Urinary cortisol and cortisol metabolites in women with idiopathic hirsutism.

Urinary unconjugated cortisol, total 17-oxogenic steroids and cortisol metabolites (THF, allo-THF, THE, cortol and cortolone) were measured in 90 normal women and in 90 women with idiopathic hirsutism of comparable age group. After carrying out Student's "t"-test, the mean steroid excretion values in hirsute women were significantly higher than those from normal females. The results indicate that, due to stress, these hirsute women do have altered adrenocortical function, as assessed by the estimation of these corticosteroids of which urinary unconjugated cortisol was found to be the most sensitive index.     

Urinary testosterone and epitestosterone excretions in women with idiopathic hirsutism.

Urinary testosterone and epitestosterone were determined in 90 normal healthy women and in 90 women with idiopathic hirsutism, both groups aged between 16 and 46 years. Testosterone and epitestosterone excretion values were above the normal range in 27 of the 90 hirsute women (30%), and these 27 women had much more prominent hair growth than the others. When these results were statistically analysed according to the age groups or for all ages as a whole, they were found to be highly significant (P less than 0.0005). Therefore, it is concluded that the estimation of urinary testosterone and epitestosterone could be meaningfully applied to study the androgen status of hirsute women.     

Urinary dehydroepiandrosterone sulphate excretion in women with idiopathic hirsutism.

Urinary dehydroepiandrosterone sulphate (DHAS) concentration was measured as DHA in 100 non-obese females with idiopathic hirsutism, while, at the same time, a similar number of normal males and normal females, of comparable age group and with normal body weight, were also included in this study. The method applied involved hydrolysis of DHA-sulphate conjugate after boiling the urine samples, followed by ether extraction of the free steroid, evaporation of ether, Girard T separation of ketones from non-ketones, paper chromatographic separation of DHAS from 6beta-hydroxy-3,5-cycloandrostan-17-one and, finally DHAS was estimated spectrophotometrically after Zimmermann reaction. For comparison, 30 urine samples were estimated by a g.l.c. procedure and good agreement was found with the spectrophotometric method. It was necessary to purify DHAS by paper chromatography before Zimmerman reaction was carried out as, in the same 30 urine samples, DHAS was consistently being overestimated. Urinary DHAS (mg/24 h) in normal males gave a mean of: 2.5+/-0.94 (SD), range: 0.35+/-4.8; in normal females, mean: 1.3+/-0.57 (SD), range: 0.28-2.6; in hirsute females, mean: 2.1+/-1.5 (SD), range: 0.65-9.7. Of these hirsute females, 26 were above the range found in normal women and mean values were higher than those from the same number of normal females of comparable age group; this was found to be significant (P less than 0.0005). These results indicate that urinary DHAS (as DHA) estimation in women with idiopathic hirsutism is clinically useful and could be applied as an index of androgen status in these women.     

Prevalence of ultrasonography proved polycystic ovaries in North Indian women with type 2 diabetes mellitus

Background  

Polycystic ovaries (PCO) and their clinical expression (the polycystic ovary syndrome [PCOS]) as well as type 2 diabetes mellitus (T2DM) are common medical conditions linked through insulin resistance. We studied the prevalence of PCO and PCOS in women with diet and/or oral hypoglycemic treated T2DM and non-diabetic control women.     

Urinary pregnanetriol and delta 5-pregnentriol in women with idiopathic hirsutism

Urinary pregnanetriol and delta 5-pregnenetriol were determined in 90 normal women and in 90 women with idiopathic hirsutism of comparable age group. When group Student's "t"-test was carried out, the mean steroid excretion values in hirsute women were found to be significant with delta 5-pregnenetriol more significant than pregnanetriol. Of the 90 women with hirsutism, 8 patients had pregnanetriol and delta 5-pregnenetriol values higher than normal. When, on the basis of these elevated values, the women were sent for a thorough gynaecological investigation, they were found to have the polycystic ovary syndrome. After wedge resection, the diagnosis was confirmed and the urinary excretion of pregnanetriol and delta 5-pregnenetriol came down to a normal level. This study shows that, in the case of women with idiopathic hirsutism suspected of any ovarian disorder, the measurement of these two steroids could be of diagnostic importance.     

Use of LHRH agonists in the treatment of anovulation in women with polycystic ovary syndrome

The long-acting agonist analogue of LHRH, Buserelin (Hoechst) has been used to suppress endogenous gonadotrophins prior to induction of ovulation with low dose human menopausal gonadotrophin (HMG) in women with clomiphene-resistant polycystic ovary syndrome (PCOS). The results have been compared with those in a similar group of patients treated with HMG alone. Buserelin (900-1,500 micrograms/day) was given intranasally to 11 women who thereafter received a total of 33 cycles of treatment with low-dose HMG. The control group comprised 16 women who received 40 cycles of HMG without Buserelin pretreatment. The ovulation rate was similar in the two groups: Buserelin + HMG 70%, HMG alone 68% and both groups showed a high rate of single follicle ovulation (52 and 63%, respectively). The threshold dose of gonadotrophin required to induce a single follicle was similar in the two groups. Premature elevation of LH in the late follicular phase was common in women who received HMG alone, but did not occur in any cycle in the patients receiving Buserelin pretreatment. In summary, these data show that pretreatment with an LHRH analogue prevents a premature LH surge but it remains to be determined whether this will have a significant bearing on the rate of successful pregnancy in women with PCOS.     

Plasma androgens in idiopathic hirsutism

The plasma concentrations of testosterone, androstenedione,5-androstene-3β, 17β-diol, 5α-dihydrotestosterone and 17β-hydroxy-androgens have been measured in normal women and in patients with idiopathic hirsutism. The mean levels of all the compounds studied were higher in the group of patients with hirsutism than in the controls and apart from dihydrotestosterone, this difference was statistically significant. The correlation between the plasma levels of the various steroids was examined. In the normal subjects, testosterone and androstenedione levels were well correlated, but in the hirsute patients, the correlation is poor. It is suggested that this is related to altered binding of testosterone to plasma proteins in these patients. No one of the steroid levels measured was consistently abnormal in hirsutism, but in 40% of the patients, plasma androstenedione levels were above the normal range.     

Role of obesity and hyperinsulinemia in the insulin resistance of obese subjects with the clinical triad of polycystic ovaries, hirsutism and acanthosis nigricans

The insulin resistance of 4 nonobese and 8 obese patients with polycystic ovaries, hirsutism and benign acanthosis nigricans, and of 6 'obese normal' apart from obesity and 10 normal female subjects was evaluated by means of an intravenous insulin tolerance test and by measuring basal and insulin responses to an oral glucose load. The patients with polycystic ovaries, hirsutism and acanthosis had a decreased hypoglycemic response to exogenous insulin. The subjects with polycystic ovaries presented a significantly greater mean glucose response area for the same or greater mean insulin response area than the obese or nonobese normal subjects. The insulin resistance in the patient with polycystic ovaries, hirsutism and acanthosis nigricans could not be exclusively ascribed to a reduced receptor number, but also appeared to be due to a simultaneous postbinding defect probably related to the high insulin levels in patients with polycystic ovaries be they obese or not. The elevated plasma androgens and the presence of acanthosis found in these patients are likely also related to the hyperinsulinemia. To evaluate the influence of obesity, obese and nonobese patients with acanthosis nigricans and polycystic ovaries were compared. Higher insulin levels were found in the thin subjects, which could explain their greater insulin resistance and more severe hyperandrogenism. The comparison between obese patients with and those without acanthosis nigricans and polycystic ovaries suggested that, despite similar insulin levels, the greater known duration of obesity (probably also of the hyperinsulinemia) of the former was a possible explanation for their more intense insulin resistance and higher testosterone levels.     

Alterations in gonadotropin-releasing hormone-dependent gonadotropin secretion in rats with polycystic ovaries.

A single injection of estradiol valerate (EV) to adult female rats induces a persistent anovulatory polycystic ovarian (PCO) condition. During the 8-20-wk interval following EV treatment, this condition is associated with a selective compromise of LH release, decreased pituitary content of LH, and decreased GnRH-stimulated LH secretion. A marked increase in mean plasma concentrations of LH and enhanced LH response to GnRH occur after 20 wk post-EV treatment. Despite this apparent improvement, the PCO condition remains unchanged. The present study was undertaken to elucidate the underlying causes for these spontaneous improvements in LH parameters. We reasoned that these changes may be the result of alterations in 1) pituitary GnRH receptor levels; or 2) the mode of LH secretion, i.e. GnRH-dependent versus GnRH-independent; or 3) post-GnRH receptor events. Hence, we assessed pituitary GnRH receptor concentration as well as the pituitary content of LH and FSH in rats with PCO of 9 wk and 22 wk duration. To examine the possibility of a change in the mode of LH secretion, we examined the effects of in vivo suppression of LH secretion by treatment with a GnRH antagonist [N-Ac-D-Nal1, D-Phe2,3, D-Arg6, Phe7, D-Ala10]-GnRH (GnRH-ANTAG) in the same groups of animals. Mean pituitary weights were greater in the 9-wk-PCO than in the 22-wk-PCO animals. The pituitary concentration of GnRH receptors (on either a weight or milligram pituitary-membrane protein basis) was similar in the 9-wk- and 22-wk-PCO animals. Pituitary LH and FSH contents, however, were significantly higher (5-fold and 2-fold, respectively) in 22-wk-PCO rats compared to the 9-wk-PCO animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

17 beta-Hydroxysteroid oxidoreductase activity in the endometrium of normal women and patients with pelvic pain and polycystic ovaries

17 beta-Hydroxysteroid oxidoreductase (17-OHSD) activity in the endometrium of women with pelvic pain syndrome (PPS) and/or polycystic ovaries (PCO) was compared with that of a control group. In both groups there was a 10-fold increase in 17-OHSD activity in secretory phase tissue compared with that of the proliferative phase, measured by both oxidative and reduction pathways, and a highly significant correlation between the two directions (P less than 0.001). In normal subjects, the ratio of activity measured under oxidative conditions: reducing conditions, at all stages of the cycle except late proliferative phase, was 2.1-2.9. In the late proliferative phase the ratio was 5.5 which was significantly different from other stages of the cycle. Similar ratios were found for the PPS/PCO group (proliferative phase 2.5, secretory phase 5.6); these were also significantly different (P less than 0.01). On the basis of this study oestrogen metabolism in the endometrium of women with PPS and/or PCO appears to be no different from that of normal subjects. Measurement of enzyme activity in high speed soluble and particulate fractions of endometrial homogenate indicated the presence of two activities with different cofactor requirements. Gel filtration chromatography of the soluble fraction revealed a single peak of activity coincident with a molecular weight of 30 kDa with a strong preference for NAD + as cofactor. These preliminary findings suggest the presence of both soluble and particulate forms of 17-OHSD activity in the endometrium.     

Pituitary gonadotropin-releasing hormone receptor content in rats with polycystic ovaries

A single injection of estradiol valerate (EV) induces, after a lag period of 4-6 wk, a chronic anovulatory polycystic ovarian (PCO) condition in adult rats. This condition is associated with a selective compromise of luteinizing hormone (LH) release and/or synthesis reflected in low basal serum LH concentrations, decreased pituitary content of LH, and decreased gonadotropin-releasing hormone (GnRH)-stimulated LH secretion. The present study was undertaken to determine to what extent the aberrant LH release in rats with PCO could be related to alterations in pituitary content of GnRH receptors. Pituitary GnRH-receptor content was assessed by the evaluation of saturation binding of a GnRH analog, [125I]-D-Ala6-des-Gly10-GnRH, to pituitary membrane preparations. The receptor content of pituitaries from rats with PCO was compared to that obtained from intact animals at estrus and diestrus. Receptor levels in ovariectomized normal rats and rats with PCO were also assessed. The pituitary GnRH receptor content in PCO rats was similar to that observed in normal controls at estrus and was significantly lower than that for rats at diestrus. Although a twofold increase in pituitary GnRH receptor content was observed at 28 days following the castration of control rats, GnRH receptor content in the pituitaries of PCO rats, at 28 days following ovariectomy, remained unchanged. Although, castration-induced elevations in mean serum LH and follicle-stimulating hormone (FSH) concentrations were observed in both the PCO and control animals, the rise in both gonadotropins was significantly attenuated in the PCO-castrates when compared to the ovariectomized controls. Since GnRH is a major factor in the regulation of pituitary GnRH receptor content, these findings suggest that hypothalamic GnRH release is impaired in rats with PCO and that this impairment is independent of any influences from the polycystic ovaries.     

Circulating hormone concentrations in hypothyroid rats with induced polycystic ovaries

The induction of polycystic ovaries in hypothyroid rats by human chorionic gonadotropin (hCG) has been studied for many years. A complete understanding of this phenomenon requires information regarding the circulating levels of the hormones of the hypophyseal-gonadal axis. In this study, serum prolactin (PRL), luteinizing hormone (LH), estradiol, testosterone, and progesterone were measured by radioimmunoassay at intervals during the 40-day period in which large ovarian cysts were induced in hypothyroid rats by daily injections of hCG. After 20 injections, ovaries increased in weight 10-fold, and well-developed ovarian cysts were present, accompanied by lutein tissue; cyst development continued for the subsequent 20 days of hCG. Both PRL and LH rose during the first 5 days of treatment and were maintained at high levels from day 20 on. The pattern of change of gonadal steroids showed greater increases with hCG in hypothyroid than in euthyroid rats. Levels of estradiol in hypothyroid, hCG-injected rats increased in parallel to ovarian hypertrophy, whereas progesterone was high in initial stages and then declined. Testosterone increased in both euthyroid and hypothyroid animals, with no clear pattern coincident with cyst formation. The data suggest that the formation of polycystic ovaries in the hypothyroid rat is associated with high levels of PRL and LH followed by elevations of estradiol, which may serve to maintain continuous PRL, as well as LH, stimulation of the ovary.     

Lipid disturbances in women with polycystic ovary syndrome.

Small but detectable disturbances concerning blood lipid levels manifested by somewhat higher concentrations of LDL-cholesterol and triglycerides as well as higher values of atherogenic indices expressing the ratio of cholesterol present in atherogenic lipoprotein fractions to that present in atheroprotective HDL fraction have been shown to exist in 36 women with polycystic ovary syndrome. HDL-cholesterol concentration was lower in women with polycystic ovary syndrome than in healthy women. The disturbances described above were more pronounced in obese patients. No correlation was found between the disturbances in lipid levels and hormonal disturbances particularly hyperandrogenemia.     

Twenty-four-hour serum growth hormone, insulin, C-peptide and blood glucose profiles and serum insulin-like growth factor-I concentrations in women with polycystic ovaries.

Raised insulin levels are now recognized as a characteristic feature of women with polycystic ovaries (PCO), and hyperinsulinism has been shown to stimulate androgen production in such women. We have, however, recently shown that hyperinsulinaemia is present only in the obese subjects with PCO in whom insulin concentrations correlate with those of luteinizing hormone. We therefore studied 24-hour blood profiles of growth hormone (GH) and insulin-like growth factor-I (IGF-I) in obese and non-obese women with PCO, for comparison with their levels of insulin, C-peptide and other hormones, such as androgens which are known to be disturbed in PCO. Mean 24-hour GH levels were higher overall in PCO than in control subjects, although the difference was not significant. When, however, a separate analysis was made in obese as compared with non-obese PCO patients, GH concentrations were significantly higher in the non-obese group than in the obese (p = 0.0005). There was a significant negative correlation between body mass index and mean 24-hour GH concentrations (r = -0.641; p = 0.0006). IGF-I concentrations were however similar in the PCO group overall and in controls, as well as in the obese and non-obese PCO patients. The 24-hour blood glucose profile pattern was significantly different in PCO women from controls (p = 0.009), with absence of post-prandial peaks in blood glucose concentrations. These changes were most marked in the non-obese PCO group, who also had significantly lower blood glucose levels than either controls or obese PCO subjects.(ABSTRACT TRUNCATED AT 250 WORDS)