An observational study in Type 1 Diabetes, Polycystic Ovary Syndrome and Hyperandrogenism, sponsored by Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal. Completed at 1 site in Spain. Open to female participants aged 18 Years to 45 Years. Per ClinicalTrials.gov, last updated 2025-03-17.
Sponsored by Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal · Observational
The investigators aim to estimate the prevalence of functional ovarian hyperandrogenism [idiopathic hyperandrogenism, idiopatic hirsutism, and polycystic ovary syndrome (PCOS)] in adult patients with type 1 diabetes (T1DM) in an observational cross-sectional study. Study population is comprised of premenopausal adult women with a diagnosis of T1DM, consecutively recruited from a Diabetes outpatient clinic at a tertiary hospital in Spain, Europe.
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.
3,754 studies on the registry are indexed under Diabetes Mellitus, Type 1; 600 are open to participants now.
This study's enrollment of 150 is above the median of 125 across 792 observational studies indexed under Diabetes Mellitus, Type 1.
Browse Diabetes Mellitus, Type 1 studies →Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal is the lead sponsor of 83 studies on the registry; 22 are open to participants now.
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Premenopausal women with T1DM consecutively recruited from a Diabetes outpatient clinic at a tertiary hospital.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
One-hundred and fifty women aged from 18 to 45 years old consecutively recruited from a type 1 diabetes clinic at a tertiary hospital of Madrid, Spain
Other: Clinical hyperandrogenism assessment · Diagnostic Test: Total testosterone (ng/dL) · Diagnostic Test: A1c (%) · Diagnostic Test: Total cholesterol · Other: Body mass index (BMI) (kg/m2) · Diagnostic Test: Frequency of chronic vascular complications [n (%)] · Diagnostic Test: Polycystic ovary morphology · Diagnostic Test: Cardiovascular autonomic reflex tests (CARTs) · Diagnostic Test: Sex hormone-binding globulin (SHBG) (nmol/L) · Diagnostic Test: Dehydroepiandrosterone-sulphate (IQL) (ng/mL) · Other: Waist circumference (cm) · Other: Waist-to-hip ratio · Other: Body composition · Diagnostic Test: Mean glucose (mg/dL) · Diagnostic Test: Time in target range (hours) · Diagnostic Test: Time in hyperglycemia (hours) · Other: Insulin dose (UI/Kg) · Other: Insulin sensitivity · Diagnostic Test: High-density lipoprotein (HDL) (mg/dL) · Diagnostic Test: Low-density lipoprotein (LDL) (mg/dL) · Diagnostic Test: Triglycerides (mg/dL)
Modified Ferriman-Gallwey scale
Also known as: Hirsutism score
Circulating total testosterone (LC-MS/MS or IQL-CDC method) at follicular phase
Also known as: Sex steroid profile
High Performance Liquid Chromatography (HPLC)
Also known as: Metabolic control
Determined by enzymatic methods
Also known as: Lipid profile
Defined as body weight divided by the square of body height, and expressed in kg/m2
Also known as: Anthropometrics and body composition
Retinopathy, nephropathy, neuropathy, and macrovascular disease.
Sonographic assessment
Cardioautonomic function assessement by Vital scan HW7-HW6T:
Also known as: Cardiovascular function
Circulating SHBG (IQL) at follicular phase
Also known as: Sex steroid profile
Circulating DHEAS (IQL) at follicular phase
Also known as: Sex steroid profile
Waist circumference measurement made at the top of the iliac crest
Also known as: Anthropometrics and body composition
Waist circumference divided by hip circumference (measurement should be taken around the widest portion of the buttocks)
Also known as: Anthropometrics and body composition
Vital Scan HW7-HW6T
Also known as: Bioimpedanciometry
Continuous glucose monitoring (GCM) records
Also known as: Metabolic control
Continuous glucose monitoring (GCM) records
Also known as: Metabolic control
Continuous glucose monitoring (GCM) records
Also known as: Metabolic control
Daily insulin dose divided by body weight
Also known as: Metabolic control
Equation that relies on routine clinical measures: A1c, presence of hypertension, and waist circumference
Also known as: Estimated glucose disposal rate (eGDR)
Enzymatic methods after precipitation of serum with phosphotungstic acid and Mg2+
Also known as: HDL-cholesterol
Estimated by the Friedewald's equation.
Also known as: Lipid profile
Determined by enzymatic methods
Also known as: Lipid profile
Prevalence of PCOS in T1DM
Prevalence of PCOS in women with T1DM according to ESHRE-ASRM/Rotterdam criteria
Time frame: 2020-2022
Prevalence of classic PCOS in T1DM
Prevalence of PCOS in women with T1DM according to classic NIH criteria
Time frame: 2020-2022
Prevalence of hyperandrogenic PCOS in T1DM
Prevalence of PCOS in women with T1DM according to AES-PCOS criteria
Time frame: 2020-2022
Prevalence of related traits in women with T1D
Prevalence of related hyperandrogenic traits (idiopatic hirsutism, hyperandrogenemia, oligomenorrhea and isolated polycytic ovarian morphology) in women with T1DM
Time frame: 2020-2022
Influence fo the onset of type 1 diabetes on hyperandrogenism
To assess the influence of the timing of diagnosis of type 1 diabetes in the appearance of hyperandrogenism, and also the possible effect of duration of diabetes.
Time frame: 2020-2022
Influence of Insulin Requirements on hyperandrogenism
To describe daily insulin requirements and their influence on functional hyperandrogenism occurrence. We also aim to determine the effect of the chronic metabolic control in PCOS appearance.
Time frame: 2020-2022
Influence of metabolic control on hyperandrogenism
To describe the influence of metabolic control (A1c) on functional hyperandrogenism occurrence. We also aim to determine the effect of the chronic metabolic control in PCOS appearance.
Time frame: 2020-2022
Influence of body composition on hyperandrogenism
To evaluate the influence of risk factors body composition in the occurrence of ovarian hyperandrogenism and PCOS in women with type 1 diabetes.
Time frame: 2020-2022
Influence of hyperandrogenism on insulin requirements
To describe the influence of hyperandrogenism on metabolic control.
Time frame: 2020-2022
Influence of hyperandrogenism on A1c
To describe the influence of hyperandrogenism on metabolic control.
Time frame: 2020-2022
Influence of hyperandrogenism on mean glucose (GCM)
To describe the influence of hyperandrogenism on metabolic control.
Time frame: 2020-2022
Influence of hyperandrogenism on time in range (GCM)
To describe the influence of hyperandrogenism on metabolic control.
Time frame: 2020-2022
Influence of hyperandrogenism on chronic complications
To describe the influence of hyperandrogenism on the frequency of chronic complications related to type 1 diabetes mellitus
Time frame: 2020-2022
Plan to share: Yes — All data sets generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report, Analytic code
Time frame: Since study ending with no time limit restriction
Access criteria: Reasonable request
Ran from Mar 2020 to primary completion in Dec 2024, 57 months.
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This study is completed, as verified in Mar 2025. You cannot join it, but the record below documents what was studied.
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Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal