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Women with type 1 diabetes have a delayed menarche and a greater prevalence of menstrual disorders than women without diabetes. However, little is known about the menopause transition among type 1 diabetic women. The Familial Autoimmune and Diabetes (FAD) Study recruited both adult individuals who were identified from the Children's Hospital of Pittsburgh Type 1 Diabetes Registry for the years 1950 -1964 and their family members. Unrelated nondiabetic control probands and their relatives were also evaluated. Women with type 1 diabetes (n ‫؍‬ 143) compared with nondiabetic sisters (n ‫؍‬ 186) or unrelated control subjects (n ‫؍‬ 160) were more likely to have an older age at menarche (13.5, 12.5, and 12.6 years, respectively, P < 0.001), more menstrual irregularities before 30 years of age (45.7, 33.3, and 33.1%, respectively, P ‫؍‬ 0.04), and a younger age at menopause (41.6, 49.9, and 48.0 years, respectively, P ‫؍‬ 0.05). This resulted in a 6-year reduction in the number of reproductive years (30.0, 37.0, and 35.2 years, respectively, P ‫؍‬ 0.05) for women with type 1 diabetes. Risk factors univariately associated with earlier menopause included type 1 diabetes (hazard ratio [HR] 1.99, P ‫؍‬ 0.04), menstrual irregularities before 30 years of age (HR 1.87, P ‫؍‬ 0.04), nulliparity (HR 2.14, P ‫؍‬ 0.01), and unilateral oophorectomy (HR 6.51, P < 0.0001). Multivariate analysis confirmed that type 1 diabetes (HR 1.98, P ‫؍‬ 0.056), menstrual irregularities by 30 years of age (HR 2.36, P ‫؍‬ 0.01), and unilateral oophorectomy (HR 9.76, P < 0.0001) were independent determinants of earlier menopause in our cohort. We hypothesize that an earlier menopause, which resulted in a 17% decrease in reproductive years, is a major unstudied complication of type 1 diabetes.

OBJECTIVE -To evaluate menstrual cycle histories among women with type 1 diabetes, their sisters, and unrelated control subjects without diabetes across all reproductive ages.RESEARCH DESIGN AND METHODS -Menstrual and reproductive histories were obtained by questionnaire from 143 women with type 1 diabetes, 186 sisters without diabetes, and 158 unrelated control subjects without diabetes participating in the Familial Autoimmune and Diabetes study.RESULTS -Women with type 1 diabetes had more menstrual problems (long cycles, long menstruation, and heavy menstruation) before age 30 years than sisters and control subjects. These differences were all statistically significant, except for heavy menstruation at age Ͻ20 years. No differences were observed after age 30 years. Women with type 1 diabetes experienced later menarche, earlier natural menopause, fewer pregnancies, and more stillbirths than women without diabetes. Multiple regression analyses revealed that type 1 diabetes caused an approximate twofold increased risk of any menstrual problem before age 30 years. These were primarily related to long cycles and long menstruation in women aged Ͻ20 and 20 -29 years, as well as with heavy menstruation from 20 to 29 years. Oral contraceptives were protective for any menstrual problem and heavy menstruation from 30 to 39 years of age. With history of pregnancy from 20 to 40 years of age, any menstrual problem and long menstruation were more likely.CONCLUSIONS -The results suggest that type 1 diabetes is an independent risk factor for menstrual disturbances in young adults. Future studies may determine whether addressing menstrual disturbances improves quality of life and health for these women.

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Thyroid hormones play major roles in the regulation of a wide range of metabolic and physiologic processes, but the genes and environmental factors that affect normal, quantitative variation in thyroid hormone concentrations are largely unknown. Using quantitative genetic methods, we evaluated the effects of genes and environmental factors on thyroid hormone variation in 586 women and 425 men from 27 randomly ascertained Mexican-American families from the San Antonio Family Heart Study. Data were available on free and total T(4), free and total T(3), TSH, thyroglobulin, and T(4)-binding globulin, as well as on covariates, including sex, age, weight, lifestyle habits, physical activity, and others. These covariates accounted for 2-18% of total phenotypic variation, whereas genes accounted for 26-64% of the variation. Overall, free T(3) had the highest heritability, which is noteworthy because it is the most biologically active thyroid hormone and accounts for the vast majority of metabolic and physiologic effects of thyroid hormones. Our results indicate that genes account for a substantial portion of variation in human thyroid hormone levels, and suggest that further studies to identify the genes involved in this variation could reveal important insights into the processes that govern thyroid-mediated metabolism.

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