Polycystic ovary syndrome and endometrial cancer

An association between polycystic ovary syndrome (PCOS) and endometrial carcinoma was first suggested in 1949. Since then, several studies have been published that appear to support this association, and it is common practice among gynecologists and physicians to prescribe hormonal treatment to reduce this perceived risk, although there is no consensus as to the subgroup of PCOS in whom this is required. The mechanism(s) underlying any association are also unclear, but it is again widely assumed that chronic anovulation, which results in continuous estrogen stimulation of the endometrium unopposed by progesterone, is a major factor. However, obesity, hyperinsulinemia, and hyperandrogenism, which are also features of PCOS, are risk factors for endometrial carcinoma, but it does not necessarily follow that the incidence or mortality from endometrial cancer is increased in women with the syndrome. Potential strategies to prevent endometrial cancer in PCOS women are discussed.     

Risk factors for atypical endometrial hyperplasia in infertile women:possible association with polycystic ovarv syndrome

Objective：Endometrial hyperplasia is considered as a precursor of endometrial carcinoma, in which oncogenic potential is low in hyperplasia without atypia, but high in atypical hyperplasia. The objective of this study was to identify the risk factors for atypical endometrial hyperplasia in infertile women. Methods：Fifty four infertile women with endometrial hyperplasia,which were selected from a large cohort of 2 098 women who desired for the future childbearing in our center, were diagnosed by hysteroscopy with directed biopsies or dilation and curettage （D＆C）, including 44 with hyperplasia without atypia, 10 with atypical hyperplasia. Clinical characteristics were recorded in terms of age, body mass index （BMI）, parity, insulin resistance, polycystic ovary syndrome （PCOS）. Statistical comparison was made between women with hyperplasia without atypia and atypical hyperplasia. Logistic regression analysis was employed to assess the contribution of PCOS, obesity and insulin resistance to atypical hyperplasia. Results：The incidence of endometrial hyperplasia in infertile women was 2.57 % （54/2098） , which included 10 women （0.48%） were diagnosed as atypical hyperplasia. PCOS in women with atypical hyperplasia （70% ,7/10） was significantly higher than those of hyperplasia without atypia （27.27% , 12/44 ）. Stepwise regression analysis showed that PCOS contributed maximally to atypical endometrial hyperplasia in infertile women. Conclusion：PCOS is an independent risk factor for atypical endometrial hyperplasia in women with infertility. The infertile women with PCOS are at an increased risk for atypical endometrial hyperplasia and endometrial cancer.     

Prevalence and clinical predictors of endometrial hyperplasiain anovulatory women presenting with amenorrhea.

The aim of the present study was to determine the prevalence and clinical predictors of endometrial hyperplasia (EH) in amenorrheic women with anovulation. Fifty-seven women were enrolled in the study. Of these, 43 were diagnosed to have polycystic ovary syndrome (PCOS) and 14 to have idiopathic anovulation. All women received transvaginal sonography to assess endometrial thickness (ET), patterns and abnormalities. At the same time, an endometrial biopsy was taken using a Pipelle instrument. The women's age, body mass index (BMI) and waist-to-hip ratio (WHR) were 32.0+/-6.0 years, 27.3+/-6.5 kg/m(2) and 0.82+/-0.06 (mean+/-standard deviation), respectively. Twenty (35.1%) and 19 (33.3%) women were classified as obese by BMI and WHR, respectively. Hypertension was found in 17 (29.8%) women. The prevalence of EH was 45.6%. Most cases were simple EH, and only one (1.75%) was simple EH with atypia. EH prevalence was 48.8% and 35.7% in PCOS and idiopathic anovulatory women, respectively. Age, BMI, WHR and ET did not predict EH, whereas the endometrial hyperechogenic pattern was a clinical predictor of EH with borderline significance. In conclusion, this study demonstrated that almost half of the anovulatory women with amenorrhea had EH and no significant predictor was found. In view of these findings, an endometrial biopsy should be performed in all women with this disorder.     

Endometrial thickness predicts endometrial hyperplasia in patients with polycystic ovary syndrome

Body mass index is predictive of sonographic endometrial stripe thickness, which in turn is predictive of endometrial hyperplasia in patients with polycystic ovary syndrome. For every 1-mm increase in endometrial stripe, the odds ratio of hyperplasia increased by 1.48 (95% confidence interval, 1.04-2.10).     

Diagnosis and management of endometrial hyperplasia

Endometrial hyperplasia (EH), with or without atypia, is a common gynecologic diagnosis and a known precursor of endometrial carcinoma, the most common gynecologic malignancy. During the reproductive years, the risk of EH is increased by conditions associated with intermittent or absent ovulation, in particular, polycystic ovary syndrome. After menopause when ovulation has ceased, EH is more common in women with conditions that increase levels of circulating estrogen such as obesity or estrogen replacement therapy. Women with EH are at increased risk for both concurrent and subsequent endometrial cancer. The risk of coexisting cancer in women with a diagnosis of EH at endometrial sampling is due to limitations in both endometrial sampling and the diagnostic reproducibility among pathologists. These diagnostic uncertainties add to the complexity of managing EH. This review offers a rational approach to prevention, diagnosis, and treatment of EH, including hormone therapy and conservative surgical methods.     

Risk Factors for Endometrial Cancer or Hyperplasia in Adolescents and Women 25 Years Old or Younger

Study ObjectiveTo evaluate characteristics of young women with endometrial hyperplasia or cancer.DesignRetrospective chart review.SettingTertiary care referral center.Participants, Interventions, and Main Outcome MeasuresWe included 10- to 25-year-old young women seen at a single institution between 2006 and 2017 with International Classification of Diseases 9th and 10th revision codes for endometrial cancer or hyperplasia (cases), or who underwent an endometrial biopsy with other benign pathologic diagnoses (controls). Exclusions included a diagnosis of Lynch syndrome. Comparisons were made using χ², Fisher exact, and nonparametric Wilcoxon rank tests.ResultsSixty-nine patients were identified: 13 cases, 54 controls, and 2 exclusions. Of the 13 cases, 3 had endometrial cancer, 5 had complex atypical hyperplasia (now called endometrioid intraepithelial neoplasia), and 5 had hyperplasia without atypia. A higher proportion of cases had a body mass index (BMI) greater than 30, compared with controls (76.9% vs 40.4%; P < .03). The proportion of patients who had a BMI greater than 30 and were smokers was significantly higher among cases (38.5% vs 9.3%; P < .02). The proportion of patients with a history of polycystic ovary syndrome (PCOS) and smoking was also significantly different between groups (30.8% vs 3.7%; P < .01).ConclusionIn women aged 25 years and younger with endometrial sampling, a BMI greater than 30 was statistically more common in patients with endometrioid intraepithelial neoplasia or cancer. Although smoking or PCOS alone was not related to endometrial hyperplasia or cancer in this small cohort study, there might be a relationship between endometrial abnormalities and multiple exposures, including smoking and BMI greater than 30 or smoking and a history of PCOS.     

Induction of ovulation in infertile women with hyperandrogenism and insulin resistance

The polycystic ovary syndrome is a common cause of anovulatory infertility. Women with severe insulin resistance are a unique subset of polycystic ovary syndrome. The syndrome of hyperandrogenism, insulin resistance, and acanthosis nigricans (HAIR-AN syndrome) is one presentation of the insulin-resistant subset of polycystic ovary syndrome. Insulin resistance and hyperandrogenism are caused by genetic and environmental factors. In women with anovulatory infertility caused by hyperandrogenism and insulin resistance, clomiphene citrate treatment often fails to result in pregnancy. For these women, weight loss and insulin sensitizers can be effective methods of inducing ovulation and pregnancy and may reduce the number of clomiphene-resistant women with polycystic ovary syndrome who are treated with gonadotropins, ovarian surgery, or in vitro fertilization-embryo transfer.     

Prevalence of endometrial cancer and hyperplasia in non-symptomatic overweight and obese women

BACKGROUND: Obesity is a public health problem and it is necessary to identify if non-symptomatic obese women must be submitted to endometrial evaluation. AIMS: To determine the prevalence of endometrial hyperplasia and cancer in non-symptomatic overweight or obese women. METHODS: A cross-sectional study was carried out in 193 women submitted to an endometrial biopsy using a Pipelle de Cornier. The findings were classified as normal, hyperplasia or cancer, and the results were compared to body mass index (BMI; kg/m(2)). For the purpose of statistical analysis, women were divided into two groups: women of reproductive age and postmenopausal women, and according to BMI as overweight or obese. RESULTS: The prevalence of endometrial cancer and hyperplasia was 1.0% and 5.8% in women of reproductive age and 3.0% and 12.1% in postmenopausal women, respectively. According to logistic regression, being in the postmenopause increased the risk of endometrial hyperplasia and cancer to 1.19 (95% confidence interval (CI): 0.36-3.90), while being postmenopausal and severely obese increased the odds ratio (OR) to 1.58 (95%CI: 0.30-8.23) and being postmenopausal and morbidly obese increased the OR to 2.72 (95%CI: 0.65-11.5). No increase in risk was found in women of reproductive age who were either overweight or obese. DISCUSSION: Our results show that non-symptomatic, severe or morbidly obese postmenopausal women have a high risk of developing endometrial hyperplasia or cancer; however, no such risk was found for women of reproductive age.     

Bariatric surgery and adolescent gynecology

PURPOSE OF REVIEW: This review summarizes the impact of bariatric surgery on gynecologic complications in the context of the extremely obese adolescent and reviews contraceptive considerations before and after adolescent bariatric surgery. RECENT FINDINGS: Eighteen percent of children and adolescents have a body mass index greater than the 95th percentile, with 4% of adolescents being greater than the 99th percentile. Gynecologic morbidities identified in obese adolescents include anovulatory complications such as acute menorrhagia, polycystic ovary syndrome and endometrial hyperplasia, and cancer. When conventional dietary and behavioral therapy fail to result in weight loss, specific criteria have been identified to justify bariatric surgery in extremely obese adolescents. Bariatric surgery in adult women often results in resumption of ovulatory menses, resolution of clinical and laboratory evidence of hyperandrogenism, and return of fertility. Adolescents are at risk for unintended pregnancies, and there are special concerns regarding pregnancy in bariatric patients. Specific contraceptive methods have particular potential risks, benefits, and drawbacks for use in obese adolescents. SUMMARY: Clinicians who provide care for extremely obese adolescents must be aware of the potential for gynecologic morbidities including polycystic ovary syndrome, dysfunctional bleeding and endometrial hyperplasia, expected gynecologic and fertility outcomes of weight loss surgery for teens, as well as the implications on contraceptive options.     

Women younger than 50 years with endometrial cancer

PURPOSE OF INVESTIGATION: The purpose of the study was to evaluate if known risk factors for endometrial cancer in menopausal women are also related to endometrial cancer in younger ages. METHODS: Eighty-one patients with a mean age of 46.3 years diagnosed with endometrial cancer (EC) (histologically confirmed) from January of 1992 to December of 2004 were included in the study. The EC group of patients was compared with 100 patients (control group) randomly selected from the gynecologic clinic (inclusion criteria: age 43-48 years) without any endometrial cancer diagnoses that were evaluated for the same factors. RESULTS: Mean BMI was 34.4 kg/m2 (SD = 8.8) in the first group and 28.3 (SD = 7.6) in the second one (p < 0.001). None of the women in the EC group reported any history of oral contraception. With the exception of hypertension and ovarian cancer (probably related to small numbers) all other comparisons were statistically significant (although some only marginally). DISCUSSION: From the results of our study, it seems that body mass index (BMI), parity, type of menstrual cycles, history of polycystic ovarian (PCO) syndrome and diabetes are possibly related to endometrial cancer in women younger than 50 years of age, and the strongest relation was found with increased BMI. Also, there was no increased incidence of hypertensive disease in the EC group. CONCLUSION: Prospective studies are needed for final conclusions.     

Endometrial abnormalities in infertile women

OBJECTIVE: To analyze retrospectively the frequency, long-term prognosis and pregnancy rate in infertile women diagnosed with endometrial hyperplasia or carcinoma by endometrial biopsy. STUDY DESIGN: From 1989 to 2000, endometrial biopsies were performed on 2,573 patients to investigate the cause of infertility. The main outcome measures were frequency, long-term prognosis and pregnancy rate for patients with each type of endometrial abnormality. RESULTS: Twenty-four patients (0.93%) were diagnosed with an endometrial abnormality. Of them, 10 were diagnosed with simple hyperplasia, 7 with complex hyperplasia, 3 with complex hyperplasia with atypia and 4 with endometrial carcinoma. All 4 patients (0.16%) with endometrial carcinoma were infertile as a result of complications arising from polycystic ovary syndrome. Two of them underwent hysterectomies. High-dose medroxyprogesterone acetate therapy combined with assisted reproductive technology resulted in pregnancy in 1 of the 2 patients with endometrial carcinoma. CONCLUSION: Of infertile women, 0.93% have endometrial abnormalities, and those with polycystic ovary syndrome have a high risk of endometrial carcinoma. Assisted reproductive technology combined with high-dose medroxyprogesterone acetate may be effective means of overcoming infertility, allowing women with endometrial carcinoma to readily achieve pregnancy.     

Definitions, prevalence and symptoms of polycystic ovaries and polycystic ovary syndrome

Polycystic ovarian morphology is seen on ultrasound in approximately 22% of women. Polycystic ovary syndrome (PCOS) is a common and perplexing endocrine disorder of women in their reproductive years, with a prevalence of up to 10%. Clinical expression of the syndrome varies but commonly includes menstrual cycle disturbance, hyperandrogenism, insulin resistance and obesity. Recently, the European Society for Human Reproduction and Embryology and the American Society for Reproductive Medicine (ESHRE/ASRM) achieved a new consensus regarding the definition of PCOS. This is now defined as the presence of any two of the following three criteria: (i) polycystic ovaries; (ii) oligo-/anovulation; and/or (iii) clinical or biochemical evidence of hyperandrogenism. This revised definition provides an international framework for the clinical assessment of PCOS and for future research and collaboration.     

Diagnosis of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is the most common endocrine disorders among women in reproductive age, but diagnostic criteria used in clinical practice are still controversial. In 1990 the National Institute of HEALTH (NIH) conference on PCOS recommended that diagnostic criteria should include biochemical evidence of hyperandrogenism and ovarian dysfunction (in the absence of non-classical adrenal hyperplasia) without considering the morphological diagnosis of polycystic ovary by ultrasound as an essential part of the diagnosis. In the Rotterdam PCOS workshop of May 2003, however, PCOS is diagnosed when 2 of the following criteria are recognized: oligomenorrhea and/or anovulation, clinical or biochemical signs of hyperandrogenism, ultrasound findings of polycystic ovary. Further-more, it is underlined that the metabolic study is not necessary for PCOS diagnosis, while it is suggested for "at risk patients" (obesity, diabetes, familiar and obstetrical history) with an oral glucose tolerance test (OGTT). A recent study carried out by our group underlined the role of ultrasound parameter, in particular suggesting a ratio between ovarian stroma area and total area of the ovarian section (S/A), with a cut-off of 0.34, as "gold parameter" for PCOS diagnosis, because it shows high sensitivity and specificity (96.3%, 97.0% for the S/A).     

Polycystic ovary syndrome: recent genetic contributions

Polycystic ovary syndrome is the most common endocrine disorder in women of reproductive age. It is characterized by hyperandrogenism, chronic anovulation and it is often associated with hyperinsulinemia, insulin resistance and dyslipidaemia. The pathophysiology of polycystic ovary syndrome seems to implicate primary defects in ovarian steroidogenesis, influenced by environment, insulin action and obesity. Polycystic ovary syndrome is probably both a multigenetic and environmental disease. Knowing the genes of polycystic ovary syndrome would be helpful to develop therapeutics and prevention. Genes of gonadotrophins, steroid hormone synthesis and insulin resistance seem not to be directly involved, except perhaps the CYP 11 a gene. On the other hand, identification of the signal transduction pathways involved in these genes may provide valuable information that can be applied to other clinical manifestations of polycystic ovary syndrome (follicular growth arrest, insulin resistance, obesity and endometrial cancer...).     

Clinical and metabolic features of polycystic ovary syndrome.

OBJECTIVE: To explore the clinical and metabolic features of Chinese women with polycystic ovary syndrome (PCOS). METHODS: The clinical data of 273 Chinese women diagnosed as having PCOS were retrospectively studied. RESULTS: Of these women 34.8% had hirsutism, 45.1% had acne, 94.1% had some menstrual abnormality, and 96.7% had typical appearances of polycystic ovaries on ultrasonographic examination. The prevalence of overweight women was 30.4%, and the prevalence of insulin resistance was 12.8% using the glucose to insulin ratio (GIR) and 21.6% using the homesostasis model assessment (HOMA). Body mass index was significantly correlated with fasting insulin level (r=0.50), GIR (r=0.37) and HOMA (r=0.53). CONCLUSION: Menstrual abnormality and polycystic ovaries were the main clinical manifestations in this cohort of Chinese women with PCOS. The prevalence of hyperandrogenism, obesity, and insulin resistance was lower in this cohort than in women from other races with the same condition. Ethnic differences needs to be considered when studying the clinical and metabolic features of women with PCOS.     

The investigation and management of severe hyperandrogenism pre- and postmenopause: non-tumor disease is strongly associated with metabolic syndrome and typically responds to insulin-sensitization with metformin.

BACKGROUND: An androgen-secreting tumor needs to be excluded in any woman with severe hyperandrogenism. We sought to characterize patients with biochemical hyperandrogenism in respect of tumor versus non-tumor etiologies, explore possible links between non-tumor hyperandrogenism and metabolic syndrome, and ascertain whether metformin therapy can elicit diagnostic reductions in serum testosterone (T). PATIENTS AND METHODS: Seven-year retrospective study of all women referred to a university hospital endocrinology service with baseline T >4.0 nmol/l. Dataset comprised age, menopausal status, body mass index (BMI), presence/absence of hypertension, diabetes, acanthosis or dyslipidemia, along with changes in BMI and serum T following intervention with metformin, oophorectomy or dexamethasone. Non-tumor hyperandrogenism was defined by normalization of serum T or >40% reduction from baseline. RESULTS: Four out of 18 cases had adrenal carcinoma that was clinically obvious at initial presentation (one virilized, three Cushingoid). The remaining 14 were characterized by metabolic syndrome (BMI: 39.9 +/- 8.1 kg/m(2)), serum T of 6.14 +/- 1.6 nmol/l, and nadir serum T following intervention of 2.2 +/- 1.04 nmol/l. Diagnostic reductions in serum T occurred in 11/12 patients treated with metformin. CONCLUSIONS: Non-tumor hyperandrogenism with markedly elevated serum T and associated metabolic syndrome is a defined clinical entity in postmenopause as well as in premenopausal women with polycystic ovary syndrome. This has hitherto been only sparsely documented in the published literature. A fall in serum T level in response to insulin-sensitizing therapy with metformin and lifestyle change may be a reassuring indicator that such women are highly unlikely to harbor an androgen-secreting tumor.     

Resectoscopic surgery may be an alternative to hysterectomy in high-risk women with atypical endometrial hyperplasia

STUDY OBJECTIVE: Endometrial hyperplasia is found in 2% to 10% of women with abnormal uterine bleeding (AUB). Up to 43% of patients with cytologic atypia harbor coexisting adenocarcinoma, and approximately 20% to 52% of atypical hyperplasias, if untreated, progress to cancer. The objective of this study was to estimate the incidence of atypical endometrial hyperplasia encountered during routine resectoscopic surgery in women with AUB and to evaluate the role of resectoscopic surgery in the management of women with AUB and atypical endometrial hyperplasia who refused and/or were at high risk for hysterectomy. DESIGN: Prospective cohort study (Canadian Task Force classification II-3). SETTING: University-affiliated teaching hospital. PATIENTS: From January 1990 through December 2005, the senior author (GAV) performed primary resectoscopic surgery in 3401 women with AUB. Among these, there were 22 women with atypical (17 complex, 5 simple) endometrial hyperplasia. INTERVENTIONS: All women underwent hysteroscopic evaluation and partial (n = 3) or complete (n = 19) endometrial electrocoagulation and/or resection. Subsequently, 6 women had hysterectomy and bilateral salpingo-oophorectomy (BSO). MEASUREMENTS AND MAIN RESULTS: The median (range) for age, parity, and body mass index were 55 years (24-78 years), 2 (0-4), and 30.1 kg/m2 (22.5-52.2 kg/m2), respectively. Among the 3401 women, there were 22 cases of atypical endometrial hyperplasia, 12 of which were incidentally diagnosed at the time of hysteroscopy (complex 10, simple 2, incidence 0.35%). After hysteroscopic diagnosis or confirmation of diagnosis, 6 women underwent hysterectomy and BSO. Of the remaining 16 women, followed for a median of 5 years (range 1.5-12 years), 1 was lost to follow-up, 1 had only a biopsy to preserve fertility, 1 died from lung cancer after 4 years, and 1 died from colon cancer after 5 years. One patient developed endometrial cancer after 10.5 years with postmenopausal bleeding. She remains alive and well 3.5 years after hysterectomy and BSO. The remaining 11 patients are amenorrheic at a median follow-up of 6 years (range 1.5-12 years). CONCLUSIONS: Resectoscopic surgery in 3391 women with AUB detected 12 incidental cases of atypical endometrial hyperplasia (incidence 0.35%). Skillful resectoscopic surgery may be an alternative to hysterectomy in women with AUB and atypical endometrial hyperplasia, who refuse or are at high-risk for hysterectomy and who are compliant with regular and long-term follow-up.     

Ultrasound and menstrual history in predicting endometrial hyperplasia in polycystic ovary syndrome

OBJECTIVE: To assess the role of endometrial thickness on vaginal ultrasound assessment and menstrual history in predicting endometrial hyperplasia in women with polycystic ovary syndrome (PCOS) who presented with infertility due to anovulation. METHODS: This was a prospective study in a university referral-based fertility and endocrine clinic. Fifty-six women with PCOS presenting with infertility due to anovulation underwent both vaginal ultrasound assessments and endometrial biopsies. The main outcome measures were the predictive value of sonographic endometrial thickness (primary objective) and the menstrual history with other clinical characteristics (secondary objective) for proliferative endometrium and endometrial hyperplasia in logistic regression analysis. Their predictive value was further examined by receiver operating characteristic curve analysis. RESULTS: Thirty-six PCOS patients (64.3%) had proliferative endometrium and 20 (35.7%) had endometrial hyperplasia. Five of the latter (25%) had cytologic atypia. Endometrial thickness less than 7 mm or intermenstrual interval less than 3 months (corresponding to more than four menstrual periods yearly) was associated with proliferative endometrium only. The endometrial thickness correlated positively with endometrial hyperplasia (P =.018) and, together with the average intermenstrual interval, were significant predictors of endometrial hyperplasia (P <.001). CONCLUSION: These findings point to the usefulness of obtaining a detailed menstrual history in women with PCOS by identifying those at increased risk of endometrial hyperplasia and who require an endometrial biopsy. The endometrial thickness corroborates this clinical impression and is particularly useful when the menstrual history is uncertain. Endometrial hyperplasia in this population is effectively excluded when the endometrial thickness is less than 7 mm.     

Estrogen and endometrial carcinoma.

1. It has become evident that the estrogen secreting tumors of the ovary are associated with endometrial carcinoma, but this association is most easily observed in the postmenopausal patient where the incidence of carcinoma has been reported at 10.3% (1. 02) to 24% (83). 2. The most consistent association of endometrial carcinoma is with polycystic ovarian disease, where 19 (34), 21 (152), and 25% (150) of young women with endometrial carcinoma had Stein-Leventhal syndrome (67). 3. A very significant discovery became known in 1967 when the peripheral aromatization of delta4 androstenedione to estrone was reported by Kase (94) and MacDonald (111,112). Since that time we have learned that endometrial carcinoma patients have an increased peripheral conversion (139) (0.1% compared to 0.027%), which is similar to that found in obese and aging patients, by Hemsell, et al (77). This can be 2 to 4 times greater than the young adult or the patient without cancer. Estrone produced peripherally in normal postmenopausal women can amount to 40-60 microng/day and rise as high as 120-180 microng/day in the endometrial neoplasia group (39). Similarly patients with polycystic ovary disease, hyperthecosis and lipoid cell tumors of the ovary demonstrate androgen excess with extraglandular conversion to estrone (2). 4. It has become apparent that the principal estrogen in the postmenopausal patient is estrone and that the estrone-estradiol ratio in the serum is higher in postmenopausal women with corpus cancer than similar patients without cancer (135). Clearly, we must find the effect of this estrone excess at the nuclear "acceptor" level; and does this imbalance create a hormonal environment conducive to the development of endometrial carcinoma when age (an extremely important factor) and an oncogenic agent are added? 5. With the lack of ovarian estrogen there is a relative excess of adrenal testosterone, dihydrotestosterone and delta4 androstenedione, the available precursors of extraglandular estrone (1). 6. With the passage of time it appears that endometrial carcinoma is associated with hypothalamic "hyperactivity" (31) which exhibits immunologic-biologic dissociation of LH as previously observed in persistent trophoblastic disease when measuring hCG. The significance of this is still unknown. In a like fashion a significant number of the at risk polycystic ovary disease patients have an increased LH secretion. 7. Patient susceptibility is required as seen in animal experiments where prolonged administration of stilbestrol is used and still only rabbits and mice developed a malignant change. 8. Long term exogenous estrogen appears to have caused malignant changes in the endometrium, but it was universally given over a prolonged period (4 or more years). The recent retrospective studies demonstrate an association of oral estrogen therapy with endometrial cancer, but prospective studies investigating dose and duration of all estrogen preparations need to be undertaken. 9...     

Malignant Ovarian Sertoli-Leydig Cell Tumor Localized With Selective Ovarian Vein Sampling

Sertoli-Leydig cell tumors (SLCT) are rare, comprising less than 0.5% of ovarian neoplasms. They are most often diagnosed in premenopausal women and may produce androgens, resulting in hirsuitism, voice deepening, frontal balding, terminal hair growth, and clitoromegaly. SLCT are malignant in 15%–20% of cases. We discuss a 25-year-old patient with persistent hyperandrogenemia. Noninvasive imaging cannot conclusively differentiate between SCLT and other diagnoses such as polycystic ovary syndrome, ovarian hyperthecosis, idiopathic hyperandrogenism, idiopathic hirsuitism, and 21-hydroxylase-deficient nonclassic adrenal hyperplasia. Selective ovarian vein sampling revealed a 15-fold greater testosterone production from the right ovary compared with the left, which guided appropriate surgical management.