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J Clin Endocrinol Metab. 2008 Jul;93(7):2909-12. doi: 10.1210/jc.2008-0403. Epub 2008 Apr 29.

Association of CYP3A7*1C and serum dehydroepiandrosterone sulfate levels in women with polycystic ovary syndrome.

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  • 1Department of Obstetrics/Gynecology and Center for Androgen Related Disorders, Cedars-Sinai Medical Center, 8635 West Third Street, Los Angeles, CA 90048, USA.

Abstract

CONTEXT:

Adrenal androgen excess is common in polycystic ovary syndrome (PCOS) and appears to be heritable. CYP3A7 metabolizes dehydroepiandrosterone and its sulfate (DHEAS). A promoter variant, CYP3A7*1C, which results in persistent expression in adults, was associated with reduced DHEAS levels in a previous study, which led us to consider CYP3A7*1C as a modulator of adrenal androgen excess in patients with PCOS.

OBJECTIVE:

The objective was to replicate the association between CYP3A7*1C and reduced DHEAS levels in PCOS patients and assess its possible role in modulating testosterone levels.

DESIGN:

Women with and without PCOS were genotyped for CYP3A7*1C, and this variant was tested for association with DHEAS and total and free testosterone.

SETTING:

Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham; controls were recruited from the surrounding community. Genotyping took place at Cedars-Sinai Medical Center (Los Angeles, CA).

PARTICIPANTS:

A total of 287 white women with PCOS and 187 controls were studied.

MAIN MEASUREMENTS:

CYP3A7*1C genotype, PCOS risk, and androgen levels were measured.

RESULTS:

PCOS subjects who carried the CYP3A7*1C variant had lower levels of serum DHEAS and total testosterone (P = 0.0006 and 0.046, respectively). The variant was not associated with PCOS risk.

CONCLUSION:

This study replicated prior work of the association of CYP3A7*1C and decreased DHEAS in a different population of young PCOS women, providing further genetic evidence that CYP3A7 plays a potential role in modulation of DHEAS levels. Adult expression of CYP3A7 may modify the PCOS phenotype by ameliorating adrenal androgen excess.

PMID:
18445661
[PubMed - indexed for MEDLINE]
PMCID:
PMC2453058
Free PMC Article
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