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Is the age of menopause determined in-utero?

OBJECTIVE: To determine whether age at menopause is related to size at birth. DESIGN: A follow-up study of two groups of women whose size at birth was recorded. SETTING: Hertfordshire and Sheffield, England. POPULATION: 755 women aged 60-71 years born in Hertfordshire; 235 women aged 40-42 years born in the Jessop Hospital, Sheffield. MAIN OUTCOME MEASURES: Age at natural menopause or serum follicle stimulating hormone concentration greater than 25 IU/ml. RESULTS: Age at menopause was unrelated to birth weight. However, it occurred at a younger age in women who had low weight at 1 year. This was independent of their body weight and smoking habits. In the population of younger women those who had had an early menopause tended to have been short at birth, with a high ponderal index (birth weight/length3). CONCLUSION: Growth retardation in late gestation, leading to shortness at birth and low weight gain in infancy, may be associated with a reduced number of primordial follicles in the ovary leading in turn to an earlier menopause.

Adult↗

Reproductive and general lifestyle determinants of age at menopause.

Determinants of age at menopause were evaluated using data of control subjects collected in the framework of a case-control study on breast and female genital tract neoplasms. After exclusion of women with surgical or pharmacological menopause, a total of 863 post-menopausal women aged 55-74 years admitted to a network of general and university hospitals for non-neoplastic, non-gynecological, non-endocrine-related acute conditions were considered for this analysis. No relationship emerged between cohort of birth, marital status and mean age at menopause. No association was observed with education, but women with 12 years of schooling or more reported a slightly later mean age at menopause (50.2 years vs. 49.3 for < 7 years of schooling). There was a strong, statistically significant association with smoking, mean age at menopause being more than 1 year earlier in ever-smokers than in never-smokers. Nulliparous women tended to report an earlier age at menopause (49.0 years) than parous ones (49.5) and mean age at menopause rose with number of births, being 49.8 in women reporting three or more births. This trend was of borderline statistical significance. No association emerged between age at menopause and number of spontaneous abortions, lifelong menstrual pattern and age at menopause. The significant association between smoking, parity and age at menopause observed in the univariate analysis was confirmed after taking into account the potential confounding effects of age and education in multivariate analysis.

Age Factors↗

Environment, human reproduction, menopause, and andropause.

As the hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator is an integrator of hormonal, metabolic, and neural signals, it is not surprising that the function of the hypothalamogonadal axis is subject to the influence of a large array of environmental factors. Before puberty, the central nervous system (CNS) restrains the GnRH pulse generator. Undernutrition, low socioeconomic status, stress, and emotional deprivation, all delay puberty. During reproductive life, among peripheral factors that effect the reproductive system, stress plays an important role. Stress, via the release of corticotropin-releasing factor (CRF), eventually triggered by interleukin 1, inhibits GnRH release, resulting in hypogonadism. Effects of CRF are probably mediated by the opioid system. Food restriction and underweight (anorexia nervosa), obesity, smoking, and alcohol all have negative effects on the GnRH pulse generator and gonadal function. Age and diet are important determinants of fertility in both men and women. The age-associated decrease in fertility in women has as a major determinant chromosomal abnormalities of the oocyte, with uterine factors playing a subsidiary role. Age at menopause, determined by ovarian oocyte depletion, is influenced by occupation, age at menarche, parity, age at last pregnancy, altitude, smoking, and use of oral contraceptives. Smoking, however, appears to be the major determinant. Premature menopause is most frequently attributable to mosaicism for Turner Syndrome, mumps ovaritis, and, above all, total hysterectomy, which has a prevalence of about 12-15% in women 50 years old. Premature ovarian failure with presence of immature follicles is most frequently caused by autoimmune diseases or is the consequence of irradiation or chemotherapy with alkylating cytostatics. Plasma estrogens have a physiological role in the prevention of osteoporosis. Obese women have osteoporosis less frequently than women who are not overweight. Early menopause, suppression of adrenal function (corticoids), and thyroid hormone treatment all increase the frequency of osteoporosis. Aging in men is accompanied by decreased Leydig cell and Sertoli cell function, which has a predominantly primary testicular origin, although changes also occur at the hypothalamopituitary level. Plasma testosterone levels, sperm production, and sperm quality decrease, but fertility, although declining, is preserved until senescence. Stress and disease states accelerate the decline on Leydig cell function. Many occupational noxious agents have a negative effect on fertility.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

Age at natural menopause in a population-based screening cohort: the role of menarche, fecundity, and lifestyle factors.

OBJECTIVE: To verify whether a population-based hypothesis (age at menarche and age at natural menopause have an inverse relationship) also applies at the level of the individual and to investigate what other factors predict age at natural menopause. DESIGN: Prospective cohort study (the Doorlopend Onderzoek Morbiditeit/Mortaliteit [DOM] project). SETTING: Prevention Breast Cancer Screening Centre, Utrecht, The Netherlands. PATIENT(S): A cohort of 3,756 Dutch women, born between 1911 and 1925, participating in a population-based breast cancer screening program, who experienced a natural menopause. Three samples of women were studied: a sample who did not use oral contraceptives (OCs) (n = 3,347), a sample of OC users (n = 409), and a combined sample of OC users and nonusers (n = 3,756). MAIN OUTCOME MEASURE(S): Age at menopause and menarche, fertility patterns, OC use, height, weight, smoking, and demographic variables. RESULT(S): No relation was found between age at menarche and age at natural menopause. The total percentage of variance in age at natural menopause explained by multiple regression including all factors was minimal, ranging from 1.3% to 9.7% in OC users. Linear regression analysis indicated a slight secular trend in age at menopause. CONCLUSION(S): Frisch's hypothesis could not be corroborated at the individual level. These results suggest that age at menarche and menopause should be treated as independent risk factors for breast cancer. Modification of age at menopause by lifestyle factors (except possibly for OC use) appears minimal.

Age Factors↗