androstane-3-17-diol-glucuronide and Hyperandrogenism

Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age, is characterized by hyperandrogenism, oligo/amenorrhea, and polycystic ovaries. We aimed to determine whether low-frequency electro-acupuncture (EA) would decrease hyperandrogenism and improve oligo/amenorrhea more effectively than physical exercise or no intervention. We randomized 84 women with PCOS, aged 18-37 yr, to 16 wk of low-frequency EA, physical exercise, or no intervention. The primary outcome measure changes in the concentration of total testosterone (T) at week 16 determined by gas and liquid chromatography-mass spectrometry was analyzed by intention to treat. Secondary outcome measures were changes in menstrual frequency; concentrations of androgens, estrogens, androgen precursors, and glucuronidated androgen metabolites; and acne and hirsutism. Outcomes were assessed at baseline, after 16 wk of intervention, and after a 16-wk follow-up. After 16 wk of intervention, circulating T decreased by -25%, androsterone glucuronide by -30%, and androstane-3α,17β-diol-3-glucuronide by -28% in the EA group (P = 0.038, 0.030, and 0.047, respectively vs. exercise); menstrual frequency increased to 0.69/month from 0.28 at baseline in the EA group (P = 0.018 vs. exercise). After the 16-wk follow-up, the acne score decreased by -32% in the EA group (P = 0.006 vs. exercise). Both EA and exercise improved menstrual frequency and decreased the levels of several sex steroids at week 16 and at the 16-wk follow-up compared with no intervention. Low-frequency EA and physical exercise improved hyperandrogenism and menstrual frequency more effectively than no intervention in women with PCOS. Low-frequency EA was superior to physical exercise and may be useful for treating hyperandrogenism and oligo/amenorrhea.

Topics: Acneiform Eruptions; Adolescent; Adult; Amenorrhea; Androstane-3,17-diol; Androsterone; Combined Modality Therapy; Electroacupuncture; Exercise; Female; Humans; Hyperandrogenism; Menstrual Cycle; Motor Activity; Oligomenorrhea; Polycystic Ovary Syndrome; Severity of Illness Index; Testosterone; Time Factors; Young Adult

Premature pubarche (PP) appears to be a risk factor for the subsequent development of polycystic ovary syndrome (PCOS) during or after puberty. The clinical manifestations due to hyperandrogenism are influenced by androgen production, androgen metabolism, and androgen receptor activity. Glucuronidation by the UDP-glucuronyltransferase 2B (UGT2B) family of enzymes is one mechanism through which androgens are inactivated. Two variants differing by the amino acid at codon 85 have been described for UGT2B15, a member of this family. Both variants show similar substrate specificities. However, for the substrates alpha-androstanediol (alpha-diol) and dihydrotestosterone (DHT), the D85 variant has a lower Vmax than the Y85 variant. We compared the frequencies of these variants in 69 patients with PP, 46 adolescent girls with hyperandrogenism (HA), and 88 healthy controls to determine whether the frequency of the D85 variant was increased among patients with hyperandrogenism. Allele frequencies were comparable in children with PP, adolescent girls with HA, and healthy control subjects. Although D85 and Y85 appear to be common variants, we cannot exclude the possibility that the UGT2B15 gene represents a minor modifying locus.

Topics: Adolescent; Androstane-3,17-diol; Androstenedione; Child; Dihydrotestosterone; Female; Gene Frequency; Genotype; Glucuronosyltransferase; Heterozygote; Homozygote; Humans; Hyperandrogenism; Phenotype; Polycystic Ovary Syndrome; Puberty, Precocious; Sex Hormone-Binding Globulin; Testosterone

The roles of androgen hypersecretion, in situ enzyme activity, and androgen receptors in androgenetic alopecia in women are still a matter of debate. We studied 187 women with alopecia, which we graded I, II, or III, according to Ludwig's classification, and 21 healthy control women. All participants were subjected to full basal and 1 h post-beta-1-24 corticotropin stimulation endocrine profiles. Abnormal hormone profiles were observed in 67% of the patients with alopecia alone (group A, n = 110) and in 84% of the patients with alopecia plus other symptoms of hyperandrogenism including acne, hirsutism, and menstrual cycle disturbances (group B, n = 77). Mean serum 5alpha-androstane-3alpha,17beta-diol glucuronide (3alpha-AdiolG) levels in all three patient groups (6.50+/-4.10, 8.90+/-5.80, and 14.70+/-8.90 nmol/l, respectively) correlated with the grade of alopecia (I-III) and were significantly higher than in the control group (4.80+/-2.05 nmol/l, P < 0.005). Mean serum sex hormone-binding globulin (SHBG) levels were inversely correlated with the grade of alopecia (I-III) and were significantly lower in all three patient groups (50.55+/-23.50, 40.00+/-17.65, and 38.80+/-14.10 nmol/l, respectively) than in the control group (61.15+/-17.65 nmol/l, P < 0.05). Mean serum levels of delta4-androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and 3alpha-AdiolG were higher in group B than in group A, and higher in group A than in the control group. The significant correlations found between adrenal secretion - either positive (with 3alpha-AdiolG levels and the body mass index) or negative (with SHBG levels) - might reflect the important contribution of secretory and metabolic components in the development of alopecia, the severity of which has been shown to be very closely related to observed levels of two of these parameters (3alpha-AdiolG and SHBG).

Topics: Adolescent; Adult; Age of Onset; Alopecia; Androgens; Androstane-3,17-diol; Case-Control Studies; Female; Humans; Hyperandrogenism; Middle Aged; Severity of Illness Index; Sex Hormone-Binding Globulin

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

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