Objective: Premature ovarian failure (POF) is characterized by secondary amenorrhea before the age of 40 years, along with repeated increased follicle-stimulating hormone and low estrogen concentrations. POF is considered a complex genetic disease with a familial presentation in 12% to 50% of cases. POF may originate from different genes and various gene-environment interactions. The aim of this study was to identify possible differences in phenotype comparing women with familial and women with sporadic POF. Methods: A multicenter study was initiated in the Netherlands using standardized phenotyping. For each woman, medical history, menstrual cycle, and fertility and smoking status were assessed and a standardized examination was performed. Based on a detailed three-generation family history, women were identified as having either familial (defined as having at least one relative with POF) or sporadic POF. Results: A total of 58 familial cases and 142 sporadic cases of POF were identified. Maternal age at menopause was significantly lower in the women with familial compared with the women with sporadic POF (41.0 ± 7.5 and 49.7 ± 2.6 y, respectively; P < 0.001). Sex hormone-binding globulin concentration was significantly higher in the women with familial than in the women with sporadic POF (73.6 ± 37.1 and 55.2 ± 26.9 nmol/L, respectively; P = 0.002). All other characteristics, such as parity, bone mineral density, and serum follicle-stimulating hormone and lipid levels were similar, as was the incidence of autoimmunity and cytogenetic abnormalities. Conclusions: Familial and sporadic POF do not differ in phenotype except for maternal menopause age and sex hormone-binding globulin concentration. Future studies are needed to unravel the genotype-phenotype interactions in POF.

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doi.org/10.1097/gme.0b013e3181cf8521, hdl.handle.net/1765/64292
Department of Gynaecology & Obstetrics

Janse, F., Knauff, E., Niermeijer, M., Eijkemans, R., Laven, J., Lambalk, C., … Goverde, A. (2010). Similar phenotype characteristics comparing familial and sporadic premature ovarian failure. Menopause, 17(4), 758–761. doi:10.1097/gme.0b013e3181cf8521