gestodene and Hirsutism

We studied (1) the effects of oral contraceptive pills (OCPs) on hirsutism, hormonal and metabolic variables in 49 polycystic ovary syndrome patients without metabolic comorbidities and (2) the effect of 17-hydroxysteroid dehydrogenase type 5 gene polymorphism (-71A/G HSD17B5 SNP) on the response to OCP treatment. Mean age was 21.9 ± 6.5 years. Patients received monophasic OCP (20 μg ethinyl estradiol plus 75 μg gestodene), 21/28 days per cycle, during 6 months; 32 patients with severe hirsutism also received spironolactone 100 mg. The frequencies of HSD17B5 genotypes were: AA = 0.49 (55.1%), AG = 0.42 (30.6%) and GG = 0.09 (14.3%). After 6 months, body mass index and waist circumference remained unchanged regardless of the presence of allele G. A slight reduction (p < 0.05) was noted in systolic blood pressure (p < 0.05) and luteinizing hormone levels, whereas a slight increase (p < 0.05) was noted in lipids. Total testosterone and hirsutism score declined, while sex hormone binding globulin increased after OCP treatment (p < 0.05). None of these changes were associated with genotype. Insulin and homeostasis model assessment remained unchanged after treatment and did not vary according to the presence of allele G. OCP seems to ameliorate androgenic symptoms without compromising metabolic parameters. The -71A/G SNP of HSD17B5 gene did not contribute to the improvements observed.

Topics: 3-Hydroxysteroid Dehydrogenases; Adolescent; Adult; Aldo-Keto Reductase Family 1 Member C3; Brazil; Contraceptives, Oral, Combined; Drug Therapy, Combination; Ethinyl Estradiol; Female; Genetic Association Studies; Hirsutism; Humans; Hydroxyprostaglandin Dehydrogenases; Hyperandrogenism; Mineralocorticoid Receptor Antagonists; Norpregnenes; Pilot Projects; Polycystic Ovary Syndrome; Polymorphism, Single Nucleotide; Severity of Illness Index; Sex Hormone-Binding Globulin; Spironolactone; Testosterone; Young Adult

Hyperandrogenism is a condition affecting 5-10% of adolescents. The aim of this study was to evaluate the efficacy of very low dose of flutamide in the treatment of hyperandrogenism in adolescence. One hundred and fifty-eight patients, presenting severe acne and/or hirsutism, received 62.5 mg/day of flutamide + ethinylestradiol + gestodene for 18 months. The patients were subjected to assessments of hepatic enzymes levels. Thirty subjects treated with drospirenone + ethinylestradiol represented the control group. After 18 months of treatment, it was obtained a decrease of hirsutism (-39.9%), an almost recovery of acne (98% of patients) with better results of those obtained in control group. Only one case of light hypertransaminasemia was recorded, regressed spontaneously. Very low dose of flutamide was successful and safe and in the treatment of hyperandrogenism in adolescence.

Topics: Acne Vulgaris; Adolescent; Androgen Antagonists; Androstenes; Dose-Response Relationship, Drug; Drug Therapy, Combination; Ethinyl Estradiol; Female; Flutamide; Hirsutism; Humans; Hyperandrogenism; Norpregnenes; Treatment Outcome; Young Adult

To assess whether a single nucleotide polymorphism (SNP50) of the aromatase gene (CYP19) is associated with polycystic ovary syndrome (PCOS) phenotypes and to investigate the influence of this polymorphism on the response of PCOS to treatment with oral contraceptive pills (OCP).. 162 hirsute women were stratified into a classic PCOS group (hyperandrogenism, ovulatory dysfunction, c-PCOS) and an ovulatory PCOS group (hyperandrogenism, ovulatory cycles, polycystic ovaries, ov-PCOS). 51 women completed a 6-month OCP trial (20 µg ethinyl estradiol + 75 µg gestodene, 21/28 days per cycle, plus 100 mg spironolactone in 32 women with moderate to severe hirsutism). We considered the presence of the polymorphic allele A (AG+AA) in comparison to the absence of the polymorphism (GG) to express results and to perform the comparisons regarding clinical variables.. Mean age was 23.3 ± 6.9 years. Hirsutism score was similar in c-PCOS and ov-PCOS (15 (11-20) vs. 13 (11-20)). The differences in hormone and metabolic variables between phenotypes were independent of the presence of allele A. In the OCP trial subsample, no differences were observed between genotypes after 6 months' treatment.. The differences between c-PCOS and ov-PCOS cannot be explained by the genetic variation at SNP50 in the CYP19 gene.

Topics: Adult; Androgens; Anovulation; Aromatase; Blood Pressure; Body Mass Index; Contraceptives, Oral; Ethinyl Estradiol; Female; Gene Frequency; Genotype; Hirsutism; Humans; Hyperandrogenism; Norpregnenes; Phenotype; Polycystic Ovary Syndrome; Polymorphism, Single Nucleotide; Spironolactone; Young Adult

A case of unusual combination of polycystic ovaries (PCO), adrenal non-functioning adenoma and severe hirsutism in a young woman from Southern Italy is reported here. A 18-yr-old woman was referred to our Department because of oligomenhorrea, acne and severe hirsutism. During evaluation of the cause of her symptoms, PCO and small left adrenal adenoma were revealed. Although adrenal androgen excess has been shown to dysregulate the hypothalamic-pituitary-gonadal axis, causing PCO-like syndrome, normal circulating androgen values were found. Androgens and cortisol levels were completely suppressed by low-dose dexamethasone test, excluding autonomous steroid secretion by the adrenal mass. Normal response of cortisol and adrenal androgens to corticotropin stimulation test permitted the exclusion of functional adrenal hyperandrogenism. Despite normal LH/FSH ratio, anovulatory cycles were revealed by persistently low progesterone values. Glucose and insulin response to oral glucose tolerance test did not differ from those of normal population. The patient showed an improvement of acne and hirsutism on therapy with estro-progestins (EP). In conclusion, despite normal pattern of serum androgens and LH/FSH ratio, this patient had anovulatory cycles and good response to the EP treatment. These findings suggest that ultrasonography evidence of PCO together with anovulatory cycles contributed to her clinical picture whereas adrenal adenoma seemed to have no relevant role. This case report underlines the need of cautious interpretation of imaging results and clinical signs of severe hirsutism, reminding one that the true cause of a medical problem may not be the most evident.

Topics: Acne Vulgaris; Adenoma; Adolescent; Adrenal Gland Neoplasms; Androgens; Estrogens; Ethinyl Estradiol; Female; Hirsutism; Humans; Norpregnenes; Oligomenorrhea; Ovary; Polycystic Ovary Syndrome; Progestins; Treatment Outcome; Ultrasonography

Using an ultrasensitive assay, prostate-specific antigen (PSA) has been detected in female serum and has been proposed as a potential marker of androgen excess in hirsute women. Measurement of PSA levels in serum may play a role in monitoring hirsutism during antiandrogen therapy. We investigated the role of PSA as a marker of androgen activity in hirsute patients taking spironolactone together with oral contraceptive pills containing ethinyl estradiol and gestodene. Twenty-eight hirsute patients were included in the study. Clinical and biochemical variables including serum levels of PSA (using an ultrasensitive chemiluminscent immunoassay), dehydroepiandrosterone sulfate, total testosterone, free testosterone and 17-hydroxyprogesterone concentrations were recorded at baseline and after six cycles of treatment. Fifteen healthy women were included in the study as controls. Serum PSA levels in hirsute women were clearly higher than in the control group (0.023 +/- 0.004 vs. 0.006 +/- 0.003 ng/ml, p < 0.001) and correlated with baseline serum free testosterone concentrations (r = 0.518, p = 0.005). After 6 months, serum PSA concentrations as compared with baseline values did not change significantly in patients who were given spironolactone plus contraceptive pills (p = 0.4) despite a marked decrease in total testosterone, free testosterone, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate and hirsutism score (p < 0.05). Thus, serum PSA levels in hirsute women were higher than in non-hirsute healthy controls. A 6-month course of treatment with spironolactone combined with contraceptive pills containing ethinylestradiol and gestodene did not reduce high serum PSA levels in these subjects. In conclusion, the serum PSA level is not a convenient biochemical marker with the available assays for the management of hirsute women treated with the combination of spironolactone and oral contraceptives.

Topics: 17-alpha-Hydroxyprogesterone; Adult; Biomarkers; Body Mass Index; Contraceptives, Oral; Dehydroepiandrosterone Sulfate; Drug Therapy, Combination; Ethinyl Estradiol; Female; Hirsutism; Humans; Norpregnenes; Prostate-Specific Antigen; Spironolactone; Testosterone