Androgen levels in the fetal cord blood of children born to women with polycystic ovary syndrome: a meta-analysis

Abstract

Introduction Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in reproductive-aged women. It is reported that intrauterine exposure to hyperandrogenism may induce the development of PCOS and associated complications in later life. To analyze the intrauterine androgen levels in infants born to PCOS mothers, we evaluated the androgen levels in fetal cord blood through a meta-analysis of observational studies. Material and methods The following online databases were systematically searched: PubMed, EMBASE, Cochrane library databases and Web of Science up to December 2019. Human studies compared cord blood androgen levels, including testosterone (T) and androstenedione (ADION), in fetal cord blood of mothers with and without PCOS. Statistical analysis was performed in Review Manager, Version 5.3, with the inverse variance method based on a random-effects model. Results A total of 7 articles were scrutinized and a total of 570 samples including 268 female and 222 male infants were qualified for review. In the mass spectrograph (MS) subgroup, PCOS mothers showed no signs of increased T concentration in umbilical cord blood at birth (4 studies; hazard ratio [HR] = − 0.05; 95% confidence interval [CI] = [− 0.33,0.24]; I 2 = 7%; P = 0.75; fixed-effects model). ADION level tends to be lower in daughters’ cord blood of PCOS mothers (3 studies; HR = -0.59; 95%CI = [− 1.00, − 0.19]; I 2 = 0%; P = 0.004; fixed-effects model). Conclusions Fetal cord blood T level is not related to PCOS, while ADION levels tend to be lower in the cord blood of daughters born to mothers with PCOS.

Elevated Anti-Müllerian Hormone Levels in Newborns of Women with Polycystic Ovary Syndrome: a Systematic Review and Meta-analysis Based on Observational Studies

“…Although numerous animal studies laid the foundations of this developmental hypothesis for PCOS etiology [18,19], however, this theory was doubted in human for many years, and insufficient observational human studies were conducted with controversial results. The latest meta-analysis concluded that fetal cord blood testosterone and dehydroepiandrosterone (DHEA) levels were not related to PCOS, while the androstenedione (ADION) levels were tended to be reduced in newborns of PCOS mothers [20], which was opposite to the present hypothesis. It could be explained that maternal testosterone might be bound by sex hormone-binding globulin (SHBG) and then quickly degraded and converted by the placenta's high levels of aromatase into estradiol.…”

Endocrine and metabolic interactions in healthy pregnancies and hyperinsulinemic pregnancies affected by polycystic ovary syndrome, diabetes and obesity

“…The authors suggest that T may be quickly degraded and converted by placental aromatase into E2 when passing through the placenta. However, cord blood A4 levels in female newborns were significantly lower in PCOS than in the control group ( 125 ). As explained in section 2, cord blood androgens are derived from both fetal adrenal as well as placental steroidogenesis.…”

“…Levels of DHEA and DHEAS in fetal cord blood were generally not associated with PCOS ( 73 , 74 , 88 , 95 ), but studies regarding T and A4 have produced conflicting results. A recent meta-analysis of seven studies (n= 570) found no significant differences in cord blood T levels between women with and without PCOS, irrespective of neonatal sex ( 125 ). The authors suggest that T may be quickly degraded and converted by placental aromatase into E2 when passing through the placenta.…”

“…The fetal adrenals produce DHEAS in utero , which is transformed into A4, T, and E2 by the placenta ( 126 ). Alterations of steroidogenesis in the fetus or an abnormality in placental steroidogenesis could potentially account for the decreased A4 levels ( 125 ). Similarly, Kelly et al.…”

Effects of Backfat Thickness on Oxidative Stress and Inflammation of Placenta in Large White Pigs

“…The maternal conditions are demonstrated to be closely related to the endocrine function of sows and piglets [5]. Pregnant sows are characterized by a high level of oxidative stress, which further influences the endocrine function of the fetoplacental unit [6,7].…”