Objective: The aim of this study was to investigate serum lipid and hormone levels in women withpremature ovarian

failure (POF) and compare them with those of healthy women of similar age. Methods: We measured fasting total cholesterol (TC), triglyceride, low-density lipoprotein (LDL), highdensity lipoprotein, estradiol (E2), follicle-stimulating hormone (FSH), progesterone, and testosterone levels in 47 women with POF not using any hormone therapy and 60 healthy women of the same age range not using oral contraceptives or any other hormonal medication. Results: There were no statistically significant differences between the groups in terms of age, body mass index (BMI) and smoking status (P = 0.054, 0.250, and 0.656, respectively). The mean E2 levels of the POF and control groups were 27.9 +/- 2.3 and 87.8 +/- 75.2 pg/mL, respectively (P < 0.001). Women with POF presented with significantly higher TC and LDL levels (P = 0.006 and 0.040, respectively). However, no difference was found between the groups with regard to triglyceride and high-density lipoprotein levels (P = 0.128 and 0.062, respectively). We determined that there was a significant negative correlation between E2 and TC levels (r = -0.291, P = 0.047) in the POF group. However, no correlation could be identified between E2 and lipids in the control group. Likewise, no correlation was present between FSH and lipids in both groups. We divided the control group according to basal FSH level. Group A consisted of the women with a serum FSH level lower than 7 IU/L, and group B consisted of the women with a serum FSH level of 7 IU/L or higher. There was no difference between the groups in age, body mass index, E2 concentration, and smoking status. The FSH level of group A was significantly lower than that of group B (P < 0.001). We found no difference between groups A and B with regard to lipid levels. Conclusions: Higher TC and LDL levels in women with POF compared with the control group suggest that estrogen deprivation in women with POF leads to unfavorable lipid changes.

BACKGROUND: Elucidation of the causes of premature ovarian failure (POF) is difficult due to the heterogeneity of the condition. Inhibin is a potential candidate gene for POF based on its dual actions on FSH secretion by the pituitary and gametogenesis in the gonads. A missense mutation in the inhibin [alpha] subunit gene (INHA G769A) is associated with POF in several populations. However, there is phenotypic heterogeneity in INHA G769A mutation carriers. Baja fsh andrgenos TECA METHODS: Relevant studies were identified by searching PubMed and mutational frequencies combined for meta-analysis. RESULTS: Meta-analysis of published studies revealed a risk difference of 0.04 (-0.030 to 0.11). The occurrence of asymptomatic carriers in populations suggests incomplete penetrance and/or a multigenetic cause of POF. We propose that a decline in inhibin bioactivity caused by the mutation could increase FSH levels; and in a susceptible individual, the heightened sensitivity to gonadotrophins causes POF. Impaired paracrine effects of inhibin could impact folliculogenesis due to reduced antagonism of activin, bone morphogenetic protein 15 and growth differentiation factor 9. Functional studies of this mutation indicate normal production of dimeric inhibin A and B and impaired bioactivity of inhibin B.

CONCLUSIONS: The identification of an autosomal mutation in the inhibin [alpha] subunit gene that is significantly linked to POF in certain ethnic populations highlights the role of inhibin in the regulation of ovarian biology and fertility. Although the reduction of inhibin B bioactivity by the INHA G769A mutation is clearly not the only cause, evidence suggests that this change may serve as a susceptibility factor, increasing the likelihood of POF.