Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of
reproductive age, with an estimated prevalence of 6-15% of the general population
worldwide. This heterogeneous syndrome has significant cardio-metabolic, reproductive,
and psycho-emotional consequences, and therefore, a prompt recognition and management is
of paramount importance for these women. Despite hyperandrogenism is the cornerstone in
the pathophysiology of PCOS, this derangement is closely related to insulin resistance,
compensatory hyperinsulinemia, and abdominal adiposity. Hyperinsulinemia increases
androgen secretion by co-stimulating besides gonadotropins both ovary and adrenal
steroidogenesis, which leads to predominant visceral/abdominal fat deposition, and
further contributes to insulin resistance and hyperinsulinemia. In addition, PCOS has
been classically associated with metabolic alterations such as for overweight/obesity and
type 2 diabetes mellitus. However, type 1 diabetes mellitus (T1D) results from
autoimmune-mediated destruction of the pancreas, causing a complete insulin lack in most
patients. Intensive insulin therapy - a mandatory iatrogenic hyperinsulinism -, while
improving chronic glycemic control and prognosis, has led in recent years to the
appearance of "new" reproductive consequences in these patients, such as functional
hyperandrogenism and menstrual irregularity. This association is expected from the
stimulation of ovarian androgen production by exogenous insulin, which reaches the ovary
in supraphysiological concentrations. However, these studies present with a high
heterogeneity, and prevalence rates significantly vary depending on several variables
such as the criteria used for PCOS diagnosis, race/ethnicity, age of the study
population, and the prevalence of obesity, among others. In 2016, a systematic review
assessing the prevalence of PCOS in T1D was published, including 475 women with T1D from
9 studies. The results showed an overall prevalence of PCOS about 24% in T1D, higher than
reported in the general population. Other hyperandrogenic traits such as hirsutism (25%),
hyperandrogenaemia (24%), or ovulatory dysfunction (33%) were also common. Although PCOS
is one of the most common comorbidities in patients with T1D, there are a limited number
of publications in the literature. In summary, PCOS and functional hyperandrogenism
remain a condition to be explored thoroughly in these patients.
The investigators hypothesize that the prevalence of functional hyperandrogenism
including PCOS in Spanish women with T1D is higher than in women from the general
population. Furthermore, signs and symptoms of hyperandrogenism, and hyperandrogenemia
may be milder in patients with T1D compared to hyperandrogenic women from the general
population. Moreover, the occurrence of PCOS in these women may be influenced by insulin
dose, duration of diabetes, and chronic metabolic control.
The main objective of this study is to determine the actual prevalence of PCOS in
premenopausal women with T1DM, according to different diagnostic criteria/PCOS phenotypes
[classic PCOS (classic NIH criteria), hyperandrogenic PCOS (AES-PCOS criteria), and/or
inclusive ESHRE-ASRM/Rotterdam criteria]. As secondary goals, the investigators also aim
to describe: i) the hyperandrogenic traits associated with PCOS in women with T1DM; and
ii) the metabolic-T1D related parameters in women with or without hyperandrogenism.
Sample size calculation: Sample size analysis used the online sample size and power
calculator from the Program of Research in Inflammatory and Cardiovascular Disorders,
Institut Municipal d'Investigació Mèdica, Barcelona, Spain
(https://www.imim.cat/ofertadeserveis/software-public/granmo/). Considering previous data
on prevalence of SOP in adolescents and adult women with T1D according to
ESHRE-ASRM/Rotterdam criteria, the investigators concluded that 150 participants would be
needed to assume an expected proportion of 40%, with an absolute precision of 5% at both
sides of the proportion, and an asymptotic bilateral 95% confidence interval, and with an
estimated replacement rate of 10%.
Statistical analysis: Continuous variables will be expressed as mean ± SD with its
respective 95% confidence intervals (95%CI). Normality of continuous variables will be
checked by the Kolmogorov-Smirnov test, and ensured by applying logarithmic
transformations. the investigators will use non-parametric tests to analyse variables
that remained skewed even after transformation. The differences in means will be analysed
by Student t or Mann-Whitney U tests. Discrete variables will be showed according to
their absolute, relative frequency, and 95%CI determined using the Wilson method without
continuity correction. The differences between proportions will be estimated using the χ2
or Fisher's exact tests. Correlation analysis will be used to evaluate putative
association between continuous variables. Finally, multiple linear an binary logistic
regression full and stepwise models (probability for entry ≤0.05, probability for removal
≥0.10) will be performed to ascertain the main determinants of predetermined outcomes.
The statistical significance will be set at the P < 0.05 level.