Hirsutism, polycystic ovarian disease, and ovarian 17-ketosteroid reductase deficiency

We studied an 18-year-old woman with progressive hirsutism, secondary amenorrhea, and polycystic ovarian disease. Excess androstenedione was secreted by the ovaries, most likely because of a genetic deficiency of ovarian 17-ketosteroid reductase, the enzyme that converts androstenedione to testosterone. Markedly elevated basal plasma levels of androstenedione, estrone, and testosterone were regulated by gonadotropin but not by ACTH. The rate of androstenedione production in the patient's blood at base line and after administration of dexamethasone was very high (10.0 to 11.6 mg per day; value in control women with hirsutism, less than 4.1 mg per day), whereas her blood production of testosterone was 0.64 to 0.7 mg per day, similar to or higher than that in control women with hirsutism. The fractional blood conversion ratio of androstenedione to testosterone was normal (5.6 percent). Thus, 88 to 93 percent of the testosterone in the blood was derived from the peripheral conversion of androstenedione, and very little testosterone was secreted by the ovaries. These in vivo biochemical data suggest that the patient had a deficiency of ovarian 17-ketosteroid reductase activity but normal pubertal activity. The patient's two younger sisters with peripubertal symptoms of androgen excess also had elevated serum levels of androstenedione. We propose that the increased secretion of androstenedione in the three siblings in this family was probably due to a genetic deficiency of ovarian 17-ketosteroid reductase.     

Gonadal function in men with the Martin-Bell (fragile-X) syndrome

We evaluated testicular function in 15 men with the Martin-Bell (fragile-X) mental retardation syndrome. Macro-orchidism was present in all subjects. Their mean serum LH and FSH levels and plasma testosterone and dihydrotestosterone levels were normal. The mean plasma levels of androstenedione, 17-hydroxyprogesterone, and progesterone were slightly elevated above the normal range, whereas the plasma levels of dehydroepiandrosterone and dehydroepiandrosterone-sulfate were normal. The response in the levels of plasma testosterone following a 5 day period of hCG stimulation was normal in 8 subjects and there was no abnormal accumulation of androgen precursors. The level of 5 alpha-reductase activity and androgen receptor binding was normal in genital skin fibroblasts derived from 3 of these patients. The response of gonadotropin secretion to GnRH stimulation was normal in the 8 men who were tested. Therefore, our data are consistent with the hypothesis that testicular enlargement in men with the Martin-Bell syndrome is not mediated by hormonal factors.     

Girls with virilisation in childhood: a diagnostic protocol for investigation.

AIM: To analyse critically a protocol for the investigation of girls presenting with virilisation in childhood. METHODS: Twenty five girls aged 1.6-8.7 years with features of virilisation were evaluated. Twenty four had presented with pubic hair, eight with auxilliary hair, seven with facial acne, four with clitoromegaly, and 10 with tall stature. They underwent clinical assessment (height, weight, height velocity, staging of puberty, physical examination for acne, body odour, and clitoromegaly) and laboratory assessment comprising basal concentrations of cortisol, 17 OH-progesterone (17 OHP), androstenedione, dehydroepiandrosteronesulphate (DHEAS), testosterone, and oestradiol. The above steroids were also measured during the short synacthen test (0.25 mg intramuscularly) in 16 subjects and low dose dexamethasone suppression tests (0.5 mg at six hourly intervals over 48 hours). Pelvic ultrasound, computed tomography and magnetic resonance imaging of adrenals were carried out when the biochemical findings suggested that there might be an autonomous source of androgen secretion. RESULTS: Clinical and laboratory assessments differentiated the patients into three diagnostic categories: adrenarche (18 cases), congenital adrenal hyperplasia (five cases), and adrenocortical tumour (two cases). The last had elevated concentrations of DHEAS, 1.5 and 19.1 mumol/l (normal value < 0.5 mumol/l), androstenedione, 24.6 and 21.8 nmol/l (normal < 1 nmol/l), and testosterone, 4.5 and 2.4 nmol/l (normal < 0.8 nmol/l), with none suppressing on dexamethasone suppression. Congenital adrenal hyperplasia subjects had elevated basal serum concentrations of 17 OHP (n = 4): 250, 140, 14, and 14.1 nmol/l (normal < 10 nmol/l) and elevated peak values of 17 OHP after synacthen (n = 3): 76, 179.5, and 175 nmol/l. Adrenarche patients had elevated basal concentrations of DHEAS (median: 2.3 mumol/l; n = 17) and androstenedione (median 2.6 nmol/l; n = 17). Nine patients also had elevated basal serum testosterone concentrations (median 0.9 nmol/l). Peak values of 17 OHP after synacthen were significantly different from baseline (n = 12) and were < 50% of the lowest value in congenital adrenal hyperplasia. Serum DHEAS, androstenedione, and testosterone suppressed following dexamethasone suppression (n = 16), thereby distinguishing adrenarche patients from adrenal tumour patients. Clinical details did not distinguish patients, except for clitoromegaly which was present only in the tumour and congenital adrenal hyperplasia patients. CONCLUSIONS: This protocol proved useful and practical in cases of virilisation presenting particular diagnostic difficulty.     

Inhibition of human adrenal androgen secretion by ketoconazole

Summary The effect of ketoconazole on adrenal androgen secretion was examined in 15 patients with elevated serum androgens. In a dose of 600 mg per day orally ketoconazole inhibited the biosynthesis of all measured androgens. The mean reduction in serum levels of dehydroepiandrosterone sulfate was 32%, of dehydroepiandrosterone 54%, of androstenedione 52%, and of testosterone 43%; mean serum levels of cortisol only fell by 19%. The reduction in serum androgen levels was first significant 24 h after beginning of treatment and persisted as long as the drug was administered. We conclude that ketoconazole inhibits adrenal androgen biosynthesis more pronouncedly than cortisol biosynthesis. This might be of clinical benefit in the treatment of hirsutism and other states of androgen hypersecretion.Abbreviations CV coefficient of variation - MV mean value - SEM standard error of the mean - f female - m male - K ketoconazole - ACTH adrenocorticotropic hormone - DHEA dehydroepiandrosterone - DHEAS dehydroepiandrosterone sulfate - A androstenedione - T testosterone - F cortisol - P progesterone - H hirsutism - C Cushing's disease - EAS ectopic ACTH syndrome - ATU adrenal tumor     

Maternal serum androgens in human pregnancy: early increases within the cycle of conception

Previous studies have demonstrated elevations in testosterone and androstenedione initiated within the cycle of conception in pregnant non-human primates, and minimal data in the human support the same picture. In the present study we have investigated a group of patients scheduled for artificial insemination with regular menstrual cycles. For this study all patients provided blood samples at 5 days after the luteinizing hormone (LH) surges and daily through the luteal phase and into early pregnancy (n = 12). Patients who did not become pregnant served as normal controls (n = 9). We have measured 17- hydroxyprogesterone (17-OHP) as a marker of luteal activity not obscured by progesterone within the cycle of conception and testosterone and androstenedione as the major androgens. There were no significant changes in testosterone and androstenedione in the non- pregnant controls, but both testosterone and androstenedione were significantly elevated in the pregnant luteal phase, with the first increases occurring at 15 and 14 days respectively after the LH surge. Three of 12 pregnant patients did not demonstrate a dramatic increase in either testosterone or androstenedione and when examined more carefully a corresponding lack of increase in 17-OHP in those same subjects indicated less than optimal luteal activity, suggesting that these androgens were products of the corpus luteum. In three subjects in which consecutive non-pregnant and pregnant cycles were followed there was a dramatic increase from the non-pregnant luteal phase to the pregnant luteal phase indicating that the more important observation may be the concentrations of androgens in the conceptive luteal phase compared to some baseline, either previous luteal phase or even follicular phase. We have also studied changes in dehydroepiandrosterone sulphate and found that there was no significant contribution to this increase in androgens in early conception. These studies demonstrate a significant increase in both testosterone and androstenedione presumably of ovarian, specifically luteal, origin and that adrenal androgen production is not a factor in these changes.      

An Unusual Hormone Pattern in a Virilized Woman Affected by Sertoli-Leydig Cell Tumor

A 24 year old woman was admitted to hospital because of hirsutism, virilism and amenorrhea, which had appeared 6 months earlier. Endocrinological evaluation showed a slightly elevated serum level of testosterone (1.2 ± 0.05 ng/ml), normal plasma levels of dehydroepiandroste-ronesulfate (DHEA-S) (2,070 ± 6 ng/ml), androstenedione (1.8 ± 0.5 ng ml) and sex hormone-binding globulin (SHBG)(42 ± 3nM/L); there was normal urinary 17 keto-steroid (17-KS) excretion (11.7 mg 24 h), low urinary estrogen (E) excretion (3 + 0.4//g 24 h), suppressed basal gonadotropin concentrations (LH 0.9//III ml; FSH 3.2,uUI/ml) and an exaggerated response to the LH RH test. At laparotomy, a monolateral ovarian tumor was found, which was proved histologically to be a Sertoli-Leydig cell tumor. After tumor ablation, a regular menstrual cycle followed and progressive reduction of virilism was noted. This was followed within 4 months by complete normalization of LH, FSH, estrogen and progesterone serum levels. The responsiveness to LH RH also became normalized. Two years after this operation, the patient had a normal pregnancy. This case of virilization in a woman affected by a benign Sertoli-Leydig cell tumor was primarily characterized by an unusual response of the hypothalamo pituitary axis against an endocrinological background of notable alteration of the androgen/estrogen ratio, where the androgens were slightly increased and the estrogens greatly reduced. Acta Pathol Jpn 39: 755-758, 1989.     

Influence of endogenous androgens on carotid wall in postmenopausal women

OBJECTIVE: There is increasing evidence of a direct association between normal androgen levels and reduced cardiovascular morbidity and mortality in women. After menopause the influence of estrogens declines, whereas that of androgens increases. Therefore, we investigated the effects of androgens on atherosclerosis in postmenopausal women, by using carotid artery intimal-medial thickness as a marker of vascular damage. DESIGN: Blood pressure, body mass index, waist-to-hip ratio, serum dehydroepiandrosterone sulfate, androstenedione, total and free testosterone, estrone, insulin, lipid profile, and glucose were evaluated in 44 women in stable physiological menopause. All subjects underwent carotid ultrasound (Biosound 2000 II s.a. high-resolution unit). RESULTS: Spearman correlation coefficients indicated that serum androstenedione and free testosterone were negatively associated with several carotid intimal-medial thickness measures with correlation coefficients (r) ranging from 0.477 to 0.397 (p < 0.01-0.04). Moreover, age-adjusted androstenedione and free testosterone highest tertiles showed intimal-medial thickness values significantly (p < 0.03-0.05) lower than the other tertiles. There was a favorable association between hormones and the most important cardiovascular risk factors. This association, however, did not reach statistical significance. Stepwise multiple regression analysis showed that the inverse relationships between the hormones (androstenedione and free testosterone) and several intimal-medial thickness measures were maintained (F: 4.15-6.07, p < 0.05-0.02) after adjustment for major cardiovascular risk factors. CONCLUSIONS: Our data demonstrate that in postmenopausal women endogenous steroid precursors and androgens are inversely related to carotid intimal-medial thickness, an established marker of atherosclerosis. In addition, these hormones show favorable associations with cardiovascular risk factors. Therefore, our study suggests that, after menopause, normal androgen levels may benefit the carotid artery wall.     

Ovarian and adrenal steroid production: regulatory role of LH/HCG

BACKGROUND: The contribution of the adrenal glands to the total circulating steroid pool in women is not well known. There is evidence that human adrenals express the LH receptor gene and that LH may affect adrenal androgen secretion. METHODS: HCG stimulation tests (a single dose of 5000 IU i.m.) were performed in women at reproductive age (group 1, n = 6, age 21--39 years) before and after treatment with a GnRH agonist for 3 weeks, and in oophorectomized post-menopausal women (group 2, n = 6, 47--59 years) during and after estrogen replacement therapy (ERT). RESULTS: HCG did not stimulate the secretion of cortisol, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS) in group 2. In contrast, in group 1, the basal concentrations of serum 17-hydroxyprogesterone (17-OHP), androstenedione, testosterone and estradiol (E(2)) were stimulated significantly (17-OHP 105%, androstenedione 31%, testosterone 20%, E(2) 136%) by HCG, and the treatment with GnRH agonist decreased the responses. The basal serum concentrations of these steroids were significantly lower in oophorectomized women (17-OHP 57%, androstenedione 46%, testosterone 25%), and HCG did not increase these levels. It can be approximated that the ovarian contribution to the circulating levels of 17-OHP, androstenedione and testosterone is 25--30%, and that the adrenals are the primary source of cortisol, DHEA and DHEAS. CONCLUSION: LH/HCG does not have a major role in the regulation of adrenal steroid synthesis in endocrinologically healthy women.     

Androgen excess in women – A health hazard?

A significant body of evidence suggests that androgens in women may play a role in the genesis of central adiposity and type 2 diabetes. There are two principal sources of circulating androgens in females: the ovary and the adrenal gland. In hyperandrogenic women, there are elevated serum concentrations of androstenedione and testosterone and, in up to 50% of the women, dehydroepiandrosterone sulfate (DHEAS). The androgen precursor DHEAS is of exclusive adrenal origin, suggesting that hyperandrogenic women have an elevated proportion of adrenal androgen production and secretion. Another cause of androgen excess in reproductive-age women is a decreased conversion of testosterone to estradiol by the aromatase enzyme complex. In this review, we will discuss the hypothesized clinical sequel of elevated androgens in women - an aspect of women's health highly neglected. Furthermore, an attempt is made to appreciate what causes the androgens to initially rise from normal levels, allowing the onset of pathophysiological processes towards diseases.     

Serum anti-Müllerian hormone levels remain high until late reproductive age and decrease during metformin therapy in women with polycystic ovary syndrome

BACKGROUND: Anti-Müllerian hormone (AMH) is secreted by granulosa cells of ovarian early developing follicles and its serum levels have been shown to correlate with small antral follicle number. Since the pronounced androgen secretion from follicles/stroma in women with polycystic ovary syndrome (PCOS) remains until late reproductive age, and since AMH reflects the number of antral follicles, it was of interest to study the possible age-related relationship between AMH, androgens and follicle number in women with PCOS and in control women. Moreover, the possible effect of metformin on serum AMH levels and the relationship to follicle count and volume were studied. METHODS: Forty-four healthy women (aged 21-44 years) and 65 women with previously diagnosed PCOS (aged 16-44 years) participated in the study. Serum basal AMH levels were correlated with those of serum androstenedione, testosterone, estradiol (E2), LH, FSH and inhibin B, and with follicle number. The effect of metformin on serum AMH concentrations, follicle number and ovarian volume was studied in 26 women (aged 20-41 years) with PCOS after 6 months of treatment. RESULTS: Serum AMH levels were 2- to 3- fold higher in PCOS women than in healthy women. In control women, serum AMH levels correlated positively with those of serum androstenedione (r = 0.564, P < 0.001) and testosterone (r = 0.328, P = 0.036) and negatively with serum FSH concentrations (r = -0.374, P = 0.012) and age (r = -0.691, P<0.001). In women with PCOS, serum AMH levels correlated positively with those of androstenedione (r = 0.311, P = 0.011) and testosterone (r = 0.310, P = 0.011) and with follicle count (r = 0.352, P = 0.012), and negatively with age (r = -0.300, P = 0.014). Serum AMH levels, the number of antral follicles and ovarian volume decreased significantly during metfromin treatment. CONCLUSIONS: Serum AMH levels decreased with age both in healthy women and in women with PCOS, although they were always 2- to 3-fold higher and remained elevated until 40 years of age in PCOS subjects. Thus, since serum AMH levels correlate well with antral follicle count and serum androgen levels, the measurement of AMH could be used as a tool to assess ovarian ageing, to diagnose polycystic ovaries/PCOS and to evaluate treatment efficacy.     

Lack of dehydroepiandrosterone in type I and II hereditary angioedema and role of danazol in steroid hormone conversion

BACKGROUND: Hereditary angioedema (HAE) is successfully treated with danazol, a therapeutic steroid compound. To investigate hormones of the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axis in patients with HAE with and without danazol. METHODS: We included 16 patients with type I HAE, nine patients with type II HAE, and 16 healthy subjects. Serum levels of adrenocorticotropic hormone (ACTH), cortisol, androstenedione, dehydroepiandrosterone (DHEA), free testosterone, and 17beta-oestradiol were measured. RESULTS: Serum levels of ACTH were markedly decreased in patients with type II HAE compared to the other groups (P < 0.001). Serum cortisol was similar between groups but danazol treatment decreased cortisol levels, particularly in women (P = 0.019). Serum levels of DHEA were significantly decreased in all patients with type I and II HAE compared to controls (P < 0.05), which was only partly dependent on prior danazol therapy as patients without danazol had also decreased serum levels of DHEA (P < 0.05). Furthermore, free testosterone serum levels were markedly increased in patients under danazol (P < 0.005) and the ratio of 17beta-oestradiol/free testosterone was significantly decreased in these patients (P < 0.005). CONCLUSIONS: This study demonstrated decreased DHEA in patients with type I and II HAE independent of danazol therapy, which was particularly evident in women. It also demonstrates that danazol induced a marked up-regulation of free testosterone in relation to precursors and downstream 17beta-oestradiol. In HAE, there seems to be a primary lack of the adrenal androgen DHEA.     

Endocrine profile in serum and follicular fluid differs after ovarian stimulation with HP-hMG or recombinant FSH in IVF patients

BACKGROUND: Highly purified menotrophin (HP-hMG) has been associated with fewer oocytes retrieved and a higher proportion of top-quality embryos compared with recombinant FSH (rFSH). METHODS: A randomized, assessor-blind, multinational trial in 731 women undergoing IVF after stimulation with HP-hMG (MENOPUR) (n = 363) or rFSH (GONAL-F) (n = 368) following a long GnRH agonist protocol was conducted. Blood was collected before, during and after stimulation. Fluid was collected from follicles > or =17 mm. RESULTS: Serum androstenedione, total testosterone and free androgen index (FAI) were higher (P < 0.001) with HP-hMG than with rFSH after starting stimulation. At the end of stimulation, serum estradiol was higher (P = 0.031) with HP-hMG, whereas progesterone was higher (P < 0.001) with rFSH, even after adjusting for ovarian response. Serum LH was not different between treatments. Mean mid- and end-follicular hCG levels in the HP-hMG group were 2.5 and 2.9 IU/l, respectively. Follicular fluid levels of FSH, LH, hCG, androstenedione, testosterone, FAI and estradiol and ratios of estradiol:androstenedione, estradiol:total testosterone and estradiol:progesterone were higher (P < 0.001) with HP-hMG, whereas progesterone was higher (P < 0.001) with rFSH. CONCLUSION: Major differences in serum and follicular fluid endocrine profile exist after stimulation with HP-hMG or rFSH. Exogenous LH activity induces a differential endocrine environment influencing oocyte quantity and quality, which may be of relevance for clinical outcome.     

In vitro bioassays for androgens and their diagnostic applications

Androgen levels are measured in today's clinical practice almost exclusively by immunoassays. The androgen that is most frequently determined is testosterone (T), but sometimes also the levels of other testicular, ovarian and adrenal androgens such as 5alpha-dihydrotestosterone, androstenedione, dehydroepiandrosterone and its sulphate may be determined. In many instances, especially when androgen levels are low (as in women and children), the quality of the immunomeasurements is insufficient and the correlation between hormone levels and clinical symptoms is poor. One alternative to improve the clinical relevance of androgen measurements is provided by the recently developed in vitro bioassays of total androgen bioactivity in serum. These assays are not yet ready for routine laboratory diagnostics, but they provide a useful tool for clinical research in disturbances of androgen production. Another application of these assays is the screening for androgenic and antiandrogenic activity in chemical compounds, environmental samples and when suspecting androgen abuse. The purpose of this article is to introduce the current problems of androgen measurement by immunoassays, to describe the novel in vitro bioassay techniques and to review the current information on their application in clinical research.     

An unusual hormone pattern in a virilized woman affected by Sertoli-Leydig cell tumor. Report of a case

A 24-year-old woman was admitted to hospital because of hirsutism, virilism and amenorrhea, which had appeared 6 months earlier. Endocrinological evaluation showed a slightly elevated serum level of testosterone (1.2 +/- 0.05 ng/ml), normal plasma levels of dehydroepiandrosteronesulfate (DHEA-S) (2,070 +/- 6 ng/ml), androstenedione (1.8 +/- 0.5 ng/ml) and sex hormone-binding globulin (SHBG)(42 +/- 3 nM/L); there was normal urinary 17-ketosteroid (17-KS) excretion (11.7 mg/24 h), low urinary estrogen (E) excretion (3 +/- 0.4 micrograms/24 h), suppressed basal gonadotropin concentrations (LH 0.9 microUI/ml; FSH 3.2 microUI/ml) and an exaggerated response to the LH-RH test. At laparotomy, a monolateral ovarian tumor was found, which was proved histologically to be a Sertoli-Leydig cell tumor. After tumor ablation, a regular menstrual cycle followed and progressive reduction of virilism was noted. This was followed within 4 months by complete normalization of LH, FSH, estrogen and progesterone serum levels. The responsiveness to LH-RH also became normalized. Two years after this operation, the patient had a normal pregnancy. This case of virilization in a woman affected by a benign Sertoli-Leydig cell tumor was primarily characterized by an unusual response of the hypothalamopituitary axis against an endocrinological background of notable alteration of the androgen/estrogen ratio, where the androgens were slightly increased and the estrogens greatly reduced.     

Ovarian steroidogenic response to human chorionic gonadotrophin in obese women with polycystic ovary syndrome: effect of metformin.

BACKGROUND: The aim of the present study was to investigate the steroidogenic response pattern to HCG in obese women with polycystic ovary syndrome (PCOS) and the possible effects of metformin treatment on it. METHODS: A single injection of human chorionic gonadotrophin (HCG, 5000 IU) was given to 12 obese [body mass index (BMI) > or = 27 kg/m2] women with PCOS and to 27 control women. Blood samples for assays of 17alpha-hydroxyprogesterone (17-OHP), androstenedione, testosterone and oestradiol were collected at baseline and 1, 2 and 4 days after the injection. Responses to HCG were also assessed in the PCOS women after 2-month treatment with metformin (500 mg x 3 daily). RESULTS: Serum 17-OHP and oestradiol concentrations peaked at 24 h in the PCOS women and preceded the maximum testosterone concentration, which was seen at 48 h. In the control women the maximum concentrations of all these steroids were reached 96 h after HCG. After metformin treatment, the basal serum testosterone concentration and the areas under the androstenedione (AUC(A)) and testosterone (AUC(T)) response curves after HCG decreased significantly. CONCLUSIONS: The results demonstrate that obese PCOS women have a male-type steroidogenic response pattern to a single injection of HCG and a higher androgen secretory capacity than control women, which may be explained by the increased thecal cell activity in the polycystic ovary. The slight alleviation of hyperandrogenism brought about by metformin therapy appears to be due to its effect on ovarian steroidogenesis possibly mediated by decreased insulin action.     

Sexual expression and its determinants in the post-menopausal woman

Anatomic, hormonal, psychosocial and psychosexual variables of sexual expression were evaluated in 69 non-patient post-menopausal women. Subjects received a 2-h individually administered interview, a gynecologic examination with subjective scoring of vaginal atrophy, and serum determinations of estrone. estradiol, and androstenedione, testosterone, FSH and LH. Sexual repertoire of the 34 coitally active (coitus > 3× monthly) was compared to the 29 coitally inactive (coitus < 10× yearly) subjects. The majority of subjects engaged in traditional sexual activities, with emphasis on physical affection and coitus. The active and inactive women were similar on all demographic variables except family income and weight/height ratio. The inactive women were slightly more obese and had lower incomes. Post-menopausal patterns of sexual activity correlated with post-menopausal sexual expression as did partner availability and function. The active women had a significantly higher LH level. No correlation was found between current or ideal sexual frequency and'androgen or estrogen levels.     

Decreased androgen concentrations and diminished general and sexual well-being in women with premature ovarian failure

OBJECTIVE: To describe general and sexual well-being in women with premature ovarian failure (POF) and to investigate whether there is a relationship between androgen levels and sexual functioning. DESIGN: Women with POF and healthy volunteers with regular menstrual cycles participated. Participants completed a written questionnaire and underwent hormonal screening. The questionnaire included standardized measures: the Questionnaire for Screening Sexual Dysfunctions, the Shortened Fatigue Questionnaire, and the Symptom Check List-90. Serum hormone measurements included estradiol, total testosterone, bioavailable testosterone, androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone sulfate. RESULTS: Eighty-one women with POF and 68 control women participated in the study. Compared with control women, women with POF reported more complaints of anxiety, depression, somatization, sensitivity, hostility, and psychological distress. Overall women with POF were less satisfied with their sexual life. They had fewer sexual fantasies and masturbated less frequently. Sexual contact was associated with less sexual arousal, reduced lubrication, and increased genital pain. However, the frequency of desire to have sexual contact and the frequency of actual sexual contact with the partner did not differ between women with POF and control women. Women with POF had lower levels of estradiol, total testosterone, and androstenedione. Multiple regression analysis revealed that androgen levels had only a weak influence on sexual functioning; higher total testosterone levels were associated with increased frequency of desire for sexual contact, and higher androstenedione levels were associated with elevated frequency of sexual contact. CONCLUSIONS: Women with POF have diminished general and sexual well-being and are less satisfied with their sexual lives than control women. Although women with POF had lower androgen levels, we did not find an important independent role for androgens in various aspects of sexual functioning.     

Abnormal steroid excretion in gestational trophoblastic disease complicated by ovarian theca-lutein cysts.

Serum and urine steroids were examined in two subjects with trophoblastic disease accompanied by large ovarian theca-lutein cysts and compared with those from 10 patients with trophoblastic disease but without palpable cysts. In the patients without cysts normal values were obtained for serum oestradiol, progesterone, 17 alpha-hydroxyprogesterone and androstenedione, and for urinary total oestrogens, pregnanediol, pregnanetriol, and 17-oxosteroids. Nineteen urinary steroid metabolites, quantified by capillary gas-liquid chromatography, were either within reference limits or marginally raised. In several cases relatively minor increases in serum testosterone and cortisol and urinary free cortisol were observed. In contrast, the subjects with cysts showed pronounced excesses of androgen metabolites, 17 alpha-hydroxypregnenolone, pregnanediol, and pregnanetriol, and both exhibited a similar pattern of unusual additional metabolites. The profiles superficially resembled those seen in 21-hydroxylase deficiency adrenogenital syndrome, but there were important discrepancies reflecting known differences in ovarian and adrenal steroid metabolism. Chemotherapy led to decline of human chorionic gonadotrophin concentrations, regression of the cysts, and return to normal of the steroid profile. Excess steroids in the patients with cysts may have originated in the ovary rather than in the trophoblastic tissue.     

Maternal serum androgens in pregnant women with polycystic ovarian syndrome: possible implications in prenatal androgenization

BACKGROUND: The aim of this study was to evaluate the peripheral serum androgen concentrations in normal and polycystic ovarian syndrome (PCOS) women during pregnancy, in order to establish if PCOS may induce gestational hyperandrogenism and therefore constitute a potential source of androgen excess for the fetus. METHODS: Twenty pregnant PCOS (PPCOS) women and 26 normal pregnant (NP) women of similar age with singleton pregnancies were selected for the study. During gestational weeks 10-16 and 22-28, a 2 h, 75 g oral glucose tolerance test (OGTT) was performed. For the OGTT, glucose and insulin were measured in each sample and testosterone, androstenedione, dehydroepiandrosterone sulphate (DHEAS), estradiol, progesterone and sex hormone-binding globulin were determined in the fasting sample. RESULTS: In the first study period (gestational weeks 10-16), the levels of androstenedione, testosterone and DHEAS and the free androgen index tended to be higher in the PCOS group. These differences became significant in the second study period (gestational weeks 22-28). In this second period, 2 h insulin concentrations were also significantly higher in PPCOS than in NP women. CONCLUSIONS: The present study demonstrates a significant increase in androgen concentrations during pregnancy in PCOS women. We propose that these androgen concentrations could provide a potential source of androgen excess for the fetus, without leading to fetal virilization.     

Effect of interferon alpha on high serum androgen concentrations in HIV positive men with Kaposi's sarcoma.

AIM: To measure serum androgen concentrations in men with HIV related Kaposi's sarcoma (KS) who had been treated with recombinant interferon (IFN) alpha-2a to determine the role of androgens on the development of KS lesions. METHODS: 32 men with HIV related KS who had been treated with IFN were studied: 24 men in complete KS remission and eight not in remission. Serum androgen concentrations were determined before, during, and after IFN treatment and correlated with clinical remission. RESULTS: All patients in complete KS remission had lower serum androgen concentrations following IFN treatment: -51% for dehydroepiandrosterone (DHEA) (p < 0.0001); -38% for DHEA sulphate (p < 0.002);-39% for androstenedione (p < 0.002); and -44% for testosterone (p < 0.007). These decreases brought the serum concentrations to about normal levels. However, IFN had varying effects on serum androgen concentrations in the men not in remission: a small decrease, a large increase in one androgen, or no change in serum androgens. CONCLUSIONS: The association between serum androgen levels and the progression or remission of HIV associated KS suggests that androgens affect the development of KS lesions. A clear understanding of the changes in the androgen environment may provide a sound basis for the development of new therapeutic strategies.