androstane-3-17-diol-glucuronide and Hirsutism

Topics: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase; Androgens; Androstane-3,17-diol; Androstanols; Dihydrotestosterone; Female; Hirsutism; Humans; Skin; Testosterone

Assay by ultrasensitive methods of serum prostate-specific antigen (PSA) recently demonstrated that many women have detectable levels of this molecule. Interestingly, serum PSA concentrations were higher in hirsute than in nonhirsute subjects, suggesting that, also in females, PSA may be regulated by androgens. To establish the potential for this assay as a biochemical marker of androgen action in women, we studied 40 hirsute subjects recruited in a double-blind, placebo-controlled, 6-month trial assessing the effects of 3 different antiandrogen drugs: spironolactone, flutamide, or finasteride. In each subject, serum PSA, free testosterone, and 3alpha-androstanediol glucuronide were determined at baseline and at the end of treatments. At baseline, PSA concentrations were higher in these 40 women than in 19 nonhirsute healthy controls (12.9+/-1.5 vs. 4.9+/-0.7 pg/mL, P = 0.03) and significantly correlated with serum free testosterone (r = 0.37, P<0.005). After treatments, the 29 hirsute subjects given active drugs showed significant reduction of serum PSA levels (7.2+/-1.4 vs. 14.7+/-3.0 pg/mL, P = 0.002). This phenomenon was correlated to baseline PSA values. No change was found in the placebo group. In conclusion, serum PSA is increased in many hirsute women. A 6-month course of antiandrogen treatments with spironolactone, flutamide, or finasteride determines a reduction of PSA levels in these subjects. These results suggest that serum PSA is a biochemical marker of androgen action in tissues of female subjects.

Topics: Adult; Androgen Antagonists; Androgens; Androstane-3,17-diol; Biomarkers; Double-Blind Method; Enzyme Inhibitors; Female; Finasteride; Flutamide; Hirsutism; Humans; Prostate-Specific Antigen; Spironolactone; Testosterone

To compare the effectiveness of finasteride and flutamide in the treatment of idiopathic hirsutism.. Randomized study.. Department of Gynecological Endocrinology, University of Brescia, Italy.. Forty-six women with idiopathic hirsutism were selected.. Patients were assigned randomly to receive 5 mg of finasteride once daily or 250 mg of flutamide twice daily for 12 consecutive months.. Hirsutism was evaluated at 6 and 12 months of therapy by measuring the Ferriman-Gallwey score and the terminal-hair diameters (microm) taken from different body areas. Blood samples were taken and side effects were monitored during the treatment.. Both finasteride and flutamide induced a statistically significant decrease in hirsutism scores and hair diameters at the end of 12 months. Finasteride reduced the Ferriman-Gallwey score by 20.5% at 6 months and by 34.2% at 12 months, and hair diameter by 18.9%-23.6% at 6 months and by 29.6%-37.9% at 12 months. Flutamide reduced the Ferriman-Gallwey score by 26.6% at 6 months and by 50.9% at 12 months, and hair diameter by 22.3%-28.2% at 6 months and by 47.7%-56.5% at 12 months. Flutamide did not induce hormonal variations, whereas finasteride increased T levels by 60% and decreased 3alpha-androstanediol glucuronide by 69.5% at 12 months.. Both drugs were effective in the treatment of idiopathic hirsutism, but flutamide was more effective than finasteride.

Topics: Adolescent; Adult; Androgen Antagonists; Androstane-3,17-diol; Body Mass Index; Enzyme Inhibitors; Female; Finasteride; Flutamide; Hair; Hirsutism; Humans; Testosterone; Treatment Outcome

The effect of peripheral androgen hypersensitivity on bone mineral density (BMD) was investigated in a group of adolescent women with idiopathic hirsutism (n = 17; mean age 17.0 +/- 1.7 years). The effect of long-term androgen-receptor blockade with flutamide (500 mg daily in two divided doses for 12 months) on BMD was assessed too. BMD was measured at lumbar spine (L2-L4) by a dual energy X-ray densitometer. Before flutamide treatment, patient BMD (1.14 +/- 0.07 g/cm2) was not significantly different from that of the control group (1.16 +/- 0.12 g/cm2, n = 22), and was normal for age and sex (BMD 0.14 +/- 0.69 SDS, P = NS vs. 0). After 12 months of treatment, absolute BMD in patients increased (1.18 +/- 0.08 g/cm2, P < 0.002), but SDS BMD did not change (0.21 +/- 0.72, P = NS vs. baseline). Flutamide treatment determined a clinical, marked improvement of androgen hypersensitivity (Ferriman-Gallwey score: before 22.0 +/- 6.2; 6 months: 13.2 +/- 6.4, P < 0.003; 12 months; 7.6 +/- 4.1, P < 0. 001; acne score: before 3.8 +/- 0.8; 3 months 0.8 +/- 0.5, P < 0. 001; later disappeared). The serum levels of 3alpha-androstenediol-glucoronide decreased (before: 8.6 +/- 1.1 microg/liter; 12 months: 7.2 +/- 1.0 microg/liter, P < 0.02), whereas the other endocrinological parameters did not change. No relationship was found between BMD and clinical or biochemical parameters of hyperandrogenism. We concluded that in adolescent women, peripheral hyperandrogenism is not associated with abnormal BMD; long-term treatment with flutamide, which blocks the androgen receptor, does not alter their BMD.

Topics: Absorptiometry, Photon; Acne Vulgaris; Adolescent; Adult; Analysis of Variance; Androgen Antagonists; Androgen Receptor Antagonists; Androstane-3,17-diol; Bone Density; Dehydroepiandrosterone; Female; Flutamide; Follicle Stimulating Hormone; Hirsutism; Humans; Lumbar Vertebrae; Luteinizing Hormone; Sex Hormone-Binding Globulin

To evaluate the long-term efficacy of the 5 alpha-reductase inhibitor finasteride in idiopathic hirsutism.. Prospective clinical study.. Outpatients in a university hospital.. Fourteen young women with idiopathic hirsutism.. Finasteride, 5 mg once daily, was given for 12 months.. Degree of hirsutism, graded by a modified Ferriman and Gallwey score, serum sex hormones, and serum and urinary markers of 5 alpha-reductase activity. Clinical outcome was evaluated up to and including the 1-year post-treatment period.. The Ferriman and Gallwey score showed a remarkable reduction after 12 months of finasteride treatment (4.4 +/- 0.7 versus 11.8 +/- 1.0; mean +/- SEM). Serum levels of the two 5 alpha-reductase activity markers, dihydrotestosterone and 3 alpha-androstanediol glucuronide, decreased, and urinary C19 and C21 5 beta:5 alpha steroid metabolite ratios consistently increased during finasteride administration. These changes were reversed readily after cessation of treatment. No significant adverse effect was reported. Nine of 14 women completed the 1-year post-treatment follow-up. Their hirsutism scores were increased substantially as compared with values recorded at the end of therapy, but still were lower than baseline values.. The 5 alpha-reductase inhibitor finasteride is effective and well tolerated in longterm treatment of women with idiopathic hirsutism. Post-treatment follow-up suggests that drug effects on hair growth are sustained in the majority of subjects with this disorder.

Topics: 5-alpha Reductase Inhibitors; Adult; Androstane-3,17-diol; Dihydrotestosterone; Enzyme Inhibitors; Female; Finasteride; Hirsutism; Humans; Luteinizing Hormone; Testosterone; Treatment Outcome

Fifty-one hirsute women were randomly treated for nine months with ethinyl estradiol 35 ug plus norethindrone 0.4 mg or 30 ug ethinyl estradiol plus 1.5 mg norethindrone acetate if they needed contraception or spironolactone 200 mg daily if they did not. Metabolic evaluations in response to therapy demonstrated triglyceride elevations with the two oral contraceptives but not with spironolactone. While systolic blood pressure was lower with spironolactone, fasting insulin levels were higher as opposed to either low-dose oral contraceptive preparation. Ethinyl estradiol 30 ug plus 1.5 mg norethindrone acetate lowered 3-alpha-diol glucuronide levels, yet ethinyl estradiol 35 ug plus norethindrone 0.4 mg and spironolactone were more effective in lowering Ferriman-Gallwey Scores. Treatment strategies for hirsute women need to consider metabolic consequences as well as efficacy.. 51 hirsute women were randomly treated for 9 months with ethinyl estradiol (EE) 35 mcg + norethindrone 0.4 mg or 30 mcg EE + 1.5 mg norethindrone acetate if contraception was necessary or spironolactone 200 mg daily if it was not. Metabolic evaluations in response to therapy demonstrated triglyceride elevations with the 2 oral contraceptives (OCs) but not with spironolactone. While systolic blood pressure was lower with it, fasting insulin levels were higher as opposed to either low-dose OC preparation. EE 30 mcg + 1.5 mg norethindrone acetate lowered 3-alpha-diol-glucuronide levels; however, E 35 mcg + norethindrone 0.4 mg and spironolactone were more effective in lowering Ferriman-Gallwey scores. Treatment strategies for hirsute women need to consider metabolic consequences as well as efficacy.

Topics: Analysis of Variance; Androstane-3,17-diol; Blood Pressure; Body Weight; Cholesterol, HDL; Ethinyl Estradiol; Female; Hirsutism; Humans; Insulin; Norethindrone; Spironolactone; Testosterone

Dose-dependent hypertrichosis is a common dermatological side-effect affecting the majority of patients treated with cyclosporine A (CSA). Previous studies have not demonstrated the influence of CSA on specific sex hormone levels. The aim of this study is to investigate whether CSA increases the activity of 5 alpha-reductase, an enzyme which transforms androgens into dihydrotestosterone in peripheral tissues. The metabolite which best reflects this activity is 5 alpha-androstane-3 alpha,17 beta-diol glucuronide (Adiol G). The study was carried out on 49 insulin-dependent diabetes patients participating in the double-blind "Cyclosporine-Diabète-France" clinical trial, of which 28 were treated with CSA (16 males and 12 females), and 21 received only placebo (10 males and 11 females). All patients underwent extensive clinical and laboratory evaluations prior to and during the present study. In addition to Adiol G, testosterone (T), dehydroepiandrosterone sulfate (DHEA S) and sex hormone-binding globulin (SHBG) were assayed. Levels of Adiol G increased significantly in CSA-treated groups: males, 11.86 +/- 2.58 vs 7.83 +/- 2.30 nmol/l; females, 4.48 +/- 2.70 vs 2.10 +/- 1.22 nmol/l; P less than 0.02 (comparison of means). There were no significant differences in this parameter before and during treatment in either the male or female placebo groups (paired t-test). During the treatment period, T, DHEA S, SHBG and the T/SHBG ratio did not significantly change with respect to their baseline values in any of the groups studied (comparison of means). Comparison (using paired t-test) showed a significant increase of DHEA S in CSA-treated groups: males, delta = 3.08 +/- 3.33 nmol/l, P less than 0.01; females, delta = 0.98 +/- 1.13 nmol/l, P less than 0.05. In conclusion, it is possible that CSA induces hypertrichosis or hirsutism by increasing 5 alpha-reductase activity in peripheral tissues. Nevertheless the role of increased DHEA S as a possible Adiol G precursor cannot be excluded.

Topics: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase; Androstane-3,17-diol; Androstanols; Cyclosporins; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Diabetes Mellitus, Type 1; Female; Hirsutism; Humans; Male; Prospective Studies; Sex Hormone-Binding Globulin; Testosterone

Acne in adult women is a frequent hard-to-manage disease with many relapse cases. It mostly interferes with the quality of life of patients, bringing them major metabolic and social losses. As androgenic hormones play a very important role in the acne pathogenesis, the early diagnosis of hyperandrogenic states is very useful for the proper evaluation of each patient and for a better choice of therapeutic management. Defining a pattern for laboratory profile analysis is important for the control of relapses of acne breakouts in adult women, which lately has been the aim of many published studies.. To establish the relation between 3 alpha-diol G levels and acne in female patients with normal androgenic status without menstrual dysfunctions.. The evaluation of serum 3 alpha-androstanediol glucuronide levels through an enzymatic immunoassay method (Androstanediol Glucuronide ELISA Kit) for a direct quantitative measurement in 26 patients with grade II and III acne, ages ranging from 13 to 50.. Among the analyzed patients, 83% had grade II acne, and among this total, 60% were aged 14 or over. According to age, 12 studied patients showed serum 3 alpha-diol G levels within normal range and 11 patients had increased levels.. A total of 60% of adult women with acne present increased levels of androgens and among those with normal levels and without menstrual dysfunctions, 50% show an increase in 3 alpha-diol G. Therefore, a pharmacological approach with anti-androgenic drugs for acne therapy in most of these patients is advisable.

Topics: Acne Vulgaris; Adolescent; Adult; Age Factors; Androstane-3,17-diol; Biomarkers; Cholestenone 5 alpha-Reductase; Hirsutism; Humans; Prospective Studies; Puberty; Severity of Illness Index; Young Adult

The study objective was to assess the role of 3alpha-androstanediol glucuronide (3alpha-diolG) as the marker of peripheral androgen action in the young women with hirsutism diagnosed as polycystic ovary syndrome (PCOS), in patients with idiopathic hirsutism (IH) and in normal non-hirsute women.. Fifty-nine young women with mean age 21.90+/-3.52 years suffered from hirsutism were included in the study. Among these 59 hirsute women 31 women with mean age 21.60+/-3.56 years were diagnosed as PCOS and 28 women with mean age 22.20+/-3.59 years were classified as idiopathic hirsutism patients. Twenty-seven normal women, age-matched (mean age 22.60+/-2.90 years), without signs of hirsutism and with normal menstrual cycle served as control for this study. Serum was collected from women with hirsutism (due to PCOS or idiopathic hirsutism) and from non-hirsute women. Serum levels of 3alpha-androstanediol glucuronide (3alpha-diolG), main androgens such as: testosterone, free testosterone, dehydroepiandrosterone (DHEAS) and also others hormones such as follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and sex hormone-binding globuline (SHBG) were measured using radioimmunoassay (RIA) method in the study and control group. Hirutism was assessed using modified Ferriman-Gallwey method. Serum 3alpha-diolG levels in PCOS women were significantly higher than in controls.. There were no significant differences between serum 3alpha-diolG levels in PCOS group and IH group. Similarly, there were significant differences between serum 3alpha-diolG levels in IH group and control subjects.. We conclude that 3alpha-diolG is not useful as the marker for peripheral androgen metabolism and for differentiation between idiopathic hirsutism and PCO-related hirsutism.

Topics: Adolescent; Adult; Androstane-3,17-diol; Biomarkers; Body Mass Index; Case-Control Studies; Female; Hirsutism; Humans; Polycystic Ovary Syndrome; Testosterone

This study has evaluated the behaviour of 3alpha-androstanediol glucuronide (3alpha-diol G) in 170 women of whom 85 had polycystic ovary syndrome (PCOS), 35 had idiopathic hirsutism (IH) and 50 had regular cycles (control group). Of the women with PCOS, 45 were hirsute (PCOS-H) and 40 were non hirsute (PCOS-NH). Women in the control group were not hirsute. Hirsutism was assessed by the same physician using the Ferriman-Gallway score. The body mass index (BMI) was estimated in all of the women. Plasma concentrations of 3alpha-diol G were elevated only in hirsute patients, both with PCOS and with IH. Even in PCOS-NH, concentrations of 3alpha-diol G were higher compared with controls (P < 0.001), but significantly lower (P < 0.001) than those of the PCOS-H and of the IH groups. The behaviour of 3alpha-diol G was not affected by BMI.

Topics: Adolescent; Adult; Androstane-3,17-diol; Case-Control Studies; Female; Hirsutism; Humans; Hyperandrogenism; Obesity; Polycystic Ovary Syndrome

Prostate-specific antigen (PSA) is present at very low concentrations in female serum, but it can now be measured with highly sensitive immunoassays. We have found that in female tissues the PSA gene is regulated by steroid hormones through the action of steroid hormone receptors. Thus, we examined whether female serum PSA is associated with hyperandrogenic states. Serum PSA levels were compared between 22 hirsute women with a Ferriman-Gallwey score higher than 8 and 50 women without hirsutism. The results show that PSA levels were higher in hirsute women in comparison with controls. In hirsute women, levels of PSA and 3 alpha-androstanediol glucuronide (3 alpha-AG), a specific metabolite of androgen action, showed a significant positive correlation, whereas PSA and 3 alpha-AG showed a significant negative correlation with patient age. Receiver operating characteristic (ROC) analysis revealed that 3 alpha-AG was a slightly better marker of androgen excess than PSA. We conclude that female serum PSA may be a new biochemical marker of androgen action in females.

Topics: Adolescent; Adult; Aging; Androgens; Androstane-3,17-diol; Biomarkers; Female; Hirsutism; Humans; Middle Aged; Obesity; Prostate-Specific Antigen; Reference Values; Testosterone

Aim of this prospective diagnostic study was to determine the serum 3 alpha-androstanediol-glucuronide (AdiolG) level in hirsute women in order to assess the androgenic activity in peripheral tissue and to differentiate between hirsutism of peripheral origin and that of adrenal or ovarian origin. Diagnostic advantages might have been expected in patients with idiopathic hirsutism, in whom increased 5 alpha-reductase activity may be reflected by this parameter. Apart from serum AdiolG, we determined the established parameters testosterone, androstendione and dehydroepiandosterone sulfate in 63 hirsute premenopausal women and in 51 non-hirsute controls. AdiolG (P < 0.05), as well as the 3 established parameters (P < 0.001) were elevated in the hirsute women as compared with the controls; however, the subgroup of women with idiopathic hirsutism (n = 32) showed no elevation of serum AdiolG. Analysis of the combined hirsute and control groups showed that the correlation of AdiolG to the hirsutism score (r = 0.42) was markedly weaker than that of testosterone to the latter (r = 0.62). Moreover, no correlation was found between the body-mass index and AdiolG. Our data show that serum AdiolG is obviously not a specific marker for peripheral 5 alpha-reductase activity, but appears to reflect the adrenal and ovarian androgen precursors. Thus, determination of serum AdiolG is of no diagnostic benefit in the clinical assessment of hirsute women.

Topics: Adolescent; Adult; Androgens; Androstane-3,17-diol; Body Mass Index; Diagnosis, Differential; Female; Hirsutism; Humans; Prospective Studies; Treatment Outcome

We investigated the developmental patterns of 5 alpha-androstane-3 alpha, 17 beta-diol (AD) and 5 alpha-androstane-3 alpha, 17 beta-diol-glucuronide (ADG) in plasma of normal children and adults of both sexes and in patients with idiopathic hirsutism using a physicochemical method: high-resolution gas chromatography/mass spectrometry (HRGC/MS). In children below the age of 11 years, AD and ADG increased with age showing no differences between sexes (mean +/- SD, nmol/l): normal subjects 3-6 years: AD in females 0.08 +/- 0.03, in males 0.07 +/- 0.03; ADG in females 0.15 +/- 0.05, in males 0.14 +/- 0.04; normal subjects 7-10 years; AD in females 0.17 +/- 0.03, in males 0.17 +/- 0.07; ADG in females 0.59 +/- 0.12, in males 0.47 +/- 0.14. Thereafter, AD and ADG showed a greater increase in males (normal subjects 11-15 years: AD in females 0.24 +/- 0.06, in males 0.41 +/- 0.14; ADG in females 1.47 +/- 0.36, in males 3.36 +/- 1.22). In adults, plasma levels did not overlap between females and males (AD in females 0.24 +/- 0.07, in males 0.99 +/- 0.31; ADG in females 2.32 +/- 0.68, in males 13.01 +/- 3.05). 5 alpha-Androstane-3 alpha, 17 beta-diol-glucuronide discriminated better between sexes than AD. In idiopathic hirsutism, mean plasma concentrations of AD and ADG were higher than those of healthy females (ages 11-15 years: AD 0.31 +/- 0.10, ADG 3.48 +/- 2.00; ages > 16 years: AD 0.44 +/- 0.27, ADG 6.46 +/- 3.11), but 54% of patients had normal plasma concentrations of AD and 29% had normal ADG values. Thus, ADG reflected androgenicity better than AD. However, both metabolites were imperfect markers of androgenicity in idiopathic hirsutism. Therefore, our findings do not support the concept of increased 5 alpha-reductase activity in all patients with idiopathic hirsutism.

Topics: Adolescent; Adult; Aging; Androstane-3,17-diol; Child; Child, Preschool; Female; Gas Chromatography-Mass Spectrometry; Hirsutism; Humans; Male; Osmolar Concentration; Reference Values; Sex Characteristics

To compare the peripheral versus the splanchnic contribution to the formation of 3 alpha-diol G.. Prospective study in various groups of women and men.. Reproductive Endocrine service of our University Medical Center.. Six normal ovulatory women, five hirsute women with polycystic ovary syndrome, and six normal men.. All subjects received IV dihydrotestosterone (DHT) infusions as well as percutaneous administration of DHT. Serum was obtained at multiple time points before and after each administration of DHT.. Comparison of serum levels of DHT, 3 alpha-androstanediol (3 alpha-diol), 3 alpha-diol G, and androsterone glucuronide in the three groups.. Steady-state levels of DHT were similar in the three groups and were also similar after the two different routes of administration. However, ratios of 3 alpha-diol G to DHT were significantly greater after percutaneous gel than after IV administration in all three groups. This also was the case for the ratio of unconjugated serum 3 alpha-diol to DHT. Levels of androsterone glucuronide were similar with the different routes of administration.. Using normal routes of administration and, in attempting to assess in vivo metabolism of DHT, our data confirm that the skin is the major site of unconjugated 3 alpha-diol and 3 alpha-diol G formation. Serum 3 alpha-diol G, therefore, appears largely to reflect skin DHT metabolism.

Topics: Administration, Cutaneous; Adolescent; Adult; Androstane-3,17-diol; Androsterone; Dihydrotestosterone; Female; Hirsutism; Humans; Infusions, Intravenous; Male; Middle Aged; Polycystic Ovary Syndrome; Prospective Studies; Reference Values; Splanchnic Circulation

Serum C19 conjugates, specifically 3 alpha-androstanediol glucuronide (3 alpha G), reflect peripheral androgen action through the action of 5 alpha-reductase activity. The origin of 5 alpha-reduced C19 conjugates has been controversial and it has been suggested that they are derived primarily from adrenal androgens. We examined concentrations of 3 alpha G, 3 alpha-androstanediol sulphate (3 alpha S), androsterone glucuronide (AoG) and androsterone sulphate (AoS) in 40 hirsute hyperandrogenic women. These patients were divided into four groups based upon individual, combined or normal concentrations of the adrenal androgens dehydroepiandrosterone (DHEAS) and 11 beta-hydroxy-androstenedione. Testosterone, unbound testosterone and androstenedione were similar in these groups. Serum 3 alpha G was equally high in all groups and was correlated significantly with hirsutism, while the other conjugates were not. Androsterone glucuronide was raised in all groups but was higher in patients with raised DHEAS. Serum 3 alpha S was raised in all groups and was higher where both adrenal androgens were raised. Serum AoS was highly correlated with DHEAS. Serum 3 alpha G was correlated with unbound testosterone and androstenedione but not with the adrenal androgens. The glucuronide conjugates were correlated with one another as were the sulphate conjugates but glucuronides and sulphates were not correlated. These data confirm ovarian and adrenal dependency of C19 conjugates. Serum 3 alpha G appears to reflect hirsutism most accurately and is least dependent on adrenal androgens in patients with mixed hyperandrogenism.

Topics: Adrenal Glands; Adult; Androgens; Androstane-3,17-diol; Androsterone; Female; Hirsutism; Humans; Hyperandrogenism; Substrate Specificity

The clinical utility of serum 3 alpha-androstanediol glucuronide level has been controversial. Among the concerns regarding its lack of utility has been the finding that suppression of serum 3 alpha-androstanediol glucuronide does not occur readily with treatment. We hypothesized that because the treatment of hirsutism requires a prolonged duration, a longer observation period is required for changes in serum 3 alpha-androstanediol glucuronide to be measured. Therefore, we studied the clinical and hormonal changes in 11 women treated for hirsutism with a gonadotropin-releasing hormone agonist (GnRH-a) for 1 year. A progressive reduction in Ferriman-Gallwey scores occurred, which was significant at 6 weeks and was maximal at 12 months. Serum 3 alpha-androstanediol glucuronide and another peripheral marker, androsterone glucuronide, also fell commensurately. While there was no correlation at 3 months, by 6 weeks a significant correlation had occurred between the suppression in Ferriman-Gallwey scores and the suppression of serum 3 alpha-androstanediol glucuronide and androsterone glucuronide. The suppression of these steroids also correlated with the suppression of non-sex hormone-binding globulin-bound testosterone. These data confirm that markers of peripheral androgen action, particularly serum 3 alpha-androstanediol glucuronide, reflect the clinical manifestation of hirsutism. However, it appears that modifications in peripheral androgen activity (presumably through 5 alpha-reductase activity) are time-dependent, and that serum markers reflect changes after 6 months of treatment.

Topics: Adult; Androstane-3,17-diol; Androsterone; Female; Hirsutism; Humans; Polycystic Ovary Syndrome; Testosterone; Triptorelin Pamoate

A biochemical parameter correlating with the clinical assessment of the severity of hirsutism and changing appropriately with the clinical response to treatment would be extremely useful. Preliminary reports of androstanediol glucuronide indicated that it was a peripherally-derived androgen and had a high correlation with clinical gradings of hirsutism. More recent reports have cast doubts on this association. This paper presents an evaluation of the clinical usefulness of androstanediol in 121 consecutive premenopausal patients with hirsutism. Androstanediol had a positive correlation with the clinical grading of hirsutism (p < 0.02) and the BMI (p < 0.01) but a negative correlation with age (p < 0.01). After adjustment for the effects of age and BMI there was no significant association between the degree of hirsutism and the level of androstanediol.

Topics: Adolescent; Adult; Androstane-3,17-diol; Biomarkers; Child; Female; Hirsutism; Humans; Middle Aged; Premenopause

To determine the serum levels of androstanediol glucuronide (3 alpha-diol G), total T, and free T in hirsute and nonhirsute women.. Controlled clinical study.. Hirsute women with oligomenorrhea, hirsute women with regular ovulatory cycles, and nonhirsute women with regular cycles were selected.. Serum levels of 3 alpha-diol G, total T, and free T were measured in 8 hirsute with oligomenorrhea and 11 hirsute women with regular ovulatory cycles and compared with 20 nonhirsute women with regular cycles (control group). Serum 3 alpha-diol G was also measured during the follicular, periovulatory, and luteal phases in hirsute women with regular cycles.. Serum levels of 3 alpha-diol G did not change during the menstrual cycle, in addition we observed that there was no difference between the levels of 3 alpha-diol G, total T, and free T in hirsute women with regular cycles when compared with normal women. These three serum androgens were elevated only in the hirsute women with oligomenorrhea. Besides, there was better correlation between total T and free T (r = 0.81) than total T and 3 alpha-diol G (r = 0.49) or free T and 3 alpha-diol G (r = 0.66).. The findings suggest that serum 3 alpha-diol G does not provide additional benefit as a marker of hirsutism than serum total or free T.

Topics: Adolescent; Adult; Androstane-3,17-diol; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Follicle Stimulating Hormone; Hirsutism; Humans; Luteinizing Hormone; Menstrual Cycle; Testosterone

An oral 5-mg dose of finasteride, a 5 alpha-reductase inhibitor, was administered for 3 months to 10 hirsute women to determine the effect on gonadotropin secretion, on basal and stimulated androgen secretion, and on hair growth. Hair growth was assessed by the Ferriman-Gallwey score. All of the above determinations were evaluated before and after 1 and/or 3 months of finasteride treatment. Basal and GnRH-stimulated gonadotropin secretions were not affected. Indeed, finasteride did not modify the pulsatility of LH secretion. No change was seen in estradiol, PRL, free testosterone, androstenedione, dehydroepiandrosterone sulfate, and sex hormone-binding globulin concentrations. Serum concentrations of cortisol (F) were significantly reduced after 1 month of finasteride treatment. The F levels returned to pretreatment levels after 3 months. Plasma levels of dihydrotestosterone and 3 alpha-androstanediol glucuronide significantly decreased during finasteride treatment. A significant increase in testosterone concentrations was observed after 3 months. Finasteride did not modify the responses of testosterone, androstenedione, and dehydroepiandrosterone sulfate to ACTH-(1-24) injection. Conversely, finasteride blunted the F response to corticotropin stimulation. Three months of finasteride treatment significantly decreased the Ferriman-Gallwey score. In conclusion, finasteride significantly decreased dihydrotestosterone and hair growth in hirsute women without negatively affecting gonadotropin secretion.

Topics: 5-alpha Reductase Inhibitors; Adolescent; Adult; Androgens; Androstane-3,17-diol; Cosyntropin; Dihydrotestosterone; Female; Finasteride; Follicle Stimulating Hormone; Hair; Hirsutism; Humans; Hydrocortisone; Luteinizing Hormone; Periodicity; Testosterone

Recent evidence suggests that androstanediol glucuronide (AG), a metabolite of dihydrotestosterone (DHT) formed in skin, is frequently elevated in hirsute women, presumably reflecting enhanced 5 alpha-reductase activity. An alternative method of demonstrating 5 alpha-reductase activity is the androsterone (A)/aetiocholanolone (E) ratio in urine. A and E are the 5 alpha- and 5 beta-reduced metabolites, respectively, of androstenedione, which is the principal metabolite of dehydroepiandrosterone (D). Although serum AG and the urinary A/E ratio have both been considered valid methods for assessing 5 alpha-reductase activity, the two have not been previously compared in hirsute women. The present study was undertaken to assess 5 alpha-reductase activity in hirsute patients as determined by these two different methods.. We surveyed 47 untreated women (ages 17-33) with various degrees of hirsutism. Serum testosterone, bioavailable testosterone, dehydroepiandrosterone sulphate, and AG were determined. Additionally, A, E and D were measured in 24-hour collections of urine.. For the 47 women, 37 had elevated blood levels of AG (17.4 +/- 2.2, mean +/- SEM; normal < 8 nmol/l), but only 18 of these had an increased urinary A/E ratio (> 1.5). All but one of the remainder had elevated urinary and/or serum androgen levels. Overall, no significant correlation between AG and A/E was observed. There was a highly significant correlation between AG in serum and A in urine (r = 0.82, P < 0.001). AG was also positively related to dehydroepiandrosterone sulphate (r = 0.64; P < 0.005), bioavailable testosterone (r = 0.6; P < 0.001), aetiocholanolone (r = 0.58; P < 0.001) and total testosterone (r = 0.52; P < 0.01). In contrast, A/E was not significantly related to androgen production.. There is a poor correlation between AG and the A/E ratio in hirsute women. Although AG may be raised by increased 5 alpha-reductase activity, it is probably also affected by the presence of elevated androgens regardless of 5 alpha-reductase activity.

Topics: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase; Adolescent; Adult; Androstane-3,17-diol; Androstanols; Androsterone; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Etiocholanolone; Female; Hirsutism; Humans; Testosterone

Acne is one of the most common skin disorders. Androgens are known to play an important and possibly central role. Androgens secreted from ovaries and adrenal glands (androstenedione, dehydroepiandrosterone and its sulphate, testosterone) and target tissue-produced androgens (testosterone and its 5 alpha-reduced metabolite, dihydrotestosterone) have been implicated. Although the sebaceous gland and the hair follicle form a single morphological entity, the pilosebaceous unit, acne and hirsutism do not always appear concomitantly, thus leading to the supposition that these two structures may have different degrees of sensitivity to similar androgenic stimulation.. To determine whether acne and hirsutism are the clinical expression of a different androgen metabolism at target tissue levels we studied 90 randomly selected patients who came to our Out-patient Department for diagnosis and treatment during the last 2 years with isolated acne of mild to severe degree and 52 patients with idiopathic hirsutism without acne or history of acne. Twenty-four women without acne or hirsutism and without a history of endocrine disease were studied as controls.. In both groups of patients, plasma levels of sex hormone binding globulin, of dihydrotestosterone, and of 3 alpha-androstanediol and of its glucuronide were evaluated. In all patients the percentage of free testosterone and the testosterone/sex hormone binding globulin ratio were also calculated.. Patients with acne and those with isolated hirsutism showed significantly decreased sex hormone binding globulin plasma levels. The values of the percentage free testosterone and those of the testosterone/sex hormone binding globulin ratio were, on the contrary, higher with respect to the controls, although there were no statistically significant differences between the two groups. Significantly increased plasma levels of dihydrotestosterone with respect to the controls were observed in patients with acne or in those with hirsutism. However, while all patients with hirsutism showed increased plasma values of 3 alpha-androstanediol and its glucuronide, all patients with acne showed plasma levels within the normal range, independently of the precursor plasma levels.. Our results demonstrate that dihydrotestosterone is further reduced to 3 alpha-androstanediol and its glucuronide only in hirsute patients but not in acne patients. These results suggest that dihydrotestosterone may undergo different metabolic pathways at skin levels and support the hypothesis that the two clinical manifestations may be the expression of the different metabolic fate of dihydrotestosterone itself. Moreover, our results demonstrate that 3 alpha-androstanediol and its glucuronide cannot be used as plasma markers of target-tissue produced androgens in all hyperandrogenic conditions.

Topics: Acne Vulgaris; Adolescent; Adult; Androstane-3,17-diol; Dihydrotestosterone; Female; Hair; Hirsutism; Humans; Sebaceous Glands; Sex Hormone-Binding Globulin; Testosterone

3 alpha, 17 beta-androstanediol-glucuronide (Adiol-G) has been described as a marker of local androgen excess due to the increased activity of 5 alpha-reductase in the cells of the hair follicles. In order to test the diagnostic value of Adiol-G, the serum level was compared to that of testosterone, free testosterone, dehydroepiandrosterone sulfate (DHEA-S), androstenedione and to the body mass index in 44 women with androgenic symptoms (Group I), 27 women with menstrual disturbances but no androgenic symptoms (Group II), and 48 healthy women (Group III) who served as controls. Adiol-G was significantly higher (7.8 +/- 5.1 nmol/l) in women with androgenic symptoms than in the other groups, but there was a considerable overlap. Serum testosterone was also found to be higher in Group I than in Groups II and III, respectively. There was a significant correlation between Adiol-G and testosterone, and Adiol-G and DHEA-S. No significant correlation could be shown to exist between androstenedione and Adiol-G. When Adiol-G and testosterone were simply classified as 'normal' or 'increased' (Adiol-G 9.4 nmol/l; testosterone greater than 2.4 nmol/l), higher than normal values of the former were found in the presence of normal testosterone in only 4% of the cases. It is concluded that the level of Adiol-G generally parallels that of testosterone. Consequently, it does not seem to be an effective marker of peripheral androgen excess.

Topics: Acne Vulgaris; Adolescent; Adult; Alopecia; Androgens; Androstane-3,17-diol; Biomarkers; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Hirsutism; Humans; Middle Aged; Oligomenorrhea; Testosterone

The aim of the study was to investigate whether the absence of increased 5 alpha-reductase activity explained the absence of hirsutism in premenopausal obese women with increased free testosterone (FT) levels.. As in hyperandrogenicity there generally exists evidence for increased 5 alpha-reductase activity, we measured, as parameters of 5 alpha-reductase activity, plasma levels of 5 alpha-androstane-3 alpha,17 beta-diol glucuronide (ADG) and androsterone glucuronide (ADTG) as well as their precursor levels in obese women without hirsutism, obese hirsute women, non-obese hirsute women, and non-obese, non-hirsute women.. Eighty-two premenopausal women (20-45 years old) were studied, in four age matched groups: 39 controls, 18 obese without hirsutism, 11 non-obese hirsute and 14 obese hirsute women.. Blood samples were taken between days 5 and 7 of the menstrual cycle. Steroid hormone levels were measured by radioimmunoassay. Free testosterone levels were measured by equilibrium dialysis.. Compared to controls, mean free testosterone levels were increased (P less than 0.01) in obese, obese hirsute and hirsute patients, whereas mean DHEAS levels were increased in hirsute and obese hirsute (P less than 0.01), but not in obese, women. Mean androstanediol glucuronide levels were markedly increased in hirsute and obese hirsute patients (P less than 0.01), but not in obese women. Plasma androsterone glucuronide levels were increased in hirsute (P less than 0.01), in the normal range in obese hirsute, and decreased in obese women (P less than 0.01).. These results show that, despite the presence of higher free testosterone levels, neither 5 alpha-reductase activity (as suggested by normal androstanediol glucuronide levels) nor adrenal androgen precursor levels (DHEAS) are increased in obese women without hirsutism.

Topics: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase; Adult; Androstane-3,17-diol; Androsterone; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Hirsutism; Humans; Obesity; Testosterone

Assessment of an in vivo test for 5 alpha-reductase activity using serum markers, 5 alpha-androstane-3 alpha,17 beta-diol glucuronide and androsterone glucuronide, after the cutaneous application of androstenedione (A).. An A gel was applied for 6 days to the skin of normal women, male volunteers, and hirsute and nonhirsute patients with polycystic ovarian syndrome (PCOS). Blood samples were obtained at baseline and on day 6 of the A gel application. Blood samples were assayed for A, 5 alpha-androstane-3 alpha,17 beta-diol glucuronide, and androsterone glucuronide. In three hirsute women, the protocol was followed before and after receiving an oral contraceptive (OC) and spironolactone 200 mg/d for 3 months.. The study was performed in the outpatient clinic of the Division of Reproductive Endocrinology and Infertility, Women's Hospital of the Los Angeles County and University of Southern California Medical Center in Los Angeles, California.. A total of eight nonhirsute patients with PCOS, seven hirsute patients with PCOS, and six male volunteers were enrolled in the study. Five normal women served as a control group.. Serum A increased after 6 days by a similar magnitude in all groups. Serum androsterone glucuronide showed a significant increase from baseline only in the hirsute group (P < 0.03), whereas the increase in 5 alpha-androstane-3 alpha,17 beta-diol glucuronide was not statistically significant.. The ratio of the increases in serum androsterone glucuronide over serum A was significantly higher in the hirsute group (P < 0.02). In the three hirsute patients who were placed on an OC and spironolactone, serum 5 alpha-androstane-3 alpha,17 beta-diol glucuronide and androsterone glucuronide decreased after 3 months and did not increase with application of the gel for another 6 days.. The cutaneous application of A provides a useful assessment of in vivo 5 alpha-reductase activity. However, because we found that A absorption varied considerably (30% to 62%), we suggest that this in vivo test may not provide more information than baseline determinations of 5 alpha-androstane-3 alpha,17 beta-diol glucuronide and androsterone glucuronide. It may, however, be useful as a parameter for assessing the effectiveness of various treatment regimens for hirsutism.

Topics: Administration, Cutaneous; Adult; Androstane-3,17-diol; Androstenedione; Androsterone; Cholestenone 5 alpha-Reductase; Female; Gels; Hirsutism; Humans; Male; Oxidoreductases; Polycystic Ovary Syndrome

To explore the clinical usefulness of the antiandrogen flutamide in the treatment modality for hirsutism in women.. Nine women with hirsutism were assessed before and then monthly for 3 months on a regimen of flutamide 250 mg three times a day as the sole therapeutic agent. Blood samples were taken at each assessment time for a battery of androgenic parameters.. Patients were followed in the Out-Patient Department of the Hospital das Clinicas, Sao Paulo, Brazil. Hormonal assays were performed in the Hormone Laboratories of Hospital das Clinicas and the Endocrine Research Laboratory at Newark Beth Israel Medical Center, Newark, New Jersey.. Nine women with moderate hirsutism were treated with flutamide. Six women were previously diagnosed as having idiopathic hirsutism, and three women were diagnosed as having polycystic ovary syndrome.. All women were treated with flutamide 250 mg three times a day for 3 months.. Improvement of hirsutism was assessed using the Ferriman-Gallwey hair density index. Side effects of drug therapy (deterioration of menses and dry skin) were explored. Androgen parameters included testosterone (T), sex hormone-binding globulin, bound, nonbound, and free T, androstanediol glucuronide, and others.. After 3 months of flutamide alone, Ferriman-Gallwey scores improved in seven of nine women with mean scores decreasing from 28.1 +/- 0.6 to 24.5 +/- 0.6. None of the androgenic parameters changed during this period of time. Follicle-stimulating hormone and luteinizing hormone response to gonadotropin-releasing hormone was unchanged after flutamide.. Flutamide favorably influenced hirsutism in women, with differences noted after only 3 months of therapy. More prolonged and detailed studies of this drug as the sole therapeutic agent for treatment of hirsutism seems warranted.

Topics: Adult; Analysis of Variance; Androstane-3,17-diol; Androstenedione; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Estradiol; Female; Flutamide; Hirsutism; Humans; Polycystic Ovary Syndrome; Sex Hormone-Binding Globulin; Testosterone; Treatment Outcome

We investigated peripheral androgen metabolic activity in 54 hirsute females (HF) by evaluating the serum 3 alpha-androstanediol glucuronide (3AG) concentration, hirsutism score (HS), and etiology of hirsutism. Based on basal and ACTH-stimulated steroid profiles (1 h post-Cortrosyn, 0.25 mg, i.v. bolus), the causes of hirsutism were determined to be increased adrenal androgen production (greater than 2 SD above normal mean), increased ovarian testosterone (T) production (greater than 2 SD above normal mean basal T of ovarian source only), or idiopathic cause (normal steroid profile). Serum 3AG levels in each group of HF were significantly higher (P less than 0.01-0.001) than those in normal females [normal: 2.9 +/- 0.94 nmol/L (n = 28); HF: increased adrenal androgen production of undefined cause, 7.7 +/- 7.5 nmol/L (n = 14); 21-hydroxylase deficiency, 7.6 +/- 7.4 nmol/L (n = 5); increased ovarian T production 5.5 +/- 3.5 nmol/L (n = 18); idiopathic cause, 5.8 +/- 4.8 nmol/L (n = 17)]. However, normal 3AG levels (less than 5.2 nmol/L) were present in 50-67% of HF in each group. Collectively, 3AG levels in HF correlated significantly (P less than 0.01) with dehydroepiandrosterone (DHEA; r = 0.41) and DHEA sulfate (DS; r = 0.44), while the correlation with androstenedione (r = 0.15) or T (r = 0.19) was not significant. Serum 3AG and adrenal androgen levels decreased in all subjects after dexamethasone treatment (0.5-1 mg at hour of sleep; 2 mg/day for 3-5 days). The correlation between 3AG and HS was significant (r = 0.6-0.74; P less than 0.01-0.001) only in HF with increased adrenal androgen secretion and idiopathic cause, and was not significant (r = 0.42) in HF with increased ovarian T secretion. There was no significant correlation between androgen levels and HS. We conclude that the serum 3AG level was not consistently elevated in HF and did not differ significantly between the various causes. Significant correlations between 3AG and DHEA/DS levels, and the simultaneous decrease in 3AG and adrenal androgens after dexamethasone administration in HF suggest that adrenal androgens contribute significantly to 3AG production. The significant correlation between 3AG and HS in HF with increased adrenal androgen secretion and idiopathic cause indirectly suggests an adrenal androgen contribution to both 3AG production and hirsutism in these HF. The insignificant correlation between 3AG and HS in HF with increased ovarian T secretion may result from a confoundin

Topics: Adolescent; Adrenal Glands; Adult; Androgens; Androstane-3,17-diol; Dehydroepiandrosterone; Dexamethasone; Female; Hirsutism; Humans; Male; Ovary; Reference Values; Testosterone

Measurement of serum 5 alpha-androstane-3 alpha, 17 beta-diol glucuronide (3 alpha-diolG) has been proposed as a useful biochemical marker of peripheral androgen metabolism. Is 3 alpha-diol G a useful biochemical marker of peripheral androgen metabolism and does it correlate with degree of facial hirsutism?. Our purpose was to assess possible correlation between serum 3 alpha-diol G and degree of facial hirsutism and to compare serum 3 alpha-diol G levels with levels of other commonly measured serum androgens.. Twenty-three consecutive women with facial hirsutism were studied, and serum concentrations of 3 alpha-diol G, testosterone (total, free, and biologically active portions), dehydroepiandrosterone sulfate, and androstenedione were measured.. There was no correlation between serum 3 alpha-diol G levels and degree of facial hirsutism. There was a correlation between levels of 3 alpha-diol G and dehydroepiandrosterone sulfate (p less than 0.01), biologically active testosterone (p = 0.01), free free testosterone (p less than 0.02), and androstenedione (p less than 0.05).. Serum 3 alpha-diol G concentrations have no correlation with degree of facial hirsutism and do not provide additional information over the commonly measured androgens.

Topics: Adolescent; Adult; Androgens; Androstane-3,17-diol; Biomarkers; Facial Dermatoses; Female; Hirsutism; Humans

To determine if among hyperandrogenic women acne may be differentiated from hirsutism by markers of peripheral androgen metabolism.. Prospective outpatient study of 36 hyperandrogenic women and controls divided into groups based on the presence or absence of significant hirsutism and the presence or absence of moderate to severe acne. Serum levels of adrenal and ovarian derived androgens were elevated but similar in all patient groups.. Measurement of serum androgens including metabolites of 5 alpha-reductase activity: 3 alpha-androstanediol glucuronide and sulfate and androsterone (A) glucuronide and sulfate.. 3 alpha-androstanediol glucuronide and sulfate were elevated in all groups (P less than 0.05) and could differentiate between hirsute and nonhirsute patients but were similar in patients with and without acne. Serum A glucuronide and sulfate were only significantly elevated in patients with acne (P less than 0.01) and were higher than levels in controls and hirsute patients without acne. Ratios of precursor androgens to A glucuronide and sulfate were significantly higher in patients with acne compared with patients without acne (P less than 0.05).. Altered peripheral metabolism in acne may favor the formation of A conjugates, which may help differentiate acne from hirsutism among hyperandrogenic women.

Topics: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase; Acne Vulgaris; Adolescent; Adult; Androgens; Androstane-3,17-diol; Androstenedione; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Diagnosis, Differential; Female; Hirsutism; Humans; Prospective Studies; Testosterone

Serum 5 alpha-androstane-3 alpha,17 beta-diolglucuronide (3 alpha-AdiolG) levels were measured and the degree of hirsutism was scored in female outpatients complaining of excessive hair growth before and during treatment with cyproterone acetate. In a group of 16 patients with idiopathic hirsutism and in a group of 9 patients with either polycystic ovary syndrome and hirsutism or 21-hydroxylase deficiency and hirsutism, the serum 3 alpha-AdiolG levels were significantly increased (p less than 0.01) as compared with the serum 3 alpha-AdiolG level in a control group of 13 apparently healthy women: 3 alpha-AdiolG levels, median (range), being 5.3 (2.3-7.8) nmol/l, 8.5 (4.1-10.4) nmol/l, and 2.9 (1.5-5.2) nmol/l, respectively. In contrast to a previous report, no correlation was found between the serum 3 alpha-AdiolG levels and the Quetelet Index (N = 18, R = 0.42, p greater than 0.05), indicating an apparent ineffectiveness of the excessive androgen turnover in fat tissue. The use of the anti-androgen drug cyproterone acetate alone or in combination with ethinylestradiol in reverse sequential therapy did lower the 3 alpha-AdiolG levels significantly (p less than 0.01) together with a significant decrease (p less than 0.01) in hirsutism score. From the results of this study we therefore conclude that 3 alpha-AdiolG can be used as a parameter for peripheral androgen action before and during treatment with anti-androgens.

Topics: Androgen Antagonists; Androgens; Androstane-3,17-diol; Cyproterone; Cyproterone Acetate; Female; Hirsutism; Humans; Polycystic Ovary Syndrome

We investigated whether plasma androstanediol glucuronide (ADG) levels reflect the increased androgenicity in women with idiopathic hirsutism (n = 24) or hirsutism associated with polycystic ovary syndrome (n = 10). We also evaluated whether ADG levels parallel the clinical evolution of the hirsutism during a combined treatment, with cyproteroneacetate (2 mg) and ethinylestradiol (35 micrograms), of women with moderate idiopathic hirsutism. Finally, we investigated if there is evidence for increased conversion of precursors to ADG in hirsutism, by comparing the ADG levels, measured by RIA, to ADG levels obtained by applying the conversion rates of precursors obtained in non-hirsute women. ADG levels were increased in less than half of the patients with mild hirsutism. The clinical cure of hirsutism, which was obtained by the treatment in majority of patients, was accompanied by a significant decrease of plasma ADG levels, but a similar decrease was also observed in the 5 patients who did not respond to treatment. The data show that, although there is evidence for increased conversion of precursors to plasma ADG in mildly hirsute women, the latter is not a reliable parameter of androgenicity. Our data suggest, moreover, that treatment with cyproterone acetate and ethinylestradiol decreases 5 alpha-reductase activity, as indicated by the more important decrease in ADG levels than in the precursors.

Topics: Adult; Androgen Antagonists; Androstane-3,17-diol; Biomarkers; Cyproterone; Cyproterone Acetate; Ethinyl Estradiol; Female; Hirsutism; Humans; Middle Aged; Polycystic Ovary Syndrome

Hirsutism in women is often explained on the basis of abnormal peripheral androgen metabolism. To determine whether serum markers of ovarian, adrenal, or peripheral androgen production may be helpful determinants in the treatment of hirsutism and to compare the efficacy of treatment with dexamethasone or spironolactone, 20 hyperandrogenic hirsute patients were treated for up to 2 years. Eleven women who were selected on the basis of sensitivity to dexamethasone were treated with a daily dose of 0.37 mg dexamethasone and had androgen levels suppressed into the normal range. Although significant (P less than .05), Ferriman-Gallwey scores decreased only by 20%: 14.2 +/- 0.5 to 11.4 +/- 0.6. Nine other women received spironolactone 100 mg/day for 1 year and did not have significant changes in serum androgens, but had a significant (P less than .01) 47% reduction in the Ferriman-Gallwey score (15.2 +/- 0.8 to 8 +/- 0.8). Thus, with either treatment, the reduction in Ferriman-Gallwey scores did not correlate with the change in androgen levels. The patients treated with dexamethasone for 1 year then received spironolactone 100 mg/day together with dexamethasone for an additional year. Serum androgen levels did not change further, but the Ferriman-Gallwey scores decreased significantly (P less than .01) from 11.4 +/- 0.6 to 3.74 +/- 0.7 (-61%). These data suggest that serum androgens are not helpful in assessing response to the treatment of hirsutism and that despite normal androgen levels, only modest clinical improvement may be expected with dexamethasone treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Androgen Antagonists; Androgens; Androstane-3,17-diol; Androstenedione; Androsterone; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Dexamethasone; Dihydrotestosterone; Drug Combinations; Female; Hirsutism; Humans; Spironolactone; Testosterone

Plasma androstanediol-glucuronide (ADG) is considered by many authors to be a highly reliable parameter of peripheral androgenicity. Recently, several authors have questioned the reliability of the ADG levels as a parameter of androgenicity. Our data obtained by continuous infusion experiments showed that in women the adrenal steroids, dehydroepiandrosterone sulfate, androstenedione and dehydroepiandrosterone are the major precursors of plasma ADG, accounting for almost the totality of circulating ADG. As expected, in view of its precursors, ADG levels decrease significantly with age. Dexamethasone causes a significant decrease of these levels, whereas in women with Addison's disease the levels are only 20% of normal levels; ovariectomy hardly influences ADG levels. Our data show that in women with moderate hirsutism, plasma ADG levels are no more often increased than the other androgens. In virilizing syndromes ADG levels are higher than expected from precursor levels, suggesting an increased 5 alpha-reductase activity. In hyperthyroidism as well as in euthyroid women with isolated suppressed thyroid stimulating hormone, ADG levels are increased without any sign of virilism. In men, ADG levels have testosterone as a major precursor, but the adrenals contribute to +/- 30% of ADG levels. After transdermal dihydrotestosterone gel, free androstanediol levels increased by a factor of 40, but ADG levels were only increased by a factor of 4, suggesting that the skin is not very effective in conjugating androstanediol. It is concluded that ADG levels in women reflect essentially adrenal precursor levels as well as 5 alpha-reductase activity in peripheral tissues inclusive of the liver.

Topics: Adolescent; Adult; Androstane-3,17-diol; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Dihydrotestosterone; Female; Hirsutism; Humans; Middle Aged; Virilism

Topics: Androstane-3,17-diol; Hirsutism; Humans; Male; Testosterone

We described a chemiluminescent immunoassay (CIA) for 5 alpha-androstane-3 alpha, 17 beta-diol-glucuronide (3 alpha-diol-G) in human diluted urine. This method allowed the direct measurement in 1 microliter of urine avoiding the hydrolysis and extraction steps for sample pretreatment commonly used in routine methods. The hapten 3 alpha-diol-G was synthesized by a Koenigs-Knorr reaction. The immunogenic complex, 3 alpha-diol-G conjugated to bovine serum albumin (BSA), was employed to induce the formation of specific antibodies in New Zealand rabbits. In addition, the required chemiluminescent (CL) tracer was prepared. The characteristics of the antibody was determined as regard to specificity and sensitivity and the precision of the assay methods established. In 22 hirsute women affected by polycystic ovarian syndrome we found 3 alpha-diol-G values significantly (p less than 0.01) higher (146.28 +/- 73.77 micrograms/g of creatinine; mean +/- SD) than those observed in normal women (72.1 +/- 32.58 micrograms/g of creatinine; mean +/- SD).

Topics: Adult; Androstane-3,17-diol; Androstanols; Female; Hirsutism; Humans; Immunoassay; Luminescent Measurements; Reference Standards

There is currently much interest in measurements of 5 alpha-androstane-3 alpha, 17 beta-diol glucuronide (AdiolG) as a marker of peripheral androgen metabolism. We have therefore developed an assay to measure serum AdiolG levels and report that mean concentrations in hirsute (2.9 +/- 1.9 nmol/l, mean +/- SD, n = 15) and non-hirsute (1.9 +/- 0.6 nmol/l, n = 7) women with polycystic ovaries do not differ significantly from concentrations in normal women (2.2 +/- 0.8 nmol/l, n = 20). However, a correlation was found between serum AdiolG levels and Body Mass Index (r = 0.48, P less than 0.05) for women with polycystic ovaries, suggesting that weight may be an important factor in determining concentrations of this steroid conjugate. Serum AdiolG levels were significantly reduced in hypothyroid women (0.6 +/- 0.4 nmol/l, n = 5) and women receiving oral contraceptive therapy (0.6 +/- 0.4 nmol/l, n = 28) but increased in hyperthyroid women (4.0 +/- 0.6 nmol/l, n = 5). The results from this study do not support the hypothesis that serum AdiolG levels provide a marker of peripheral androgen metabolism in hirsute women and show that it is essential to exclude from such investigations any women with thyroid abnormalities or receiving oral contraceptive therapy.

Topics: Adult; Androstane-3,17-diol; Androstanols; Body Height; Body Weight; Contraceptives, Oral; Dihydrotestosterone; Female; Hirsutism; Humans; Polycystic Ovary Syndrome; Thyroid Diseases

Serum androstanediol glucuronide (3 alpha-diol G), a metabolite of the active androgens dihydrotestosterone and androstanediol, was elevated in 28 consecutive women with idiopathic hirsutism (IH). The mean 3 alpha-diol G level in the women with IH was 487 +/- 192 (+/- SD) ng/dL compared to 119 +/- 37 ng/dL in normal women (n = 50), and only 1 patient had a value overlapping with the normal range. Since 3 alpha-diol G appears to be formed entirely in target organs and has a long serum half-life, we studied its clinical usefulness by following women with IH during treatment. In 15 of 17 women with IH treated for 1-4 yr with glucocorticoids, contraceptives, or spironolactone, serum 3 alpha-diol G levels changed concordantly with clinical responses, in contrast to the poor concordance of serum testosterone (5 of 17), free testosterone (7 of 17), and androstenedione (7 of 17). Specifically, in IH patients treated with spironolactone, serum testosterone, free testosterone, and androstenedione levels changed little, yet clinical improvement frequently occurred, and this improvement was reflected by concomitantly lowered 3 alpha-diol G levels. Further, in 4 IH patients, discontinuation of effective therapy resulted in prompt increases in serum 3 alpha-diol G as harbingers of worsening hair growth. We, thus, conclude that serum 3 alpha-diol G measurements are clinically useful in evaluating hirsute women and correlate with the clinical responses to therapy.

Topics: Adolescent; Adult; Androstane-3,17-diol; Androstanols; Contraceptives, Oral, Combined; Contraceptives, Oral, Synthetic; Drug Combinations; Female; Hirsutism; Humans; Mestranol; Monitoring, Physiologic; Norethindrone; Prednisone; Spironolactone; Time Factors

Although hyperprolactinemia may be associated with hyperandrogenism, if hirsutism develops, it is usually a mild form. This study was designed to investigate whether prolactin (PRL) modulates 5 alpha-reductase activity (5 alpha-RA), because 5 alpha-RA is known to be a major factor influencing the manifestation of androgenicity. Compared with normal women, euprolactinemic hirsute and both hyperprolactinemic hirsute and nonhirsute women had elevated levels of unbound testosterone (uT). Serum 3 alpha-androstanediol glucuronide (3 alpha-diol-G) was elevated only in patients who were hirsute, and serum 3 alpha-diol-G/uT ratios were elevated in euprolactinemic hirsute patients and normal in hyperprolactinemic hirsute patients. Genital skin 5 alpha-RA in vitro was elevated only in euprolactinemic hirsute women. The previously recognized positive correlation between 5 alpha-RA and the severity of hirsutism was dissociated with hyperprolactinemia. Human PRL incubated in vitro with normal genital skin also inhibited 5 alpha-RA. These data suggest that PRL modulates 5 alpha-RA and peripheral androgen metabolism and that other factors may also be involved in the evolution of hirsutism in hyperprolactinemia.

Topics: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase; Adult; Androgens; Androstane-3,17-diol; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Dihydrotestosterone; Female; Genitalia, Female; Hirsutism; Humans; Hyperprolactinemia; In Vitro Techniques; Middle Aged; Prolactin; Skin; Testosterone

The role of glucocorticoid therapy in regulating plasma 3 alpha-androstanediol glucuronide (3 alpha-diol G) content, a marker of androgen action, in hirsute women was unclear. A pulse injection of adrenocorticotropic hormone (0.5 U) following 1 mg of dexamethasone (DEX) at midnight significantly increased the plasma level of cortisol (P less than 0.01), 17-hydroxyprogesterone (17-OHP, P less than 0.01) in 17 hirsute women, but it had an insignificant effect on delta 4-androstenedione (delta 4A), testosterone, dehydroepiandrosterone sulfate (DHEA-S), and 3 alpha-diol G. Human chorionic gonadotropin administered for 3 days produced a significant (P less than 0.01) increase only in 17-OHP. DEX administered as a single dose in the late evening failed to affect the plasma levels of these four androgens when measured at 8:00 A.M. In contrast, when the glucocorticoid was given each evening for over 2 months, plasma delta 4A, DHEA-S, and 3 alpha-diol G were suppressed (P less than 0.001) substantially, as compared with baseline values in 12 hirsute women, 7 with polycystic ovary disease and 5 with idiopathic hirsutism. These observations indicate that chronic glucocorticoid therapy suppresses androgen action in hirsute women.

Topics: 17-alpha-Hydroxyprogesterone; Adrenocorticotropic Hormone; Androstane-3,17-diol; Androstanols; Chorionic Gonadotropin; Dehydroepiandrosterone; Dexamethasone; Hirsutism; Hydrocortisone; Hydroxyprogesterones; Testosterone

Serum and urinary measurements of 3 alpha,17 beta-androstanediol glucuronide (3 alpha-diol G) reflect peripheral androgen action and have been useful clinically. This study was designed to compare these levels in hirsute women, normal premenopausal and postmenopausal women, and in men and to correlate each measurement with skin 5 alpha-reductase activity (5 alpha-RA), an excellent correlate of androgenicity. Although serum 3 alpha-diol G values were similar in premenopausal and postmenopausal women, values were higher in hirsute women and in men. This pattern was similar for urinary 3 alpha-diol G but with greater overlap in values between hirsute and nonhirsute women and men. Serum 3 alpha-diol G showed a highly significant correlation with levels of genital 5 alpha-RA (r = 0.839, P less than 0.001), whereas urinary 3 alpha-diol G did not correlate. Serum and urinary 3 alpha-diol G also did not correlate with one another (r = 0.03). These data suggest that while both serum and urinary 3 alpha-diol G may be useful clinically, serum 3 alpha-diol G appears to correlate better with androgenicity and 5 alpha-RA. It is suggested further that the sources of serum and urinary 3 alpha-diol G may be somewhat different.

Topics: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase; Adult; Aged; Androstane-3,17-diol; Androstanols; Female; Hirsutism; Humans; Male; Menopause; Middle Aged; Skin

We studied the kinetics and metabolism of tritiated 5 alpha-androstane-3 alpha-17 beta-diol glucuronide (3 alpha diolG) in normal and hirsute women. We found no difference in the MCR of 3 alpha diolG between normal and hirsute women [130 +/- 39 (+/- SD) vs. 157 +/- 81; P = NS]. The blood production rate was markedly increased in hirsute women (187 +/- 50 vs. 604 +/- 355 micrograms/day; P less than 0.001) and correlated well with the plasma 3 alpha diolG level (r = 0.96). In women, the conversion ratio of 3 alpha diolG to unconjugated 3 alpha diol or dihydrotestosterone was less than 1%, while the conversion ratio to dihydrotestosterone glucuronide was about 6%. We conclude that the elevated plasma levels of 3 alpha diolG characteristic of hirsutism reflect increased production of this androgen metabolite.

Topics: Adult; Androstane-3,17-diol; Androstanols; Female; Hirsutism; Humans; Kinetics; Metabolic Clearance Rate; Polycystic Ovary Syndrome; Reference Values; Tritium

To confirm that plasma delta 4 androstenedione (delta 4) is the main precursor for 5 alpha-androstane-3 alpha, 17 beta-diol glucuronide (Adiol G) in patients with idiopathic hirsutism (IH), delta 4 was cutaneously applied to five normal women and five women with IH. Several parameters of androgen metabolism were assayed basally and throughout the studies. Those included plasma delta 4, testosterone, and dihydrotestosterone as well as urinary Adiol G and testosterone glucuronide excretion. Under basal conditions plasma testosterone, delta 4, and dihydrotestosterone did not differ significantly between the two groups of subjects. Urinary Adiol G excretion was significantly higher (P less than 0.01) in IH patients [123 +/- 36 (SE) micrograms/24 h] than in the normal women group (45 +/- 20 micrograms/24 h). After percutaneous administration of delta 4, plasma delta 4 increased in both groups by nearly 600% and there was a 300% increase in Adiol G excretion in IH patients (336 +/- 57 micrograms/24 h), whereas only a 50% increase occurred in normal women (65 +/- 17 micrograms/24 h). We postulate that plasma delta 4 may be the main precursor accounting for the increased production of urinary Adiol G in women with IH, in whom hirsutism may be due to a high 5 alpha-reductase activity. Indeed, 5 alpha-reductase as measured in vitro in pubic skin was significantly higher in hirsute patients (224 +/- 66 fmol/mg skin X h) than in normal women (45 +/- 15 fmol/mg skin X h).

Topics: Adolescent; Adult; Androstane-3,17-diol; Androstanols; Androstenedione; Cholestenone 5 alpha-Reductase; Dihydrotestosterone; Female; Hirsutism; Humans; In Vitro Techniques; Oxidoreductases; Skin; Testosterone

In vitro, genital skin 5 alpha-reductase activity (5 alpha-RA) was measured in ten hirsute women with normal androgen levels (idiopathic hirsutism [IH]) and in ten hirsute women with elevated androgen levels (polycystic ovary syndrome [PCO]) in order to determine the influence of secreted androgens on 5 alpha-RA. In vitro 5 alpha-RA was assessed by incubations of skin with 14C-testosterone (T) for 2 hours, after which steroids were separated and the radioactivity of dihydrotestosterone (DHT) and 5 alpha-androstane 3 alpha-17 beta-estradiol (3 alpha-diol) in specific eluates were determined. All androgens were normal in IH with the exception of higher levels of 3 alpha-diol glucuronide which were similar to the levels of PCO. The conversion ratio (CR) of T to DHT in IH (17.18% +/- 4.6%) and PCO (17.86% +/- 5.2%) were similar, yet significantly greater than the CR of control subjects (4.48% +/- 0.36% P less than 0.01). The CR of T to 3 alpha-diol in IH (8.00% +/- 1.38%) and PCO (10.36% +/- 1.0%) were similar, yet higher than in control subjects (2.96% +/- 0.32%; P less than 0.05). Serum androgens showed no correlation with 5 alpha-RA, while the CR of T to DHT showed a significant positive correlation with the Ferriman and Gallwey score (r = 0.61; P less than 0.01). The increased 5 alpha-RA in IH appears to be independent of serum androgen levels and is, therefore, an inherent abnormality. The term "idiopathic" is a misnomer, because hirsutism in these patients may be explained on the basis of increased skin 5 alpha-RA.

Topics: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase; Adult; Androstane-3,17-diol; Androstenedione; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Dihydrotestosterone; Female; Genitalia, Female; Hirsutism; Humans; Luteinizing Hormone; Oxidoreductases; Polycystic Ovary Syndrome; Skin; Testosterone

Hirsutism can occur in the presence of normal or near normal levels of serum testosterone, unbound testosterone (uT), dehydroepiandrostene sulfate, androstenedione, and dihydrotestosterone. However, we have found that serum androstanediol glucuronide (3 alpha-diol G) is markedly increased in idiopathic hirsutism and it serves as an excellent marker of peripheral androgen metabolism and action. In the present work, we studied 12 hirsute (H) and 12 nonhirsute (NH) patients with polycystic ovary syndrome (PCO) and 13 age and weight matched controls in order to determine if differences in sex steroid levels or peripheral tissue androgen events were associated with hirsutism. Serum unbound estradiol levels and LH-FSH ratios were similar in both groups of women with PCO, and both were significantly higher than levels in controls (P less than 0.05). Whereas serum testosterone, uT, and androstenedione were elevated in both H-PCO and NH-PCO patients compared to controls, the levels in these two groups were similar. Serum dehydroepiandrostene sulfate was higher in PCO patients compared to controls, but H-PCO patients had slightly higher levels than NH-PCO patients. Serum delta 5-androstenediol was also slightly higher in H-PCO compared to NH-PCO patients. Dihydrotestosterone was normal and unconjugated; 3 alpha-diol was higher than normal in both groups of patients with PCO, although H-PCO patients had higher levels than NH-PCO patients. Compared to these relatively minor changes between the PCO patient groups, serum 3 alpha-diol G was markedly elevated in H-PCO patients (approximately 10-fold), yet normal in NH-PCO patients (P less than 0.01). The ratios of serum 3 alpha-diol G-uT were similar in NH-PCO patients and controls, but were elevated in H-PCO patients (P less than 0.01). These data indicate that: 1) women with PCO have increased circulating androgen levels regardless of the presence or absence of hirsutism; and 2) the presence of hirsutism is not only a function of circulating androgen levels, but may also be determined by events in peripheral tissues.

Topics: Adolescent; Adult; Androgens; Androstane-3,17-diol; Androstanols; Androstenediol; Androstenedione; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Hirsutism; Humans; Polycystic Ovary Syndrome; Testosterone

Biologically active androgens and peripheral androgen metabolites in plasma were measured in 25 women with idiopathic hirsutism (IH). Plasma testosterone was not significantly elevated. Free testosterone however was increased although the elevation was not impressive (10.9 +/- 6.6 SD vs. 3.3 +/- 1.5 ng/dl) and one-fourth of the cases had normal unbound testosterone. Dihydrotestosterone (DHT) values were elevated (23.5 +/- 14 vs. 12.5 +/- 3.59) but again over half of the values were within the normal range. In our series of mild to moderate cases, 3 alpha-diol was not at all discriminatory. However, plasma 3 alpha-diol glucuronide was markedly increased (604 +/- 376 vs. 40 +/- 10 ng/dl), and elevated in all but one mild case. Previous studies document that DHT is the important androgen in skin and formation of DHT and 3 alpha-diol is markedly increased in vitro in IH. Since 3 alpha-diol glucuronide is derived largely from extrasplanchnic events, beta-glucuronidase is present in skin, and androgen stimulates formation of the enzyme in extrasplanchnic tissue, we conclude that 3 alpha-diol glucuronide is a marker of peripheral androgen action and markedly elevated in IH.

Topics: Androstane-3,17-diol; Androstanols; Dihydrotestosterone; Female; Hirsutism; Humans; Skin; Testosterone