Menstrual Cycle Markers of Ovarian Aging and Sex Steroid Hormone Genotypes

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Abstract

We related variation in 4 sex steroid genes to 3 phenotypic indicators of ovarian aging, including no evidence of luteal activity as a marker of anovulatory cycles, shorter or longer menstrual cycle lengths, and the profiles of metabolites of estrogens, progesterone, follicle-stimulating hormone, and luteinizing hormone measured in urine samples collected daily across a menstrual cycle in women aged 43 to 53 years. The study sample included 485 menstruating women without hormone therapy who had collected daily urine hormone samples across 1 menstrual cycle or 50 days, whichever occurred first. There were 14 single nucleotide polymorphisms from 4 genes, including estrogen receptor-α (ESR1), estrogen receptor-β, aromatase, and 17β hydroxysteroid dehydrogenase type 1, related to ovarian aging phenotypes that include the presence or absence of luteal activity, menstrual cycle lengths < or > 24 to 31 days, and profiles of urinary hormone metabolites. Women with the TT genotype of ESR1 rs3798577 have evidence of advanced ovarian aging compared with women with the CT or CC genotypes, after adjustment for race/ethnicity, chronologic age, and race/ethnicity-specific body mass index. Further, women with the TC and CC genotypes of ESR1 rs2234693 may have a greater likelihood of more advanced ovarian aging than do women with the TT genotype, adjusting for covariates. Using a candidate gene approach, 2 ESR1 polymorphisms are related to 3 phenotypic markers of ovarian aging, suggesting a possible role for the ESR1 gene in the timing of the menopausal transition. © 2006 Elsevier Inc. All rights reserved.

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Sowers, M. F. R., Jannausch, M. L., McConnell, D. S., Kardia, S. R., & Randolph, J. F. (2006). Menstrual Cycle Markers of Ovarian Aging and Sex Steroid Hormone Genotypes. American Journal of Medicine, 119(9 SUPPL. 1). https://doi.org/10.1016/j.amjmed.2006.07.004

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