1083 white women who had been evaluated and treated for infertility from 1945-1965 were followed prospectively through April 1978 to ascertain their breast cancer incidence. These women were categorized as to the cause of infertility into two groups, those with endogenous progesterone deficiency (PD) and those with nonhormonal causes (NH). Women in the PD group had 5.4 times the risk of premenopausal breast cancer compared to women in the NH group. This excess risk could not be explained by differences between the two groups in ages at menarche or menopause, history of oral contraceptive use, history of benign breast disease or age at first birth. Women in the PD group also experienced a 10-fold increase in deaths from all malignant neoplasms compared to the NH group. The incidence of postmenopausal breast cancer did not differ significantly between the two groups.
The associations between oral contraceptive (OC) use, bone mineral density (BMD) and the risk of fractures remain controversial. A cross-sectional study of 491 women aged 50-80 years was performed. We assessed OC use and fractures by questionnaire, and BMD and vertebral deformity by dual-energy x-ray absorptiometry. Ever use of OC was associated with significantly higher BMD at the total body (6%, p<.001) and spine (4%; p=.05) (but not hip) after adjustment for confounders. There was also a significant association between duration of OC use and total body and spine BMD. Use of OCs for 5-10 years was associated with reduced vertebral deformity (adjusted odds ratio 0.46, 95% confidence interval 0.22-0.94). Oral contraceptive use and duration were associated with higher total body and spine BMD and a consistent reduction in vertebral deformities, although most associations did not reach significance.
This report presents the outcome of pregnancies of 93 women who conceived while taking progesterone (P) suppositories (n = 42) or P in oil intramuscularly (n = 51). The dosage and duration of treatment varied according to the indication. The total dose (in milligrams) increased with the duration of treatment and ranged from 75 to 13,500 mg. Two of 75 term pregnancies (2.6%) were noted to have congenital anomalies. Both women had been treated with P in oil. No patient treated with P suppositories gave birth to a malformed infant. An increased spontaneous abortion rate (28.6%) was noted among women treated with P suppositories. The authors recommend that a national registry be created to document fetal outcome after P therapy.
Fertility following bilateral ovarian wedge resection (BOWR) was evaluated in a retrospective cohort study of 90 consecutive cases of the polycystic ovary syndrome. Post-BOWR follow-up was available for varying time spans of up to 10 years. BOWR resulted in the resumption of menstrual cyclicity in 91.1% (82/90) of the cases. However, within this ovulatory group, 26 patients were characterized by oligo-ovulation and a significantly reduced conception rate (29.2%), as compared with that of 56 normo-ovulatory counterparts (60.3%). Although the crude overall conception rate for this series was 47.8%, the overall cumulative probability of conception at the end of follow-up as determined by life table analysis was 73%. The likelihood of conception at any given point in time was estimated by a monthly fecundability rate of 1.34%. Our findings also indicate that the probability of post-BOWR conception was unaffected by age, race, ward status, or duration of infertility. In contrast, persistent post-BOWR oligo- or anovulation and the presence of concurrent tuboperitoneal disease were reaffirmed as the most important determinants of the likelihood of post-BOWR conception. A minimum incidence of 7.8% was documented for acquired post-BOWR pelvic disease.
The experience of the gynecologic endocrinology and infertility clinic at The Johns Hopkins Hospital has been subjected to a nonconcurrent prospective analysis in an attempt to evaluate the gestational fate of clomiphene-related conceptions (study series, n = 86). This latter series was contrasted with a series of pregnancies following bilateral ovarian wedge resection (BOWR) (n = 51) in a comparative analysis of gestational outcome event rates. Post-therapy follow-up was available for varying time spans of up to 15 years. A 12.8% twinning rate constituted the single most important complication of clomiphene therapy, resulting in measurable increments in perinatal morbidity and mortality rates. The observation of a 26.5% spontaneous abortion rate would seem to suggest that clomiphene-related conceptions are at little or more risk for spontaneous abortion than would have been expected from the infertile population under discussion. A 3.1% incidence of post-clomiphene birth defects was not increased as compared with commonly quoted rates for the population at large. The corresponding incidence rates of twinning, spontaneous abortion, and birth defects for the BOWR series were 0%, 21.6%, and 0%, respectively.
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Among 2,496 infertile Israeli women treated between 1964 and 1974, 143 cancer cases were observed as compared with 116.1 expected (standardized incidence ratio (SIR) = 1.2, 95% confidence interval (CI) 1.0-1.5) through 1991. Site-specific analysis revealed 12 ovarian cancers versus 7.2 expected (SIR = 1.6, 95% CI 0.8-2.9), 21 endometrial cancers versus 4.3 expected (SIR = 4.85, 95% CI 3.0-7.4), and 59 breast cancers versus 46.6 expected (SIR = 1.3, 95% CI 0.96-1.6). Sensitivity analysis revealed that confounding was unlikely to explain the raised risk of endometrial cancer, but nulliparity might explain the increased risk of ovarian cancer. The excess of endometrial cancer was prominent among patients with normal estrogen production but progesterone deficiency (SIR = 9.4, 95% CI 5.0-16.0). The risk for ovarian cancer was similar among the total groups of treated and untreated patients (SIR = 1.7 vs. 1.6). The standardized incidence ratio for endometrial cancer was higher among the treated group than the untreated group, although not significantly. Treatment with ovulation-inducing drugs does not appear to increase the risk for ovarian cancer, but its role cannot be completely excluded.
A recent Perspective article asserted that progesterone secretion during ovulatory cycles is the cause of breast cancer. However, we challenge most of the evidence developed in this publication. First, there is a lack of evidence that progesterone is mutagenic for breast cells. Cause of a cancer should mean initiation by mutation, as opposed to promotion. Second, subclinical ovulatory disturbances occur rather frequently in normal-length menstrual cycles. Third, the authors attribute a potential carcinogenic effect to progesterone secreted during menstrual cycles but not to progesterone during pregnancy. They did not discuss breast cancer evidence from progesterone/progestin therapeutics. They argue that in genetic primary amenorrhea, a hypothetic lower risk of breast cancer could be due to the lack of progesterone, despite the progesterone/progestin in hormone replacements these women receive. Fourth, they advocate a regulatory effect of progesterone on several genes potentially involved in cancer genesis. In particular, they attribute a lower risk of breast cancer in women with Mayer-Rokitansky-Küster-Hauser syndrome to a defect in the progesterone-stimulated Wnt4 gene. However, this defect is only present in a small subset. Thus, the postulated progesterone breast cancer risk is unconvincing, which we discuss point by point in this commentary.
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Data from previous studies suggest that infertility is a risk factor for endometrial cancer. We used data from the Cancer and Steroid Hormone Study to further characterize this relationship. The subject group comprised 399 women ages 20-54 with newly diagnosed epithelial endometrial cancer ascertained through six cancer registries. The control group comprised 3040 women in the same age range selected by random-digit telephone dialing from the same geographic areas where cancer patients resided. Compared with women who reported no fertility problem, women with physician-diagnosed infertility who had reported at least 2 years of infertility had an odds ratio for endometrial cancer, adjusted for age, of 1.7 (95% confidence interval 1.1-2.6). Women who reported infertility resulting from ovarian factors had an adjusted odds ratio of 4.2 (95% confidence interval 1.7-10.4). These results suggest that factors such as anovulation may explain much of the increased risk of endometrial cancer found among subgroups of infertile women.
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Breast cancer is the most common cancer in women worldwide. We investigated the association of hormonal contraceptive use and breast cancer in Thai women. A cohort study was conducted in Khon Kaen, Thailand. There were 70 cases of histologically confirmed breast cancer among 11 414 women aged 30 to 69 years who were recruited as participants in the cohort study during the period from 1990 through 2001. The study population was followed-up until December 31, 2011. To identify factors associated with incidence of breast cancer, hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using a Cox proportional hazards model. The 11 414 women provided a total observation time of 157 200 person-years. Breast cancer risk among women with a history of hormonal contraceptive use was 1.31 times that of women without such a history, but the difference was not statistically significant (95% CI, 0.65-2.65). No type of hormonal contraceptive was associated with a significant increase in breast cancer risk as compared with women who had never used hormonal contraceptives (oral contraception: HR = 1.35, 95% CI, 0.65-2.78; injection contraception: HR = 1.25, 95% CI, 0.56-2.80), and there was no relationship between duration of hormonal contraceptive use and breast cancer. There was no association between hormonal contraceptive use and breast cancer; however, this finding should be viewed with caution due to the small number of cases.
General Gynecology › Cancer and Fertility › Hormone Sensitive Cancer and Reproductive Care · Reproductive Endocrinology › Ovarian Hormones › Progesterone · Menstrual Cycle › Cycle Disorders › Ovulatory Disturbances
PMID 7304556 7304556 DOI 10.1093/oxfordjournals.aje.a113184 10.1093/oxfordjournals.aje.a113184 Cowan et al. 1981, Cowan 1981
Cite this article
Cowan, L. D., Gordis, L., Tonascia, J. A., & Jones, G. S. (1981). Breast cancer incidence in women with a history of progesterone deficiency. American journal of epidemiology, 114(2), 209-217. https://doi.org/10.1093/oxfordjournals.aje.a113184
Cowan LD, Gordis L, Tonascia JA, Jones GS. Breast cancer incidence in women with a history of progesterone deficiency. Am J Epidemiol. 1981;114(2):209-217. doi:10.1093/oxfordjournals.aje.a113184
Cowan, L. D., et al. "Breast cancer incidence in women with a history of progesterone deficiency." American journal of epidemiology, vol. 114, no. 2, 1981, pp. 209-217.
Keywords
Adult, Breast Neoplasms/epidemiology/etiology/mortality, Female, Humans, Infertility, Female/complications, Maryland, Maternal Age, Progesterone/deficiency, Prospective Studies, Risk, Progesterone, Biology, Breast Cancer, Cancer, Corpus Luteum Hormones, Data Collection, Diseases, Endocrine System, Hormones, Incidence, Infertility, Measurement, Menarche, Menopause, Neoplasms, Physiology, Population At Risk, Progestational Hormones, Progesterone--analysis, Prospective Studies, Reproduction, Research Methodology, Studies, Urogenital Effects, Urogenital System
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