The Influence of Prepubertal Onset of Type 1 Diabetes and Age of Menarche on Polycystic Ovary Syndrome Diagnosis

Abstract

Context Higher prevalence of polycystic ovary syndrome (PCOS) in women with type 1 diabetes (T1DM) is linked to exogenous insulin, especially when diabetes is diagnosed before puberty. Objective The study evaluates the impact of prepubertal onset of T1DM and insulin therapy on PCOS diagnosis and phenotypic characteristics in women with T1DM. Design, Setting and Patients We studied 83 women with T1DM (age – 26±5 years, BMI – 24±3 kg/m 2) – 36 with premenarchal onset of T1DM (17 with PCOS diagnosed – PCOS+PM, 19 without PCOS – noPCOS+PM) and 47 with postmenarchal onset of T1DM (24 with PCOS – PCOS-noPM and 23 without PCOS – noPCOS-noPM). Outcome Measurements Clinical examination, assessment of serum sex hormones, glycated haemoglobin (HbA1c) and ultrasonographic evaluation of the ovaries were performed in all women. Results Applying Rotterdam criteria, 49% of women with T1DM were diagnosed with PCOS. There were no differences in hormonal profile and ovarian parameters between PCOS+PM and PCOS-noPM. Women with T1DM+PM had higher insulin dose/24h and U/kg bw/24h than T1DM-noPM (p=0.014; p=0.001, respectively). Both PCOS+PM and noPCOS+PM groups had higher insulin dose U/kg bw/24h in comparison to PCOS-noPM (p=0.004; p=0.006, respectively). In multivariable logistic regression analysis, age of menarche (OR: 0.672; 95% CI: 0.465-0.971) and HbA1c (OR: 0.569; 95% CI: 0.383-0.846) were associated with the diagnosis of PCOS. Conclusions There were no differences in the prevalence of PCOS between T1DM+PM and T1DM-noPM; however, earlier menarche might have an influence on PCOS diagnosis in women with T1DM.

Age at menarche and polycystic ovary syndrome: A Mendelian randomization study

“…The associations of AAM and the prevalence of PCOS have been previously explored. Sadrzadeh et al 9 found that patients diagnosed with PCOS had a significantly older AAM (15–18 years) (odds ratio [OR], 3.31 [95% CI, 2.18–5.04]), while a recent study showed that patients with type 1 diabetes on insulin treatment might be more susceptible to PCOS development, especially when their pubertal age onset was at 8 to 11 years, dominantly younger than their peers 10 …”

“…10 However, consensus still has not been reached regarding how AAM impacts the risk of PCOS. 9,10 In addition, the majority of published papers are epidemiologic and case-controlled studies, which are naturally with limitations in the causality clarification due to blurred temporal orders. In addition, it has been noted that published observational studies have failed to roll out violations from confounding risk factors, which might affect the confidence in conclusions to some extent.…”

“…Sadrzadeh et al 9 found that patients diagnosed with PCOS had a significantly older AAM (15-18 years) (odds ratio [OR], 3.31 [95% CI, 2.18-5.04]), while a recent study showed that patients with type 1 diabetes on insulin treatment might be more susceptible to PCOS development, especially when their pubertal age onset was at 8 to 11 years, dominantly younger than their peers. 10 However, consensus still has not been reached regarding how AAM impacts the risk of PCOS. 9,10 In addition, the majority of published papers are epidemiologic and case-controlled studies, which are naturally with limitations in the causality clarification due to blurred temporal orders.…”

“…However, consensus still has not been reached regarding how AAM impacts the risk of PCOS 9,10 . In addition, the majority of published papers are epidemiologic and case‐controlled studies, which are naturally with limitations in the causality clarification due to blurred temporal orders.…”

Genetic evidence for the causal association between type 1 diabetes and the risk of polycystic ovary syndrome

“…This leads to an inevitable therapeutic increase in the dose of insulin therapy, resulting in exogenous systemic hyperinsulinemia, which stimulates androgen over-synthesis and secretion in the ovaries and adrenal glands, which in turn may lead to the development of PCOS [ 16 ]. However, comparing different insulin treatment modalities did not reveal differences in the prevalence of PCOS and its symptoms [ 17 ]. In addition, comparisons between well-controlled and poorly controlled adolescents with T1D did not reveal differences in androgen concentrations and ovarian parameters [ 17 ].…”