Heritability of dehydroepiandrosterone sulfate in women with polycystic ovary syndrome and their sisters

Fertil Steril. 2006 Dec;86(6):1688-93. doi: 10.1016/j.fertnstert.2006.05.045. Epub 2006 Oct 30.


Objective: To test the hypothesis that adrenal androgen (AA) secretion is an inherited trait in PCOS and that serum DHEAS concentrations, as a marker of AA secretion, will be correlated between women with PCOS and their sisters.

Design: Prospective case-control.

Setting: Tertiary care center.

Patient(s): Sixty-two PCOS probands and 69 sisters.

Intervention(s): None.

Main outcome measure(s): The DHEAS concentrations and clinical phenotypes were obtained. Familial correlation between sisters was estimated. A variance components model was used to estimate the heritability (h(2)) of the DHEAS levels. Body mass index (BMI)-adjusted DHEAS levels were used in all of the analyses.

Result(s): There was no difference in age between the proband and sister groups (28.7 +/- 8.1 years vs. 28.0 +/- 8.8 years, P=.65), and probands had higher BMI values (33.4 +/- 7.6 kg/m(2) vs. 27.9 +/- 7.0 kg/m(2), P<.001). Sixteen of the 69 (23.2%) sisters were affected by PCOS. The sister-sister correlation of DHEAS level was 0.28 +/- 0.12 for the whole group (P<.05), and this correlation was higher, at 0.38 +/- 0.14 (P< or =.05), after excluding 31% of the affected sisters and 34% of the unaffected sisters who received hormonal therapy at or within 3 months of the time of the study. The h(2) estimates of DHEAS were 0.43 (P=.037) and 0.44 (P=.062) when all sisters and only untreated sisters, respectively, were included in the analysis.

Conclusion(s): The correlation of serum DHEAS levels between PCOS probands and their sisters suggests a familial component in the regulation of DHEAS levels and possibly AA production in PCOS. The h(2) estimates of 0.43-0.44 for BMI-adjusted DHEAS suggest that genetic factors account for between 40% and 50% of the overall variation in DHEAS levels in these women. Our results support the hypothesis that circulating AA levels represent an inherited trait in PCOS.

Publication types

  • Controlled Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Androgens / blood*
  • Biomarkers / blood
  • Dehydroepiandrosterone / blood*
  • Female
  • Humans
  • Polycystic Ovary Syndrome / blood*
  • Polycystic Ovary Syndrome / congenital
  • Polycystic Ovary Syndrome / genetics*
  • Siblings*


  • Androgens
  • Biomarkers
  • Dehydroepiandrosterone