P-443 Resumption of ovulation during lifestyle intervention in anovulatory women with PCOS and obesity is associated with reduction of serum AMH and androgens concentrations

Abstract Study question Are there differences in AMH and androgens concentrations between women with PCOS who resume ovulation (RO+) and those remain anovulatory (RO-) during lifestyle intervention? Summary answer RO+ women showed significant decrease in AMH and 11β-hydroxyandrostenedione concentrations at three months, and increase in SHBG concentrations at six months compared to RO- women. What is known already Lifestyle interventions have been shown to reduce clinical and biochemical hyperandrogenism in women with PCOS. Weight loss of 5-10% may reverse anovulatory status, thereby increasing natural conception rates. However, the underlying mechanisms why some women with PCOS remain anovulatory and others resume ovulation after weight loss are unclear. Reproductive characteristics at baseline and a greater degree of change in endocrine and metabolic features with lifestyle intervention may be crucial for ovulatory response. Study design, size, duration We used data and samples originating from an RCT which examined the efficacy of a six-month lifestyle intervention prior infertility treatment compared to prompt infertility treatment on live birth rate in women with obesity. In total of 577 women with obesity were randomized between 2009 and 2012. Anovulatory women with PCOS who were allocated to the intervention arm of the original RCT (n = 97) were included in the current analysis. Participants/materials, setting, methods We defined women as ovulatory during or after intervention based on the following criteria either: (1) spontaneous pregnancy; Or (2) Treatment strategy after lifestyle intervention; expectant management; (3) or IUI treatment in natural cycles. The steroid hormones were measured using LC-MS/MS. Multilevel analysis with the adjustment of baseline measurements was used to examine differences in changes in AMH and androgens concentrations between RO + (n=34) and RO- groups (n = 61) at three and six months after intervention. Main results and the role of chance At baseline, the mean age was 27.5 ± 3.6 in RO+ group and 27.9 ± 4.1 years in RO- group (p = 0.65). The mean weight was 101.2 ± 9.5 and 105.0 ± 14.6 kg, respectively (p = 0.13). AMH concentrations showed significant differences between RO+ women and RO- women (median and IQR 4.7 [3.2; 8.3] in the RO+ group and 7.2 [5.3; 10.8] ng/mL in the RO- group, p = 0.03). Androgen concentrations did not differ between the two groups. During and after lifestyle intervention, RO+ women had significant decrease in AMH (mean difference: –1.6 ng/mL, 95%CI: –3.0 to –0.20, p = 0.03) and 11β-hydroxyandrostenedione (mean difference: –1.7 nmol/L, 95%CI: –3.1 to –0.41, p = 0.01) concentrations than RO- women at three months. SHBG concentrations were significantly increased in RO+ compared to RO- women at six months (mean difference: 11 nmol/L, 95%CI: 1.1 to 22, p = 0.03). Changes in 11-ketotestosterone (three months mean difference: –0.15 nmol/L, 95%CI: –0.49 to 0.20, p = 0.41; six months: –0.39 nmol/L, 95%CI: –1.3 to 0.57, p = 0.43) and testosterone (three months mean difference: 0.13 nmol/L, 95%CI: –0.32 to 0.57, p = 0.58; six months: –0.29 nmol/L, 95%CI: –0.81 to 0.23, p = 0.27) did not differ at three or six months between groups. Limitations, reasons for caution The indirect parameters to confirm ovulatory cycles at the end of lifestyle program and small sample size may limit the robustness of the results. Wider implications of the findings Reduction of serum AMH and androgen concentrations during lifestyle intervention is associated with recovery of ovulatory cycles. When our results are confirmed in other studies, serum AMH and androgens concentrations could be monitored during lifestyle intervention to provide individualized recommendations on resumption of ovulatory cycles in anovulatory women with PCOS. Trial registration number NTR1530