Legro, R. S., & Strauss, J. F. (2002). Molecular progress in infertility: polycystic ovary syndrome. Fertility and Sterility, 78(3), 569-576. https://doi.org/10.1016/s0015-0282(02)03275-2
Legro, Richard S., and Jerome F. Strauss. "Molecular progress in infertility: polycystic ovary syndrome." Fertility and Sterility, vol. 78, no. 3, 2002, pp. 569-576.
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Penn State Milton S. Hershey Medical Center01h22ap11
PCOS clusters in families, but no gene has been confirmed
A 2002 literature review of family, cell, and gene studies finds that polycystic ovary syndrome (PCOS) clusters in families, with an inheritance pattern still uncertain. PCOS also carries the name PMOS (Polyendocrine Metabolic Ovarian Syndrome). The authors report that no gene has been pinpointed as its cause.
Key Findings
The authors judge that family studies strongly suggest PCOS runs in families, and that the inheritance seen is consistent with a dominant pattern.
Nearly 50% of the sisters of women with PCOS had raised testosterone, total or bioavailable. The authors say this suggests high androgens are a dominant trait.
The largest available twin study contacted 500 female twins and analyzed 34 pairs. Twins showed high discordance for polycystic ovaries and greater concordance for biochemical measures.
Theca cells from women with PCOS, grown through multiple population doublings, showed greater steroidogenic activity than theca cells from normal ovaries.
A region near the insulin receptor gene (19p13.3) was linked or associated with PCOS in two independent studies. The responsible gene remains to be identified.
Interpretation
The paper reviews published studies, so its strength depends on the studies it gathers. The authors note that the family studies used different diagnostic criteria. Several candidate gene findings, including CYP17 and follistatin, weakened in larger follow-up work. The authors write that routine screening for the rare associated variants is not indicated at this time.
RRM Context
The review describes PCOS as a condition spanning the ovary, the adrenal glands, and insulin signaling, with many possible origins. Restorative reproductive medicine starts with root-cause evaluation. Varied origins fit that approach, since the same diagnosis can come from different drivers in each woman.
Our editorial summary of this paper, not the article's abstract.
Abstract
Objective
To review the evidence that polycystic ovary syndrome is a genetic disease.
Design
Review of published literature.
Results
The existing literature provides a strong basis for arguing that PCOS clusters in families. However, the mode of inheritance of the disorder is still uncertain, although the majority of studies are consistent with an autosomal dominant pattern, modified perhaps by environmental factors. In addition, studies on PCOS cells (theca, muscle, and adipocytes) in culture have documented a persistent biochemical and molecular phenotype that distinguishes them from normal cells. Although several loci have been proposed as PCOS genes including CYP11A, the insulin gene, and a region near the insulin receptor, the evidence supporting linkage is not overwhelming. The strongest case can be made for the region near the insulin receptor gene, as it has been identified in two separate studies. However, the responsible gene at chromosome 19p13.3 remains to be identified. Association studies have provided a number of potential loci with genetic variants that may create or add to a PCOS phenotype, including Calpain 10, IRS-1 and -2, and SHBG.
Conclusions
Collectively, these findings are consistent with the concept that a gene or several genes are linked to PCOS susceptibility. Because the mutations/genotypes associated with PCOS are rare, and their full impact on the phenotype incompletely understood, routine screening of women with PCOS or stigmata of PCOS for these genetic variants is not indicated at this time. Currently the treatment implications for individually identified genetic variants is uncertain and must be addressed on a case by case basis.
PMOS / PCOS has four diagnostic phenotypes and distinct metabolic, reproductive, and mental health implications. How RRM-trained clinicians approach diagnosis and treatment differently.
