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Observational Study
. 2022 Feb 17;107(3):e912-e923.
doi: 10.1210/clinem/dgab812.

Profile of Daughters and Sisters of Women With Polycystic Ovary Syndrome: The Role of Proband's Glucose Tolerance

Soren Harnois-Leblanc  1   2 , Maria Isabel Hernandez  2 , Ethel Codner  3 , Fernando Cassorla  3 , Sharon E Oberfield  4 , Natasha I Leibel  4 , Revi P Mathew  5 , Svetlana Ten  6 , Denis A Magoffin  7 , Christianne J Lane  8 , Michael I Goran  9 , Ricardo Azziz  10   11 , Jean-Patrice Baillargeon  1   12 , David H Geller  9   13
Affiliations
Observational Study

Profile of Daughters and Sisters of Women With Polycystic Ovary Syndrome: The Role of Proband's Glucose Tolerance

Soren Harnois-Leblanc et al. J Clin Endocrinol Metab. .

Abstract

Context: First-degree relatives of women with polycystic ovary syndrome (PCOS) present hormonal and metabolic alterations compared to girls unrelated to PCOS. It is unknown whether glucose intolerance in the PCOS proband confers a more severe metabolic predisposition on their first-degree relatives.

Objective: To determine whether glucose tolerance status in women with PCOS is associated with worsened glucose metabolism and sex hormone levels in their peripubertal daughters or sisters.

Design: Cross-sectional study.

Setting: Seven academic centers in North America, South America, and Europe.

Patients: Sixty-four pairs of women with PCOS and their daughters or younger sisters aged between 8 and 14 years were recruited. Twenty-five mothers or older sisters with PCOS were glucose intolerant (GI) and 39 were normal glucose tolerant (NGT).

Main outcome measures: Beta-cell function estimated by the insulin secretion-sensitivity index-2 (ISSI-2) during an oral glucose tolerance test and by the disposition index during a frequently sampled IV glucose tolerance test. Free testosterone and 17-hydroxyprogesterone (17-OHP) levels.

Results: Being related to a GI PCOS proband was associated with a lower ISSI-2 (P-value = 0.032) after adjusting for ethnicity, body mass index z-score, and pubertal stage. They also had higher free testosterone (P-value = 0.011) and 17-OHP levels compared to girls with an NGT proband, the latter becoming significant after adjusting for confounders (P-value = 0.040).

Conclusions: Compared to first-degree female relatives of women with PCOS and NGT, first-degree relatives of women with PCOS and GI display lower beta-cell function and hyperandrogenemia, putting them at higher risk of GI and PCOS development.

Keywords: adolescent; first-degree relatives; glucose homeostasis; pediatric; polycystic ovary syndrome; sex hormones.

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Figures

Figure 1.
Figure 1.
Boxplots of glucose homeostasis indices, from the oral glucose tolerance test and the frequent sampling intravenous glucose tolerance test in daughters or younger sisters having a proband with normal glucose tolerance (dark grey) and in those having a proband with glucose intolerance (light grey), stratified by Tanner pubertal stages 1, 2, and 3-4-5. Abbreviations: AIRg, acute insulin response to glucose; CIR30, corrected insulin response at 30 min; FSIVGTT, frequently sampling IV glucose tolerance test; ISI, insulin sensitivity index; ISSI-2, insulin secretion-sensitivity index-2; OGTT, oral glucose tolerance test.
Figure 2.
Figure 2.
Box plots of total testosterone, free testosterone, DHEA, and 17-hydroxy-progresterone in daughters or younger sisters having a proband with normal glucose tolerance (dark grey) and in those having a proband with glucose intolerance (light grey), stratified by Tanner pubertal stages 1, 2, and 3-4-5. Abbreviations: DHEA: dehydroepiandrosterone.
See this image and copyright information in PMC

References

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