Age of menarche and time to pregnancy.

STUDY QUESTION: Is age of menarche (AOM) associated with subfecundity and/or infertility in adulthood? STUDY ANSWER: A late onset of menarche was associated with a slightly increased risk of subfecundity and infertility. WHAT IS KNOWN ALREADY: Abnormal age at onset of menarche is a risk factor for several diseases later in life, but the effect on infertility is unknown. STUDY DESIGN, SIZE AND DURATION: A cohort study of  73 107 pregnant Danish women enrolled in the Danish National Birth Cohort (DNBC) between 1996 and 2002 with self-reported data on AOM and waiting time to pregnancy (TTP). PARTICIPANTS/MATERIALS, SETTING AND METHODS: Information on AOM and TTP was collected through a computer-assisted telephone interview scheduled in pregnancy Week 12. We estimated adjusted odds ratios (ORs) with 95% confidence intervals (CIs) using multivariate logistic regression with TTP categorized as subfecundity (TTP ≥6 months) and infertility (TTP >12 months). Multiple imputation was performed to account for missing data. MAIN RESULTS AND THE ROLE OF CHANCE: We found trends towards higher odds of subfecundity and infertility with increasing age of menarche, using 13 years as the starting point. Among women reaching menarche at 15 years, the odds for subfecundity were 1.09 (95% CI: 1.03-1.15), and 1.17 (95% CI: 1.09-1.25) for women reaching menarche later than 15 years compared with the reference group of girls reaching menarche at 13 years. Additionally, women reaching menarche older than 15 years had an OR of infertility of 1.18 (95% CI: 1.08-1.29). Women younger than 11 years at menarche had lower odds of subfecundity. The results were generally attenuated when adjusting for women's age of pregnancy, but the significant positive trend of higher OR for subfecundity persisted, as did the higher OR for subfecundity among women experiencing menarche older than 15 years. LIMITATIONS, REASONS FOR CAUTION: We used retrospectively collected self-reported information on AOM and TTP. Information on male factors was limited in this cohort. We only included pregnant women and have therefore no data on women with untreated and unsuccessfully treated infertility, limiting the generalizability to women who became pregnant. WIDER IMPLICATION OF THE FINDINGS: This study indicates that the onset of menarche at 15 years or later is associated with subfecundity and infertility. STUDY FUNDING/COMPETING INTERESTS: The Danish National Research Foundation has established the Danish Epidemiology Science Centre that initiated and created the DNBC. The cohort is furthermore a result of a major grant from this Foundation. Additional support for the DNBC is obtained from the Pharmacy Foundation, the Egmont Foundation, the March of Dimes Birth Defects Foundation, the Augustinus Foundation and the Health Foundation. This specific study was supported by a scholarship from the Ministry of Science and Innovation. No conflict of interest declared.

Maternal pre-pregnancy body mass index and pubertal development among sons.

Maternal overweight and obesity in pregnancy has been associated with earlier age of menarche in daughters as well as reduced semen quality in sons. We aimed at investigating pubertal development in sons born by mothers with a high body mass index (BMI). The study included 2522 sons of mothers that during pregnancy in 1984-1987 were enrolled in a mother-child cohort and gave information on their pre-pregnancy height and weight from which we calculated their BMI. Information on sons' pubertal development, assessed by age when starting regular shaving, voice break, acne and first nocturnal emission, was obtained from web-based questionnaires in 2005, when sons were 18-21 years old. Multiple linear regression analyses showed that sons of obese mothers on average started to shave regularly 8.3 (95% confidence interval: 2.5-14.0) months earlier than sons of normal weight mothers. For the three other indicators of pubertal development, results also indicated earlier pubertal development among sons of obese mothers. After excluding sons of underweight mothers in a subanalysis, we observed an inverse trend between maternal pre-pregnancy BMI and age at regular shaving, acne and first nocturnal emission. In conclusion, maternal pre-pregnant obesity may be related to earlier timing of pubertal milestones among sons. More research, preferably based on prospectively collected information about pubertal development, is needed to draw firm conclusions.

Maternal cigarette smoking during pregnancy and pubertal development in sons. A follow-up study of a birth cohort.

Epidemiological studies have raised concern about the reproductive consequences of prenatal cigarette smoking exposure, possibly affecting semen quality and onset of pubertal development of the offspring. The aim of this study was to further investigate pubertal development in young men exposed to cigarette smoking in foetal life. In a Danish pregnancy cohort, information on maternal smoking during pregnancy was available from questionnaires administered in 1984-1987, and information on pubertal development, assessed by age at first nocturnal emission, acne, voice break and regular shaving, was obtained from a follow-up questionnaire administered in 2005 to the young men (age: 18-21). We found no significant association between prenatal cigarette smoking exposure and earlier onset of puberty, but we did observe a tendency towards earlier age of first nocturnal emission, acne and voice break, indicating an accelerated age of pubertal development. Men exposed to ≥15 cigarettes/day had 3.1 months (95% CI: -6.4; 0.2) earlier age at acne and 2.2 months (95% CI: -7.3; 3.0) earlier age at first nocturnal emission, 1.2 months (95% CI: -4.6; 2.2) earlier age at voice break, however, 1.3 months (95% CI: -1.6; 4.3) later age at regular shaving, compared with unexposed men. Prenatal cigarette smoking exposure may induce an earlier age at onset of puberty in young men, but larger studies with prospectively collected data on pubertal development are needed to explore this hypothesis further.

Maternal smoking during pregnancy and reproductive health of daughters: a follow-up study spanning two decades.

STUDY QUESTION: Does in utero exposure to constituents of cigarette smoke have a programming effect on daughters' age of menarche and markers of long-term reproductive health? SUMMARY ANSWER: In utero exposure to constituents of cigarette smoke was associated with earlier age of menarche and--to a lesser extent--changes in the testosterone profile of the young women. WHAT IS KNOWN ALREADY: Studies observe potential effects of in utero exposure to constituents of cigarette smoke on the intrauterine formation of female gonads, but the consequences on long-term reproductive health in daughters remain unclear. STUDY DESIGN, SIZE AND DURATION: A prospective cohort study was designed using data from 965 pregnant women enrolled prior to a routine 30th-week antenatal examination at a midwifery practice in Denmark from 1988 to 1989 and a follow-up of their 19-21-year-old daughters in 2008. PARTICIPANTS/MATERIALS, SETTING AND METHODS: The pregnant women provided information on lifestyle factors during pregnancy, including the exact number of cigarettes smoked per day during the first and the second trimesters. A total of 438 eligible daughters were asked to complete a web-based questionnaire on reproductive health and subsequently invited to participate in a clinical examination during 2008. Of the 367 daughters (84%) who answered the questionnaire, 267 (61%) agreed to further examination. Information on menstrual pattern was provided at examination, blood samples were drawn to be analyzed for serum levels of reproductive hormones [FSH, LH, estradiol (E(2)), sex hormone-binding globulin, anti-Müllerian hormone, dehydroepiandrosterone-sulphate (DHEAS), free testosterone and free E(2)] and number of follicles (2-9 mm) were examined by transvaginal ultrasound. The daughters were divided into three exposure groups according to the level of maternal smoking during first trimester [non-exposed (reference), low-exposed (mother smoking >0-9 cigarettes/day) and high-exposed (mother smoking ≥ 10 cigarettes/day)]. Data were analyzed by multiple regression analyses in which we adjusted for potential confounders. Both crude and adjusted test for trend were carried out using maternal smoking during the first trimester as a continuous variable. MAIN RESULTS AND THE ROLE OF CHANCE: We observed an inverse association between in utero exposure to constituents of cigarette smoke and age of menarche (P = 0.001). Daughters exposed to >0-9 cigarettes/day debuted with -2.7 [95% confidence interval (CI) -5.2 to -0.1] percentage earlier age of menarche, whereas daughters exposed to ≥ 10 cigarettes/day had -4.1 (95% CI: -6.6 to -1.5) percentage earlier age of menarche corresponding to 6.5 (95% CI: -10.7 to -2.2) months. There was a non-significant tendency towards lower levels of testosterone and DHEAS with increasing in utero exposure to constituents of cigarette smoke but no associations with follicle number, cycle length or serum levels of the other reproductive hormones were observed. LIMITATIONS AND REASONS FOR CAUTION: We collected information on age of menarche retrospectively but the recall time was relatively short (2-10 years) and the reported values were within the normal range of Caucasians. Analyses of reproductive hormones are presented only for the group of daughters who were non-users of hormonal contraceptives because users were excluded, leaving only a low number of daughters available for the analyses (n = 75), as reflected in the wide CIs. The analyses of hormones were further adjusted for menstrual phase at time of clinical examination (follicular, ovulation and luteal phase) because blood samples were not collected on a specific day of the menstrual cycle. WIDER IMPLICATIONS OF THE FINDINGS: This study supports the limited evidence of an inverse association between maternal smoking during pregnancy and age of menarche and further addresses to what extent reproductive capacity and hormones may be programmed by maternal smoking during pregnancy. A trend toward earlier maturation of females is suggested to have implications on long-term reproductive function. STUDY FUNDING/COMPETING INTEREST(S): Supported by a scholarship from The Lundbeck Foundation (R93-A8476). No conflict of interest declared.

Does last week's alcohol intake affect semen quality or reproductive hormones? A cross-sectional study among healthy young Danish men.

The association between last 5 days of alcohol intake, semen quality and reproductive hormones was estimated in this cross-sectional study among 347 men. Conventional semen characteristics, DNA fragmentation index and reproductive hormones (testosterone, estradiol, sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and inhibin B) were determined. There was a tendency towards lower semen characteristics at higher intake of alcohol past 5 days, albeit with no statistically significant dose-response association. The ratio between free estradiol and free testosterone was higher at higher alcohol intake during the 5 days preceding semen sampling. In conclusion, alcohol intake was associated with impairment of most semen characteristics but without a coherent dose-response pattern. The study indicates an association between recent alcohol intake and a hormonal shift towards higher estradiol/testosterone ratio. The hormonal changes observed may over time, lead to adverse effects on semen quality, but longitudinal studies are needed to study this.

Exposures that may affect sperm DNA integrity: two decades of follow-up in a pregnancy cohort.

Prenatal lifestyle exposures are linked to alterations in conventional semen characteristics. Sperm DNA integrity is another marker of semen quality shown to be altered in mice prenatally exposed to chemicals. From a Danish pregnancy cohort established in 1984-1987, sons were selected for a follow-up study in 2005-2006. We examined associations between prenatal and current lifestyle exposures and DNA fragmentation index (DFI) among 337 men. Sons of overweight mothers had 22% (95% CI: -3; 52) higher DFI than sons of normal weight mothers and sons of parents with a TTP >12 months had 14% (95% CI: -4; 34) higher DFI than sons of parents with a TTP of 0-6 months. Abstinence time was positively associated with DFI (p<0.005). Overweight men had higher DFI compared to normal weight men, however, statistically insignificantly. In conclusion, results indicate that DFI is affected by prenatal exposures, but confidence limits are wide and results statistically insignificant.