The phenotype of polycystic ovary syndrome ameliorates with aging.

OBJECTIVE: To assess the effects of aging on the features of polycystic ovary syndrome (PCOS). DESIGN: Retrospective longitudinal follow-up study. SETTING: Tertiary care center. PATIENT(S): Patients with PCOS, diagnosed according to the 2003 Rotterdam criteria, who visited the outpatient clinic on consecutive occasions with a minimum interval of 6 months. INTERVENTION(S): Comparisons were made between the first visit and the consecutive visit grouped by intervals. MAIN OUTCOME MEASURE(S): Changes in clinical and endocrine characteristics. RESULT(S): A total of 254 women visited the outpatient clinic on 2 occasions each. Consecutive visits were grouped into 0.5 to 3.9 years (n = 172; mean follow-up, 2.6 years) and 4.0 to 7.0 years (n = 82; mean follow-up, 5.5 years). At their second visit, significantly more women had regained a regular cycle. The total antral follicle count was similar. Serum levels of testosterone, androstenedione, and dehydroepiandrosterone sulfate had decreased significantly. Plasma glucose levels had increased, whereas serum insulin levels and homeostasis model assessment score had significantly decreased. CONCLUSION(S): The PCOS phenotype changed with aging, suggesting an amelioration of the phenotype and ovarian dysfunction as indicated by the increase in number of regular menstrual cycles, decrease in serum androgen levels, and decrease in insulin resistance.

Oligoovulatory and anovulatory cycles in women with polycystic ovary syndrome (PCOS): what's the difference?

CONTEXT: Polycystic ovary syndrome (PCOS) is a heterogeneous disorder. The phenotype may differ between patients who exhibit signs of recent ovulation and anovulatory PCOS patients. OBJECTIVE: Our objective was to study differences in clinical and endocrine characteristics and response to ovulation induction (OI) treatment comparing oligoovulatory and anovulatory PCOS patients. DESIGN AND SETTING: We conducted a retrospective cohort study at a tertiary hospital. PATIENTS: PCOS patients (n=1750) presenting with oligo- or amenorrhea were diagnosed according to the Rotterdam 2003 consensus criteria. Arbitrarily, oligoovulatory PCOS was defined by a single random serum progesterone level of 10 nmol/liter or higher. MAIN OUTCOME MEASURES: We evaluated the incidence of oligo- or amenorrhea, menstrual cycle length, serum androgen levels, follicle count, and OI outcome parameters. RESULTS: Anovulatory women (n=1541 of 1750, 88.1%) were more often amenorrheic (P<0.001) and presented with a longer cycle duration (P<0.001) compared with oligoovulatory women (n=209 of 1750, 11.9%). Serum levels of testosterone (P<0.001), the free androgen index (P<0.001), and total follicle count (P<0.005) were higher in anovulatory compared with oligoovulatory patients. During clomiphene citrate OI, more oligoovulatory women gained regular menstrual cycles (P<0.05), whereas after second-line treatment with recombinant FSH, more anovulatory women became pregnant (P<0.05). CONCLUSIONS: Oligoovulatory women with PCOS exhibit a milder phenotype of ovarian dysfunction and have a more favorable response to OI treatment using clomiphene citrate compared with anovulatory PCOS patients. However, during second-line treatment with recombinant FSH, anovulatory PCOS patients presented with a higher chance of pregnancy compared with oligoovulatory patients.

A functional anti-mullerian hormone gene polymorphism is associated with follicle number and androgen levels in polycystic ovary syndrome patients.

CONTEXT: The common characteristic of polycystic ovary syndrome (PCOS) is a disturbance in the selection of the dominant follicle, resulting in anovulation. In PCOS women, serum anti-Müllerian hormone (AMH) levels are elevated. Because AMH decreases FSH sensitivity in mice, the elevated AMH levels may contribute to the disturbed follicle selection in PCOS women. OBJECTIVE: The objective of the study was to investigate the role of the AMH signaling pathway in the pathophysiology of PCOS using a genetic approach. DESIGN: The association of the AMH Ile(49)Ser (rs10407022) and the AMH type II receptor -482 A>G (rs2002555) polymorphism with PCOS susceptibility and phenotype was studied in a large cohort of PCOS women. SETTING/SUBJECTS: A total of 331 women with PCOS, 32 normoovulatory controls, and 3635 population-based controls were included. MAIN OUTCOME MEASURES: Ovarian parameters, serum AMH, FSH, androgen, and estradiol levels were measured. RESULTS: Genotype and allele frequencies for the AMH Ile(49)Ser and AMH type II receptor -482 A>G polymorphism were similar in PCOS women and controls. However, within the group of PCOS women, carriers of the AMH (49)Ser allele less often had polycystic ovaries (92.7 vs. 99.5%, P = 0.0004), lower follicle numbers (P = 0.03), and lower androgen levels, compared with noncarriers (P = 0.04). In addition, in vitro studies demonstrated that the bioactivity of the AMH (49)Ser protein is diminished, compared with the AMH (49)Ile protein (P < 0.0001). CONCLUSIONS: Genetic variants in the AMH and AMH type II receptor gene do not influence PCOS susceptibility. However, our results suggest that the AMH Ile(49)Ser polymorphism contributes to the severity of the PCOS phenotype.

Anti-Müllerian hormone and anti-Müllerian hormone type II receptor polymorphisms are associated with follicular phase estradiol levels in normo-ovulatory women.

BACKGROUND: In mice, anti-Müllerian hormone (AMH) inhibits primordial follicle recruitment and decreases FSH sensitivity. Little is known about the role of AMH in human ovarian physiology. We hypothesize that in women AMH has a similar role in ovarian function as in mice and investigated this using a genetic approach. METHODS: The association of the AMH Ile(49)Ser and the AMH type II receptor (AMHR2) -482 A > G polymorphisms with menstrual cycle characteristics was studied in a Dutch (n = 32) and a German (n = 21) cohort of normo-ovulatory women. RESULTS: Carriers of the AMH Ser(49) allele had higher serum estradiol (E(2)) levels on menstrual cycle day 3 when compared with non-carriers in the Dutch cohort (P = 0.012) and in the combined Dutch and German cohort (P = 0.03). Carriers of the AMHR2 -482G allele also had higher follicular phase E(2) levels when compared with non-carriers in the Dutch cohort (P = 0.028), the German cohort (P = 0.048) and hence also the combined cohort (P = 0.012). Women carrying both AMH Ser(49) and AMHR2 -482G alleles had highest E(2) levels (P = 0.001). For both polymorphisms no association with serum AMH or FSH levels was observed. CONCLUSIONS: Polymorphisms in the AMH and AMHR2 genes are associated with follicular phase E(2) levels, suggesting a role for AMH in the regulation of FSH sensitivity in the human ovary.