Serum anti-Mullerian hormone levels during controlled ovarian hyperstimulation in women with polycystic ovaries with and without hyperandrogenism

BACKGROUND: Anti-Mullerian hormone (AMH) is expressed in pre- and small-antral follicles. High serum levels are found in women with polycystic ovaries (PCO), accordant with their increased content of small follicles. To evaluate the relationship between AMH, folliculogenesis and hyperandrogenism, we compared serum AMH levels between women with PCO with and without hyperandrogenism and normal controls during controlled ovarian hyperstimulation (COH). METHODS: Nineteen women with PCO and hyperandrogenism (group A), 10 women with PCO but no hyperandrogenism (group B) and 23 ovulatory women with normal ovarian morphology (group C, controls) underwent COH with the long protocol. Serum levels of AMH, estradiol, androstenedione and follicular tracking were determined before gonadotropins treatment (day 0) and every 2-4 days up to the day of HCG administration. RESULTS: AMH levels declined gradually throughout COH in the three groups, but remained higher in groups A and B compared with the controls. Significantly higher levels were found in group A compared with group B, despite comparable numbers of small follicles. Multiple regression analysis revealed that both the number of small follicles and serum androgens were correlated to AMH. CONCLUSIONS: Women with PCO have higher serum AMH levels during COH than controls. Hyperandrogenism is associated with an additional increase in AMH. It is conceivable that hyperandrogenism may reflect more severe disruption of folliculogenesis in women with PCO or may affect AMH secretion.     

Abnormalities in the serum insulin-like growth factor-1 axis in women with hyperandrogenism

Objective: To study the insulin-like growth factor-1 (IGF-1) axis in hirsute women.

Design: Controlled clinical study.

Setting: Tertiary care institutional hospital.

Patient(s): Forty hirsute women and 17 women with normal menstrual cycles.

Intervention(s): Basal and ACTH-stimulated samples were obtained, and sampling was repeated 1 (gonadal stimulation) and 21 (gonadal suppression) days after a single 3.75-mg IM dose of triptorelin. Controls did not receive triptorelin for ethical reasons.

Main Outcome Measure(s): Serum GH, IGF-1, IGF-binding protein-3 (IGFBP-3), insulin, glucose, total testosterone, sex hormone-binding globulin, E₂, and gonadotropin levels. Basal and ACTH-stimulated steroid precursors were measured.

Result(s): Patients with idiopathic hirsutism were identified by normal serum androgen levels (n = 17). Those with functional ovarian hyperandrogenism (n = 15) were identified by an increase in the serum testosterone level that normalized during gonadal suppression, whereas those with functional adrenal hyperandrogenism (n = 8) were identified by an initial increase in the testosterone level that persisted during gonadal suppression. The adrenal hyperandrogenism group had increased IGF-1 levels compared with the control, idiopathic hirsutism, and ovarian hyperandrogenism groups. Patients with ovarian hyperandrogenism had normal IGF-1 concentrations, but their IGFBP-3 concentrations were lower than those of controls. No differences were observed in GH levels between any of the groups. These results persisted when the influence of age was corrected for.

Conclusion(s): The IGF-1 axis appears to be involved in the pathogenesis of hyperandrogenism, especially in patients with adrenal hyperandrogenism, who have a clear increase in IGF-1 levels. Moreover, patients with ovarian hirsutism have decreased IGFBP-3 concentrations, which might enhance IGF-1 bioavailability.     

Long-term satisfaction and tolerability with low-dose flutamide: a 20-year surveillance study on 120 hyperandrogenic women

Objective: To evaluate the long-term safety, satisfaction and tolerability of flutamide therapy for female hyperandrogenism.

Design: A 20-year surveillance study.

Methods: Setting: Gynecology Department in a teaching hospital. Patients: Hyperandrogenic women complaining for hirsutism treatment were followed between February 1995 and April 2015. Interventions: Women received flutamide 125 or 250?mg/day alone (n?=?55) or combined with oral contraceptives (n?=?65). Main outcome measures: Adverse events, safety, tolerability satisfaction and efficacy were assessed every 6 months during all the follow-up. Lab tests including liver and lipid profiles were also recorded in each control.

Results: Patients under flutamide therapy showed significant improvements in hirsutism scores after 6 months of treatment with a maximum effect at 12 months that was maintained during all the therapy time. Satisfaction reported by patients with the efficacy of the drug in a visual scale was also high. A total of 54.2 % women presented one or more adverse effects during the follow-up; 33.3% showed at least one adverse effect possibly related with the study drug; and 24.1% withdrew from the study because of adverse effects. During the follow-up, as many as 89.9 % of patients abandoned flutamide. Reasons include: questions linked to medical problems (50%), attempt pregnancy (4%) and significant improvement in the symptomatology (35.8%).

Conclusions: Flutamide is very effective for hirsutism treatment; however, adverse effects are very frequent and affect compliance.     

Abnormal linear growth in paediatric adrenal diseases: Pathogenesis,prevalence and management

Abnormal adrenal function can interfere with linear growth, potentially causing either acceleration or impairment of growth in paediatric patients. These abnormalities can be caused by direct effects of adrenal hormones, particularly glucocorticoids and sex steroids, or be mediated by indirect mechanisms such as the disturbance of the growth hormone-insulin-like growth factor-1 axis and aromatization of androgens to oestrogens. The early diagnosis and optimal treatment of adrenal disorders can prevent or minimize growth disturbance and facilitate improved height gain. Mechanisms of growth disturbance in the following abnormal states will be discussed; hypercortisolaemia, hyperandrogenaemia and obesity. Prevalence and features of growth disturbance will be discussed in ACTH-dependent and ACTH-independent Cushing's syndrome, adrenocortical tumours, premature adrenarche, congenital adrenal hyperplasia and adrenal insufficiency disorders. Recommendations for management have been included.     

Adolescent ovarian thecoma presenting as progressive hyperandrogenism: case report and review of the literature

Abstract

Hyperandrogenism is frequent and under investigated in adolescent girls. A 15-year-6-month-old French girl presented with oligomenorrhea and slowly progressing virilization 2?years post-menarche. Medical history revealed prenatal pesticide exposure through maternal professional activity and recurrent premature thelarche. Severe hirsutism, mild facial acne and clitoromegaly were noted. Serum androgens (testosterone: 94?ng/dL, 4-androstenedione: 8.23?ng/mL) were high and non-classic 21-hydroxylase deficiency was excluded. Pelvic ultrasonography showed a left ovarian mass, confirmed by computed tomography scan. Tumor markers were negative. Laparoscopic surgery was performed. The pathological diagnosis was benign luteinized thecoma. Postoperatively, the menstrual cycle and serum androgens became normal and hirsutism slowly improved. Hyperandrogenism 2?years after menarche should be systematically investigated, even if slowly progressive, since it may be a symptom of a rare virilizing ovarian tumor, like thecoma.     

Role of the Pentanucleotide （tttta）n Polymorphisms of CYP11a Gene in the Pathogenesis of Hyperandrogenism in Chinese Women with Polycystic Ovary Syndrome

To determine the (tttta)n repeat polymorphisms at the promoter region of CYP11a gene, and study its linkage to hyperandrogenism of polycystic ovary syndrome (PCOS) in Chinese women, a case-control study was conducted in the Reproductive Medical Center of the Second Affiliated Hospital of Zhengzhou University (Zhengzhou, China). 96 PCOS patients and 78 healthy control women were included. CYP11a (tttta)n repeat-polymorphism genotyping analysis was performed by using polymerase chain reaction (PCR). Serum pituitary hormone and total testosterone levels were measured by ELISA. 4 different CYP1 la (tttta)n allelles were identified, corresponding to 4-, 6-, 8-, and 9-repeat-unit alleles. The frequency and distribution of these alleles are 0. 16, 0.33, 0.38, and 0. 13 respectively in PCOS patients, as compared with 0. 20, 0. 34, 0. 35, and 0.11 respectively in healthy controls. There were no significant differences between these two groups. Moreover, no correlation between the polymorphism of CYP11a gene and serum testosterone level of patients with PCOS and controls was observed. It is concluded that microsatellite polymorphism (tttta)n of gene CYP11a exists in Chinese women and the polymorphism of CYP11a gene does not play an important role in the pathogenesis of Chinese patients with PCOS, especially in patients with hyperandrogenism.     

Ovarian hyperandrogenism in adult female rhesus monkeys exposed to prenatal androgen excess.

OBJECTIVE: To determine whether there is an ovarian thecal cell component to hyperandrogenism exhibited in adult female rhesus monkeys exposed to androgen excess during prenatal life. DESIGN: Prospective nonrandomized study. SETTING: An academic research environment. ANIMAL(S): Eleven adult female rhesus monkeys. INTERVENTION(S): Five female rhesus monkeys exposed prenatally to T propionate and six normal females underwent blood sampling immediately before and 24 h after a 200-IU IM injection of recombinant hCG. MAIN OUTCOME MEASURE(S): Serum T, 17alpha-hydroxyprogesterone, DHEAS, and cortisol concentrations determined by RIA. RESULT(S): Prenatally androgenized females exhibited increased T and 17alpha-hydroxyprogesterone response to recombinant hCG stimulation, compared to control females. Although serum adrenal DHEAS concentrations were elevated in comparison to control females, the increased levels of DHEAS were not dependent on recombinant hCG stimulation. CONCLUSION(S): Prenatal androgen excess in female rhesus monkeys causes perturbations in ovarian and adrenal steroidogenesis during adulthood, which may both contribute to hyperandrogenism.