Early T1D Onset Linked With Shorter Reproductive Periods Among Women

An analysis of data from participants in the Pittsburgh Epidemiology of Diabetes Complications (EDC) study and the Study of Women’s Health Across the Nation (SWAN) show women with type 1 diabetes (T1D) onset before menarche experience a shorter reproductive period compared with controls. Findings were published in Menopause, the journal of The North American Menopause Society (NAMS).

Previous research suggests insulin deficiency and hyperglycemia may disrupt the female reproductive system’s normal function, the authors explained. This could lead to delayed menarche in women with T1D and premature ovarian aging.

Through its effects on gonadotropin-releasing hormone neurons in the central nervous system, and the granulosa, thecal, and stromal components in the ovarian system, insulin plays an important role in regulating female reproductive function.

Although studies have investigated the impacts of insulin deficiency on onset of menarche, evidence regarding the effect of T1D on age of natural menopause is limited and conflicting.

To address this knowledge gap, the researchers assessed the length of reproductive years among women with T1D in the EDC study (n = 105) and those without diabetes from SWAN (n = 178).

“Since EDC participants were younger at study entry compared with participants of the SWAN cohort, covariate data for women with T1D were taken from the follow-up visit preceding menopause in which chronological age was closest to the mean baseline age (46 years) in SWAN,” the researchers explained. This time point was considered the baseline for the current analysis.

To determine length of reproductive years, the investigators subtracted the age at menarche from the age at natural menopause. Women who received a hysterectomy/oophorectomy before menopause or sex hormone therapy during the menopausal transition were excluded from the study.

Women in the T1D cohort were younger than those without T1D (mean [SD] age, 42.8 [7.3] vs 46 [2.4] years; P = .002). Mean diabetes duration in this cohort was 33.5 (8) years, with a mean age of diabetes onset at 9.3 (3.9) years. In addition, 96.2% of women with T1D in the EDC study were non-Hispanic White and 3.8% were Black, while 67.4% of those in SWAN were non-Hispanic White and 32.6% were Black.

Patients with T1D were also less likely to smoke, and they exhibited lower body mass index, diastolic blood pressure, total cholesterol, and triglyceride concentrations, but had higher high-density lipoprotein cholesterol levels compared with controls.

Adjusted analyses revealed:

• Women with T1D were older at menarche (0.5-year delay; P = .002) but younger at natural menopause (−2 years; P <.0001)
• Women with T1D experienced 2.5 fewer reproductive years compared with those without T1D (P <.0001)
• Findings were restricted to the subgroup of women whose T1D was diagnosed before reaching menarche (n = 80)

The age at menarche did not significantly differ between women with T1D whose diabetes onset occurred after menarche (12.2 [1.2] years; n = 25) and SWAN study participants (P = .20)

Women with T1D were less likely to have ever used oral contraceptives and to have been pregnant, while among those who had at least 1 pregnancy, the mean number of pregnancies and mean number of live births were lower in this cohort.

Researchers also found women with T1D had 3.4 years shorter unadjusted length of reproductive period compared with controls, regardless of whether T1D onset preceded or followed menarche.

Overall, findings showed women with T1D “are not only at risk for premature ovarian aging because of early onset T1D, they are also at increased risk for cardiovascular disease, osteoporosis, and early mortality because of early natural menopause,” said Stephanie Faubion, MD, MBA, the medical director at NAMS.

“Understanding these risks and targeting appropriate risk-reducing strategies are key to optimizing the health and quality of life of these women," she added.

Authors hypothesized a possible mechanism underlying the observed shortened length of reproductive years may involve the disruption of the hypothalamic-pituitary-ovarian axis function and premature ovarian aging caused, in part, by hyperglycemia.

It is possible that age difference between the cohorts at analytic baseline, despite being adjusted for in analyses, may have resulted in residual confounding and affected study findings, marking a limitation.

“Given the high likelihood of experiencing early menopause in T1D, and the enormous impact on health associated with early menopause, further studies are needed to determine modifiable factors that contribute to early menopause to improve reproductive health in women with T1D,” the researchers concluded.

Reference

Yi Y, Khoudary SRE, Buchanich JM, et al. Women with type 1 diabetes experience shorted reproductive period compared with nondiabetic women: the Pittsburgh epidemiology of diabetes complications (EDC) study and the study of women’s health across the nation (SWAN). Menopause. Published online March 1, 2021. doi:10.1097/GME.0000000000001758