Possible molecular mechanisms to explain the non-linear repeat size risk for ovarian insufficiency are discussed.

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PURPOSE Common polymorphisms in the N-acetyltransferase-2 (NAT2) metabolic enzyme determine slow or rapid acetylator phenotypes. We investigated the effects of alcohol, smoking, and caffeine on fecundability, and determined whether the effects were modified by NAT2. METHODS Three NAT2 polymorphisms were genotyped in 319 women office workers participating in a prospective pregnancy study (1990–1994). Women were ages 20–41 and at risk for pregnancy. Discrete-time survival analysis was used to determine the effects of alcohol, smoking, and caffeine on fecundability and evaluate effect modification by NAT2. RESULTS 319 women (161 slow acetylators, 158 rapid) were followed for an average of 8 menstrual cycles, resulting in 124 pregnancies. There was no effect of caffeine on fecundability. Drinking 1+ alcoholic drink/day and current smoking were significantly associated with reduced fecundability, but only among slow acetylators (adjusted fecundability odds ratio (FOR) for smoking= 0.34: 95% CI, 0.22, 0.90; adjusted FOR for 1+ drink/day = 0.20: 0.05, 0.92). There was no effect among rapid acetylators. CONCLUSIONS NAT2 status significantly modified the effects of alcohol and smoking on fecundability, emphasizing the importance of incorporating genetic and metabolic information in studies of reproductive health. Replication of this study is warranted.

BackgroundThe upward trend in industrial nations in the incidence of male genitourinary (GU) conditions may be attributed to increased exposure to endocrine disruptors. Polybrominated biphenyl (PBB), a brominated flame retardant, is one such suspected endocrine disruptor.ObjectiveWe investigated the relationship between maternal serum levels of PBBs and GU conditions among male offspring exposed in utero.MethodsIn this cohort study of sons born to women accidentally exposed to PBBs during 1973–1974, we examined self-reported data on GU conditions among male offspring in relation to maternal serum PBB levels. We used generalized estimating equations to calculate odds ratios (ORs), controlling for gestational age at birth.ResultsOf 464 sons, 33 reported any GU condition (13 hernias, 10 hydroceles, 9 cryptorchidism, 5 hypospadias, and 1 varicocele). Four reported both hernia and hydrocele, and one both hernia and cryptorchidism. After adjustment for gestational age at birth, sons of highly exposed women (> 5 ppb) were twice as likely to report any GU condition compared with sons of the least exposed women [≤1 ppb; OR = 2.0; 95% confidence interval (CI), 0.8–5.1]. This risk was increased when we excluded sons born after the exposure but before the mother’s serum PBB measurement (OR = 3.1; 95% CI, 1.0–9.1). We found evidence of a 3-fold increase in reported hernia or hydrocele among sons with higher PBB exposure (test of trend p-value = 0.04). Neither hypospadias nor cryptorchidism was individually associated with PBB exposure.ConclusionsAlthough cryptorchidism and hypospadias were not associated with in utero PBB exposure, this study suggests that other GU conditions may be associated with exposure to endocrine-disrupting chemicals during development.

Purpose-We examined the association between endometriosis and exposure to polybrominated biphenyls (PBBs) and polychlorinated biphenyls (PCBs) among women inadvertently exposed to PBBs in 1973.Methods-Serum PBB and PCB were measured in the late 1970s. Women self-reported endometriosis at interview in 1997. We constructed Cox models to estimate the relative incidence of endometriosis in relation to PBB and PCB levels.Results-Seventy-nine of 943 women (9%) reported endometriosis. Compared to women with low PBB exposure (≤ 1 parts per billion [ppb]), women with moderate PBB (1-4 ppb) (hazard ratio [HR] = 0.72; 95% confidence interval [CI], 0.39-1.31) and high PBB (≥ 4 ppb) (HR = 0.90; 95% CI, 0.51-1.59) exposure did not have increased incidence of endometriosis. Increased incidence of endometriosis was suggested among women exposed to moderate PCB (5-8 ppb) (HR = 1.67; 95% CI, 0.91-3.10) and high PCB (≥ 8 ppb) (HR = 1.68; 95% CI, 0.95-2.98) levels compared to low PCB exposure (≤ 5 ppb).Conclusions-Our study does not support an association between PBB exposure and endometriosis. Findings for serum PCB level are consistent with an emerging body of literature suggesting an association between PCB exposure and endometriosis.