Serum androsterone conjugates differentiate between acne and hirsutism in hyperandrogenic women.

OBJECTIVE: To determine if among hyperandrogenic women acne may be differentiated from hirsutism by markers of peripheral androgen metabolism. DESIGN: 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. INTERVENTIONS: Measurement of serum androgens including metabolites of 5 alpha-reductase activity: 3 alpha-androstanediol glucuronide and sulfate and androsterone (A) glucuronide and sulfate. RESULTS: 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). CONCLUSIONS: Altered peripheral metabolism in acne may favor the formation of A conjugates, which may help differentiate acne from hirsutism among hyperandrogenic women.     

Treatment of hirsutism and acne in women with two combinations of cyproterone acetate and ethinylestradiol.

175 women of reproductive age, with hirsutism of differing degrees and different pathogenetic causes (ovarian, adrenal, iatrogenic) or idiopathic, and acne were treated with two different combinations of Cyprotrone acetate and ethinyl estradiol (SH 8.1041 and SH B209AB). 90 patients were given SH 8.1041 and 10 were given SH B209AB. 75 received both preparations. The total number of treatment cycles was 1534. Clinical, hormonal and biochemical assessments were made before, during and after treatment. The degrees of hirsutism and acne, and of seborrhea and hair loss when present, were scored by means of a modified version of the Ferriman and Gallway criteria. SH 8.1041 brought about a significant improvement in the majority of the patients. SH B209AB was generally used as maintenance therapy for hirsutism and severe acne. It was the initial treatment of choice in patients with milder acne. Reduction of hirsutism was usually apparent after the fourth cycle of therapy and acne regressed after the first month. Both combinations were well-tolerated biochemically. In a few patients on SH 8.1042, slight and transient increases in BSP, SGOT, SGPT and bilirubin were observed, but cessation of treatment was not necessary. Some patients on SH 8.1041 complained of transient frigidity, mild depression, breast discomfort and nausea.     

Cyproterone acetate - ethinylestradiol treatment of hirsutism, acne, seborrhea and alopecia]

Twenty-five female patients, aged 14 to 49, and suffering from syptoms of virilization (hirsutism, acne, seborrhea and alopecia) were treated with an estrogen-progestogen combinantion, i.e. cyproterone acetate and ethinylestradiol, having antiandrogenic and antiovulatory action. Patients were submitted to monitoring by means of a series of laboratory tests in order to detect any toxic or hormonal effects that might occur. In most cases symptoms of virilization were significantly reduced, while untoward side effects were not noted.     

Androgen receptor gene polymorphism and polycystic ovary syndrome

BackgroundPolycystic ovary syndrome (PCOS) is characterized by ovulatory dysfunction and hyperandrogenism. Its etiopathology is not well understood but genetic factors seem to have a role. Polymorphism of the androgen receptor (AR) gene has been associated with different androgen pattern diseases.ObjectiveTo review the association between AR gene polymorphism and PCOS.Search strategyA systematic review was performed via PUBMED, EMBASE, and LILACS (up to May 31, 2011).Selection criteriaStudies assessing the presence of the (CAG)_n polymorphism of the AR gene in at least 2 comparison groups (PCOS and control). Studies that did not contain adequate information were excluded.Data collection and analysisStudy characteristics and results were analyzed. Meta-analysis could not be performed because only 2 articles provided odds ratios.Main resultsTen studies met the inclusion criteria. Three studies reported a correlation between the polymorphism and PCOS; 2 studies linked the disorder to shorter repeats, whereas the other associated it with longer repeats.ConclusionPolymorphism of the AR gene seems to be a promising biomarker for PCOS because shorter repeats may be linked to the disorder. However, further studies are needed to understand the association fully.     

Androgen receptor gene polymorphism and prostate cancer in Taiwan.

BACKGROUND AND PURPOSE: The length of polymorphic CAG trinucleotide repeats in the polyglutamine region of the androgen receptor (AR) gene has been suggested to be inversely correlated with the transactivation function of the AR. An increase in androgen activity may be associated with prostate cancer, and ethnic variations in CAG repeat length may contribute to varying prostate cancer risks in different populations. This case-control study investigated the potential role of AR polymorphism in prostate cancer risk in Taiwanese. METHODS: Sixty six pathologically-confirmed prostate cancer patients and 104 controls were studied. CAG repeat polymorphism was genotyped by a polymerase chain reaction (PCR)-based direct sequencing method. Logistic regression was used to determine the relative risk of AR gene CAG number on prostate cancer risk. The associations of AR-CAG polymorphism with disease stage, pathologic grade, and age at diagnosis were assessed. AR-CAG repeat number was first treated as a continuous variable, then was divided into short and long groups (n < 23 vs n > or = 23) for categorical analysis. The extreme groups of AR-CAG distribution were also analyzed for these associations (n < or = 20 vs n > or = 26 and n = 21-25 vs n > or = 26). RESULTS: The mean number of CAG repeats in patients and controls was similar: 23.2 +/- 3.0 (range, 15 to 31) and 22.9 +/- 3.1 (range, 15 to 31), respectively. No association was found between AR-CAG repeat polymorphism and disease stage (p = 0.30), histological grade (p = 0.49), or age at diagnosis (p = 0.51). After adjusting for other covariates (age, body mass index, education level, smoking, and alcohol status), the number of AR-CAG repeats was not significantly associated with prostate cancer risk [odds ratio (OR) = 0.97, 95% confidence interval (95% CI) = 0.72 to 1.31; p = 0.84]. In categorical analysis, men with short CAG repeats (n < 23) did not have increased risk for prostate cancer (OR = 0.45, 95% CI = 0.29 to 1.05) compared to those with long CAG repeats (n > or = 23). Non-significant differences in prostate cancer risk were also found when comparing the extreme short group (n < or = 20) and the intermediate group (n = 21-25) to the extreme long group (n > or = 26) [n < or = 20 vs n > or = 26: OR = 1.00, 95% CI = 0.34 to 3.00; n = 21-25 vs n > or = 26: OR = 0.82, 95% CI = 0.37 to 1.81]. CONCLUSIONS: The results of this study do not support an important effect of AR-CAG repeat polymorphism on prostate cancer risk. A large-scale study is needed to clarify genetic components of prostate cancer risk in the Taiwanese population.     

Androgen receptor gene CAG repeat length in women with metabolic syndrome

Objective. The length of the androgen receptor gene CAG repeat [AR (CAG)_n] modulates the activity of the androgen receptor (AR), and this polymorphism has been shown to modulate body fat mass and serum concentrations of insulin in men. We hypothesized that shorter AR (CAG)_n is associated with metabolic syndrome (MBS) or its components in women.

Design, patients and measurements. In a cross-sectional controlled study we studied 52 Finnish women aged 34–55 years with MBS and 69 age-matched controls. All participants were recruited from a sample of women drawn from the Finnish population register. We compared the mean AR (CAG)_n in the two groups. Furthermore, we correlated the AR (CAG)_n with serum testosterone, androstenedione, dehydroepiandrosterone sulfate and several parameters of glucose and lipid metabolism in each group and in all 121 women.

Results. There was no difference in the biallelic mean AR (CAG)_n between the MBS and the control group (21.6±0.2 vs. 21.8±0.2, not significant). The AR (CAG)_n did not correlate significantly with any of the clinical or biochemical parameters of glucose or fat metabolism. However, it correlated negatively with serum testosterone (?0.195, p = 0.04) and androstenedione concentrations (?0.205, p = 0.03) in all studied women.

Conclusions. The AR (CAG)_n is not a major determinant of MBS in women but it contributes to ovarian androgen production.     

Efficacy of combined ethinyloestradiol (0.035 mg) and cyproterone acetate (2 mg) in acne and hirsutism in women with polycystic ovary syndrome.

The effects of an oral contraceptive containing ethinyloestradiol and cyproterone acetate on acne and hirsutism were studied in 82 women with polycystic ovary syndrome. The contraceptive was administered for 48 consecutive cycles. Hormone and ultrasound evaluations were carried out at baseline and after 48 treatment cycles. Acne and hirsutism were evaluated after 18, 24, 36 and 48 treatment cycles. Acne resolved in all patients within 24 treatment cycles. Mild and moderate hirsutism resolved within 48 treatment cycles. Severe hirsutism persisted although it changed to mild or moderate in most of the affected women.