Peripheral and ovarian venous concentrations of steroid and gonadotropin hormones in postmenopausal women with epithelial ovarian tumors

Peripheral serum concentrations of estrone (E1), estradiol (E2), testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS), cortisol, prolactin, LH, and FSH were measured in 28 postmenopausal women with epithelial ovarian tumors (12 ovarian cancer, 5 borderline malignant, 11 benign neoplasms) and in 15 controls before bilateral salpingo-oophorectomy and 1 and 8 weeks postoperatively. The levels of these hormones were also measured in ovarian venous blood of 15 patients with ovarian tumors. E2 was significantly higher in the tumor group than in controls preoperatively and the levels of E1 and E2 decreased after radical operation. Hormone levels were similar in the benign and malignant tumor groups. Only DHEAS levels in peripheral serum were significantly lower in ovarian cancer patients than in the group with benign neoplasm. This was not the case in testosterone and androstenedione measurements. The measured levels of the hormones in ovarian venous blood were highest in mucinous ovarian tumors. E2 and testosterone levels were higher in mucinous ovarian tumors than in others. LH(hCG)-receptor levels were measured in 24 specimens and none of these showed detectable concentrations of LH(hCG) receptor. The results indicate that of all epithelial tumors mucinous ovarian tumors had hormonal activity most often, and malignancy had no effect on hormonal activity.     

Secretion of androgens and estrogens by normal and neoplastic ovaries in postmenopausal women

Peripheral and ovarian venous concentrations of testosterone, androstenedione, estradiol-17 beta, and estrone were measured in 30 postmenopausal women. Ovarian venous concentrations of testosterone and estradiol-17 beta were 5.6 and 4.3 times the peripheral concentrations of women with normal ovaries. This suggests that the ovaries of postmenopausal women continue to secrete these two steroids. Mean peripheral testosterone concentrations in 14 postmenopausal women with a nonfunctional or functional ovarian tumor were increased significantly. Ovarian venous concentrations of these four steroids from the side draining the tumor-bearing ovary were increased in 40 to 80% of the women. The venous concentrations from the normal ovary were also increased in 22% or more of the women with an ovarian tumor. Any ovarian neoplasm in postmenopausal women may be associated with increased ovarian sex-steroid secretion.     

Effect of menopause and sex hormones on plasma lipids

Plasma cholesterol (TC), triglyceride (TG), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C) and estradiol, FSH, LH, testosterone, prolactin were determined in 102 cases of perimenopausal women. HDL-C HDL-C/TC, HDL-C/LDL-C decreased and LDL-C increased significantly after menopause, while TG increased in group of menopausal years beyond 11 (P less than 0.01). Postmenopausal women also showed abrupt decrease of estradiol and increase of FSH, LH, and slight decrease of prolactin (P less than 0.01), but no change in testosterone. Plasma lipids showed no correlation with sex hormones except estradiol, which was positively related with HDL-C and negatively with TC, LDL-C (P less than 0.001) but no relationship with TG (P greater than 0.05). The effects of surgical menopause was greater than that of natural menopause. This study suggested that the postmenopausal changes of plasma lipids are related to the decrease of estradiol and the ovaries should be preserved when perimenopausal women received pelvic operation whenever possible.     

Effect of exogenous estrogen on serum pregnenolone, cortisol, and androgens in postmenopausal women.

Previous studies from this laboratory have included reports on the serum concentrations of the following steroids in premenopausal and postmenopausal women: pregnenolone, 17-hydroxypregnenolone, progesterone, 17-hydroxyprogesterone, cortisol, corticosterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, testosterone, dihydrotestosterone, estone, and estradiol 17-beta. In general the steroid levels were lower in postmenopausal subjects, and this difference was significant at P smaller than 0.05 for 8 of the steroids. The significantly decreased peripheral level of steroids in the postmenopausal state can be explained by decreases either in ovarian secretion of steroids or in ovarian stimulation of the adrenal cortex. Since the contribution of the adrenal cortex to the peripheral levels of dehydroepiandrosterone sulfate (DHEA-S) is greater than 95% in premenopausal women, a plausible explanation for the marked drop observed in peripheral DHEA-S levels after menopause is that the ovary influences the steroidogenic activity of the adrenal cortex. In such cases a decrease in the stimulation of the adrenal cortex by some ovarian steroids would be expected. Estrogen therapy in 10 postmenopausal women resulted in significant increases in the serum levels of 3 of the steroids compared to those in untreated subjects, confirming the postulate that ovarian estrogens stimulate the secretion of adrenal androgens.     

Steroid production and responsiveness to gonadotropin in isolated stromal tissue of human postmenopausal ovaries

Specimens from the ovarian cortical stroma of 15 postmenopausal women were examined histologically and were incubated for 4 hours in Krebs' bicarbonate buffer containing 5.5 mM glucose and 1% bovine serum albumin. Specimens of normal postmenopausal stroma produced measurable amounts of androstenedione, estradiol, and progesterone in vitro. Specimens with stromal hyperplasia produced larger amounts of androstenedione and estradiol than those with normal stroma. Androstenedione was the predominant steroid produced in both groups. The nonnegligible formation of estradiol indicated an aromatizing capacity of the stromal tissue. The addition of hCG elicited a significant increase in cyclic AMP formation in specimens from ovaries with stromal hyperplasia, indicating a preserved responsiveness to gonadotropin in this type of ovaries.     

Virilization due to ovarian hyperthecosis in a postmenopausal woman

A 51-year-old woman presented with hirsutism and virilization of gradual onset. The serum gonadotropin concentrations were in the postmenopausal range, the serum testosterone concentration was markedly elevated (9.8 nmol/l) and the serum estradiol concentration (220 pmol/l) was elevated above the postmenopausal range. A selective venous catheterization study demonstrated raised serum testosterone and androstenedione levels in ovarian veins and suggested the presence of a left ovarian tumor. The raised peripheral estradiol level was shown to be due to ovarian hypersecretion. After bilateral oophorectomy the serum testosterone became normal. Ovarian histology revealed bilateral stromal hyperthecosis. Ovarian hyperthecosis is a rare but important cause of serum testosterone levels in the neoplastic range. This is the third case reported of postmenopausal virilization due to ovarian hyperthecosis and the first report of a selective venous catheterization study in such a patient.     

Endocrine changes after laparoscopic ovarian cautery in polycystic ovarian syndrome

Recently, laparoscopic ovarian cautery has been described as a method of ovulation induction in women with polycystic ovarian disease. In an attempt to determine the mechanism of action, serum levels of androstenedione, testosterone, luteinizing hormone, follicle-stimulating hormone, and estradiol were determined before and after the laparoscopic ovarian cautery in six women with polycystic ovarian disease who had failed to ovulate with clomiphene citrate and human chorionic gonadotropin. Six regularly cycling women undergoing laparoscopy for investigation of infertility or tubal ligation served as controls. In patients with polycystic ovarian disease but not in controls, serum androstenedione, testosterone, estradiol, and luteinizing hormone significantly decreased to nadir levels on postoperative days 3 and 4. In contrast follicle-stimulating hormone levels rose after operation. These results resemble those reported after ovarian wedge resection. Of the six treated women, five ovulated postoperatively and four conceived. Laparoscopic ovarian cautery appears to be a promising alternative treatment for patients with polycystic ovarian disease in whom initial medical management fails.     

High levels of serum allopregnanolone in women with premature ovarian failure

The endocrine characteristics of patients with premature ovarian failure (POF) have not been fully elucidated. The aim of the present study was to evaluate whether steroidogenic activity in women with POF is different with respect to fertile and postmenopausal subjects.

In particular, circulating levels of allopregnanolone, a neuroactive steroid involved in modulation of reproductive function in rats, have been evaluated and correlated with serum levels of Δ4 precursor (dehydroepiandrosterone sulfate (DHEAS)), A5 intermediates (androstenedione, 17-hydroxyprogesterone (17-OHP), progesterone) and final products (estradiol and testosterone) of androgens. Levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and sex hormone binding globulin (SHBG) were also determined. In all cases specific radioimmunological assays were used. Women with POF showed statistically significantly lower concentrations of 17-OHP, androstenedione and testosterone when compared to fertile controls, while no differences were found between women with POF and postmenopausal women. Serum DHEAS levels were similar in POF patients and in fertile controls and higher with respect to postmenopausal women. Serum allopregnanolone levels were significantly higher in women with POF than in postmenopausal and infertile women. A significant inverse correlation between allopregnanolone levels and menopausal age in patients with POF was observed while no significant correlation was found between allopregnanolone and progesterone, androstenedione, 17-OHP and testosterone levels. In conclusion, allopregnanolone is scarcely influenced by the reduction of ovarian and adrenal activity observed in POF.     

Serum estrogens and androgens in women with endometrial carcinoma

Fifty-two postmenopausal women with newly diagnosed endometrial carcinoma and 58 postmenopausal age-matched controls were studied concerning serum levels of estrone, total estrone, estradiol, androstenedione, testosterone, dehydroepiandrosterone and its sulphate, sex steroid hormone binding globulin, follicle stimulating hormone, and luteinizing hormone. The patients had a higher mean serum level of estradiol (P = 0.006) and a lower level of follicle stimulating hormone (P = 0.001) than the controls and the significant differences remained after the number of years since the menopause and body index had been taken into account. As the serum levels of steroid hormone binding globulin tended to be lower among patients than among controls (P = 0.084), the difference in the biological effect of estradiol between the two groups was probably greater than the difference in serum concentrations would indicate. No significant difference in the ratio of estrone to androstenedione or in the mean serum level of androstenedione was found between patients and controls. These data support the role of estrogen in the etiology of endometrial carcinoma.     

Cognitive function in association with sex hormones in postmenopausal women

Several studies have suggested gender differences in cognitive function, but data on the association between sex hormones and cognitive function are contradictory. The aim of our randomized double-blind study was to explore the possible relations between cognitive function and serum levels of sex hormones, oxytocin and insulin-like growth factor-I (IGF-I) in postmenopausal women. Two-hundred healthy postmenopausal women were randomly assigned to receive estrogen, testosterone or placebo treatment for 1 month. The associations of spatial ability, verbal fluency and verbal memory with serum levels of estradiol, testosterone, estradiol/testosterone ratio, androstanediol, oxytocin and IGF-I were analyzed. Spatial ability showed a negative correlation with serum estradiol, estradiol/testosterone ratio, oxytocin levels and a positive association with androstanediol levels. Verbal fluency displayed a negative relationship with serum levels of testosterone, IGF-I and a positive with estradiol/testosterone ratio. Verbal memory displayed a positive correlation to androstanediol. Data suggest that not only absolute levels of sex hormones but also the balance between estrogen and testosterone and their metabolites may be important for cognitive function in women.     

The impact of serum FSH and estradiol on postmenopausal osteoporosis related to time since menopause

Aim: To determine the impact on osteopenia/osteoporosis of serum follicle-stimulating hormone (FSH), estradiol levels and time since menopause in a group of Turkish postmenopausal women. Methods: Four hundred and thirty-three healthy postmenopausal women seen at the Marmara University Menopause Outpatient Clinic were enrolled for this prospective cohort study. The women were allocated to one of three groups according to the bone mineral density (BMD) of the lumbar vertebrae and total hip, as measured by dual energy X-ray absorptiometry (DEXA). Serum FSH, estradiol levels, age and time since menopause were compared between the groups. Results: The mean serum FSH, LH, estradiol and testosterone levels for women with normal, osteopenic and osteoporotic BMD at lumbar vertrebra L1-L4 and total hip were comparable. Time since menopause had a stronger predictive value for low BMD (osteopenia or osteoporosis) in the lumbar and hip areas than did serum FSH or estradiol levels. Conclusions: Our study showed that neither FSH nor E2 has a strong impact on postmenopausal BMD. However it appears that time since menopause has a weak non-significant association with postmenopausal osteopenia and osteoporosis.     

Follicular fluid steroid levels and ovarian steroid secretion in polycystic ovarian disease

Comparison of the plasma levels of steroids between ovarian and peripheral venous blood in polycystic ovarian disease revealed that polycystic ovaries secreted androstenedione, testosterone, dihydrotestosterone, dehydroepiandrosterone and 17-hydroxyprogesterone significantly more than healthy-ovaries at the early follicular phase of the cycle, whereas the levels of estradiol and progesterone did not differ from the control values. Follicular cyst fluid from polycystic ovaries showed significantly higher concentrations of testosterone, androstenedione and dehydroepiandrosterone and much lower levels of estrone, estradiol. progesterone and 17-hydroxyprogesterone than follicular fluid from healthy preovulatory follicles. Testosterone and estradiol did not. however, show any significant difference when follicles in polycystic ovaries were compared to those in healthy ovaries at early follicular phase of the cycle. According to these findings follicle development in polycystic ovaries is arrested at a stage corresponding to the early follicular phase of the cycle. Increased androgen and 17-hydroxyprogesterone secretion by polycystic ovaries seems to originate mainly from the hyperplastic theca interna cells.     

Ovarian enlargement as a possible marker of androgen activity in polycystic ovary syndrome.

This study has been carried out in an attempt to analyze clinical, hormonal and ultrasonography data and to evaluate their possible interrelationships in a group of 72 women with polycystic ovary syndrome (PCOS). Seventeen (23.6%) PCO women were found to have ovarian volume within normal range, while 72.2% had enlarged ovaries. Serum testosterone, androstenedione and DHEAS levels were higher in PCO women with enlarged ovaries when compared to patients who had ovarian volume within normal range, although the difference was not significant. However, when PCO patients were divided into subgroups according to the degree of ovarian enlargement, it was found that patients with the most enlarged ovaries had significantly higher serum androstenedione levels than those with normal ovarian volume (p = 0.039). Significant positive correlation was established between serum androstenedione concentration and ovarian volume (r = + 0.23, p less than 0.05). Hirsutism was found to be equally present in patients with normal ovarian volume (70.6%) and in patients with enlarged ovaries (71.2%) while oligomenorrhea was present more frequently among PCO women who had ovarian volume within normal range (64.7% vs. 40.4%). The results of our study allow us to suggest ovarian enlargement as a marker of excessive androgen production and disturbances of menstrual cycle in polycystic ovary syndrome.     

Response of a mucinous ovarian tumor of borderline malignancy to human chorionic gonadotropin

Plasma and urinary steroid hormones were measured before and after an injection of human chorionic gonadotropin (hCG) to a postmenopausal woman with a mucinous ovarian tumor of borderline malignancy. Hormones were also measured in blood from a vein draining the tumor, and circulating gonadotropins and plasma and urinary steroids were measured before and after tumor removal. Baseline levels of plasma progesterone (P), androstenedione (delta 4 A), and estradiol (E2), and urinary estrogens and pregnanediol were high; they increased dramatically in response to hCG and fell after tumor removal. A less striking increase in testosterone, dihydrotestosterone, dehydroepiandrosterone (DHEA), and DHEA sulfate was noted after hCG injection. A gradient existed between tumor vein and peripheral vein levels of P, 17 alpha-hydroxyprogesterone, delta 4 A, E2, DHEA, and cortisol. Plasma follicle-stimulating and luteinizing hormones initially low but rose to the postmenopausal range after surgery. These results indicate the presence of delta 4 and delta 5 androstene pathways within the tumor. The responsiveness of the tumor to hCG provides further evidence that hCG may be the endogenous stimulus to steroid hormone production by epithelial ovarian tumors.     

Reproductive hormone levels in gynecologic oncology patients undergoing surgical castration after spontaneous menopause.

The endocrine function of the ovary after menopause is perhaps less well understood than at any other time in the female life cycle. To evaluate the hormonal function of the ovary further at this stage of life, reproductive hormone levels were measured in 11 postmenopausal women admitted to the gynecologic oncology service for pelvic surgery which would involve bilateral oophorectomy. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, along with estradiol, testosterone, dehydroepiandrosterone sulfate (DHEA-S), and androstenedione levels, were measured preoperatively, on Postoperative Days 1 and 4, and at 6 weeks following surgery. Testosterone and androstenedione levels fell by half in these patients, whereas estradiol levels were unaffected. LH and FSH showed a fall in the immediate postoperative period, with a subsequent return to baseline levels by 6 weeks after surgery. DHEA-S levels were unaffected by surgery. There are no discernible differences in subjective menopausal symptoms postoperatively in postmenopausal women undergoing bilateral oophorectomy compared to their preoperative state. The data show that the long-held but inadequately proven thesis that postmenopausal oophorectomy dramatically reduces androgen levels is in fact true. This is further evidence that the postmenopausal ovary is an important source of potent and potentially aromatizable androgens.     

Pathological and endocrinological study of epithelial ovarian tumors in post-menopausal women

We have studied 37 cases of ovarian epithelial tumors in post-menopausal women, histopathologically and endocrinologically. The normal values for androstenedione, estrone, estradiol and progesterone in healthy post-menopausal women were less than 83 ng/dl, 75 pg/ml, 30 pg/ml and 0.6 ng/ml, respectively. The numbers of cases, the serum values for which were higher than normal, were 9 of 16 (androstenedione), 9 of 16 (estrone), 22 of 29 (estradiol) and 14 of 20 (progesterone). The serum levels of these 4 sex hormones in cases with ovarian stromal condensation (stromal cell hyperplasia) were higher than normal in 8 of 11 (androstenedione), 8 of 11 (estrone), 17 of 19 (estradiol) and 9 of 12 (progesterone), whereas those in cases with no stromal condensation were elevated in 1 of 5, 1 of 5, 5 of 8 and 5 of 7, respectively. After complete removal of the tumors, these elevated sex hormone levels dropped to normal. After the dexamethasone suppression test, the suppression rates for cortisol, 17-OHCS and 17-KS were 4 times as great as those of DHEA-S (dehydroepiandrosterone-sulfate), estrone, estradiol and progesterone. 17 beta-estradiol was localized in hyperplastic ovarian stromal cells in all cases with stromal condensation. We concluded that many of the ovarian epithelial tumors produce these sex hormones and that hyperplastic stromal cells are the source an increased amount of serum estradiol.     

GnRH-agonist therapy in women with the polycystic ovarian syndrome: effects on ovarian volume and on gonadotropin and sex steroid levels

Eleven patients with infertility and polycystic ovarian syndrome were treated with the GnRH agonist buserelin, 100 micrograms administered intranasally 6 times daily. The ovarian volume and morphology were monitored by vaginal sonography, and serum levels of hormones were measured by immunoassay. The mean ovarian volume was reduced from 13.0 +/- 4.1 cm3 to 9.1 +/- 3.1 cm3 after 42 days of treatment, p less than 0.001. The number of discernible ovarian microcysts was reduced from 11.9 +/- 2.1 to 9.6 +/- 2.9, p less than 0.05. The gonadotropin levels were reduced in all patients; however, there was no direct relationship between the reduction in ovarian volume loss and the concomitant decrease in LH or FSH levels. The levels of testosterone and androstenedione were normalized, whilst estradiol was suppressed to postmenopausal levels during the treatment period. The decrease in ovarian volume and the suppressed levels of ovarian steroids therefore seem to be related to the inhibition of the pituitary-ovarian axis with the GnRH agonist.     

The androgenic profile of women with non-insulin-dependent diabetes mellitus

OBJECTIVE: To evaluate the androgenic profile of women with non-insulin-dependent diabetes mellitus. STUDY DESIGN: This case-control study evaluated the clinical, hormonal and ultrasonographic characteristics of women of reproductive age with non-insulin-dependent diabetes mellitus and compared them with those of age- and weight-matched controls. Radioimmunoassays were used for total testosterone, estradiol, dehydroepiandrosterone sulfate (DHEAS) and androstenedione. Sex hormone-binding globulin (SHBG), luteinizing hormone (LH) and follicle stimulating hormone (FSH) were analyzed by fluoroimmunoassays. Ovarian appearance and volume were assessed by transvaginal or transabdominal ultrasonography. RESULTS: The prevalence of polycystic ovary syndrome was higher in diabetic patients than in the general population as reported earlier. Hirsutism was also more prevalent in diabetic patients (p < 0.05). The serum levels of FSH, LH, estradiol, total testosterone, androstenedione and DHEAS were significantly higher in diabetic patients than in the control group (p < 0.05). In contrast, the levels of SHBG were lower in diabetic patients (p < 0.05). The rates of ultrasonographically apparent polycystic ovaries and greater ovarian volumes were also higher in diabetic patients (p < 0.05). CONCLUSION: Women with non-insulin-dependent diabetes mellitus seem to have biochemical and clinical hyperandrogenism when compared with nondiabetic controls.     

Hypergonadotropinemia with estradiol secretion in peri- and postmenopausal period

Plasma gonadotropins and estradiol levels were evaluated in 155 peri- and postmenopausal women. The average menopausal age was 52.5 years in 56 postmenopausal women. Plasma FSH and LH levels showed hypergonadotropinemia in many premenopausal women 45-49 years old, whose plasma estradiol levels, however, sometimes remained higher than 25 pg/ml. It was observed that 19 of 38 women (50%) had an estradiol level exceeding 25 pg/ml, of those 50-59 years old, whose gonadotropin level showed hypergonadotropinemia in 29 cases (76.3%). Ovarian vein levels of estradiol obtained during laparotomy of 21 patients were significantly higher than peripheral vein concentrations. In 3 of 5 climacteric women with irregular menstrual intervals and whose plasma gonadotropin level was within the postmenopausal range, some degree of estradiol secretion in the ovarian vein was detected. Estradiol was still present in the ovarian vein blood of some postmenopausal women. These data show that the basal gonadotropin level may become high several years before the menopause and that some ovarian function may be preserved after the menopause. Furthermore, it is possible that estrogen secretion may be disturbed by consistent hypersecretion of gonadotropins in the climacteric period.     

Bilateral luteomas of pregnancy in a patient with diabetes

A patient with diabetes and luteomas of the ovaries demonstrated a significant and progressive rise in the serum levels of androstenedione and testosterone during pregnancy. The levels of these hormones were also elevated in cord blood and ovarian fluid. The increased insulin requirement to maintain euglycemia was observed at an earlier date in this pregnancy than in her previous pregnancy.