Alterations in the Menstrual Cycle as a Peculiar Sign of Type 1 Diabetes Mellitus: A Meta-analytic Approach.

BACKGROUND: Menstrual irregularities are present in >30% of women with type 1 diabetes mellitus (T1DM). These abnormalities will likely lead to reduced fertility and earlier menopause. T1DM management has changed over time, with even more emphasis on stringent levels of glycemic management. Thus, we investigated whether therapeutic T1DM changes have an influence on the proportion of menstrual disorders in women with T1DM. METHODS: A meta-analysis was performed that included clinical trials in which menstrual abnormalities in women with T1DM were studied. The literature was checked for studies in which women with T1DM were compared with healthy, age-matched controls. Case-control, cohort, and cross-sectional studies were included. The primary endpoint was rate of menstrual dysfunction. RESULTS: Menstrual dysfunction was higher in women with T1DM compared with controls (odds ratio 2.08, 95% confidence interval [CI] 1.43 to 3.03, p<0.001), even when sensitivity analysis was performed, considering only studies published after 2000. The age at menarche was higher for women with T1DM compared with controls (mean difference 0.53, 95% CI 0.32 to 0.74 years, p<0.001). The proportion of menstrual abnormalities in T1DM was inversely related to diabetes duration, but was unrelated to both body mass index and glycated hemoglobin. CONCLUSIONS: The meta-analytic approach used confirmed the correlation between T1DM and menstrual irregularities. T1DM menstrual dysfunction seemed unrelated to change in therapeutic management across years, as well as to glycemic management and body weight. The underlying pathogenetic mechanisms are not fully understood.

Randomized double-blind placebo-controlled trial on levothyroxine and liothyronine combination therapy in totally thyroidectomized subjects: the LEVOLIO study.

OBJECTIVE: Despite having normal thyroid-stimulating hormone levels, many hypothyroid patients are dissatisfied with the treatment. The primary aim of this study was to evaluate the effect of twice-daily, combination therapy with levothyroxine (LT4) and liothyronine (LT3), at doses adapted according to TSH-level, on peripheral tissues as reflected by sex hormone binding globulin (SHBG) levels in totally thyroidectomized patients. Changes in other tissue markers and quality of life considering DIO2-rs225014 and MCT10-rs17606253 genetic variants were also assessed. DESIGN: Double-blind, randomized, placebo-controlled. METHODS: One hundred and forty-one subjects were randomized to LT4 + LT3 group (LT4 + LT3 in the morning and LT3 in the evening; n = 70) or placebo group (LT4 in the morning and placebo in the evening; n = 71). Pituitary-thyroid axis compensation was assessed after 6, 12, and 24 weeks. Clinical parameters, quality of life, and tissue markers (sex hormone binding globulin, serum lipids, bone markers) were evaluated at 12 and 24 weeks. DIO2 and MCT10 single nucleotide polymorphisms were genotyped. RESULTS: The LT4 + LT3 group was treated with mean daily LT3 doses of 5.00 µg, with a mean daily LT4 reduction of 15 µg. After 6 months of treatment, neither SHBG and other tissue markers nor quality of life differed significantly between groups. Combination treatment required greater dose adjustments than placebo (25% vs 54%, P < .001), due to thyroid-stimulating hormone reduction, without hyperthyroidism signs or symptoms. At the end of treatment, the LT4 + placebo group had significantly lower fT3/fT4 compared to the LT4 + LT3 group (0.26 ± 0.05 vs 0.32 ± 0.08, P < .001). No preference for combination therapy was found. Genetic variants did not influence any outcomes. CONCLUSIONS: Six months of combination therapy with twice-daily LT3 dose adapted according to TSH-level do not significantly change peripheral tissue response or quality of life, despite an increase in the fT3/fT4 ratio.