Maternal polycystic ovarian syndrome and pubertal development in daughters and sons: a population-based cohort study
Authors: Lunddorf Lea Lykke Harrits , Arendt Linn Håkonsen , Ernst Andreas , Brix Nis , Knudsen Ulla Brent , Olsen Jørn , Ramlau-Hansen Cecilia Høst 
Published: September 2022

Abstract

STUDY QUESTION
Does maternal polycystic ovarian syndrome (PCOS) affect the timing of pubertal development in daughters and sons?

SUMMARY ANSWER
Maternal PCOS was associated with earlier adrenarche in daughters.

WHAT IS KNOWN ALREADY
Female adolescents with PCOS often experience earlier adrenarche compared to adolescents without PCOS, due to hyperandrogenism. Likewise, they usually have hyperandrogenism during pregnancy, which might potentially affect the development of the foetus, including its future reproductive health.

STUDY DESIGN, SIZE, DURATION
In this population-based cohort study, we included 15 596 mothers–child pairs from the Danish National Birth Cohort (DNBC) Puberty Cohort, who were followed from foetal life until full sexual maturation or 18 years of age.

PARTICIPANTS/MATERIALS, SETTING, METHODS
Using register-based and self-reported information on maternal PCOS and menstrual irregularities, collected during pregnancy, we categorized the mothers as having PCOS (n = 251), oligomenorhoea (n = 134), ‘other menstrual irregularities’ (n = 2411) or no menstrual abnormalities (reference group, n = 12 800). The children provided self-reported information on pubertal development every 6 months from the age of 11 years. The main outcome measures were adjusted mean age differences (in months) at attaining several individual pubertal milestones using an interval-censored regression model, as well as the average difference in age at attaining all pubertal milestones combined into a single estimate using Huber–White robust variance estimation.

MAIN RESULTS AND THE ROLE OF CHANCE
We found that maternal PCOS was associated with an accelerated pubertal development in daughters with an overall average difference of −3.3 (95% CI: −6.3; −0.4) months based on all pubertal milestones compared to the reference group. When further looking into the average difference for adrenarche only (pubarche, axillary hair and acne), the average difference was −5.4 (95% CI: −8.7; −2.1) months compared to the reference group; whereas thelarche and menarche did not occur earlier in daughters of mothers with PCOS (average difference: −0.8 (95% CI: −3.9; 2.4) months). Oligomenorrhoea and ‘other menstrual irregularities’ were not associated with pubertal development in daughters. Neither PCOS, oligomenorrhoea nor ‘other menstrual irregularities’ were associated with pubertal development in sons.

LIMITATIONS, REASONS FOR CAUTION
We expect some degree of non-differential misclassification of maternal PCOS and menstrual irregularities as well as pubertal development in the children.

WIDER IMPLICATIONS OF THE FINDINGS
Maternal PCOS might accelerate adrenarche in daughters. Whether this is due to genetics, epigenetics or prenatal programming by hyperandrogenism in foetal life remains unsolved. The results from the present study can be generalized to Caucasian populations.

STUDY FUNDING/COMPETING INTEREST(S)
The study is funded by the Faculty of Health at Aarhus University. The authors have no financial relationships or competing interests to disclose.

TRIAL REGISTRATION NUMBER
N/A.