Type 1 DiabetesNCT04979377
Prevalence of Hyperandrogenism in Type 1 Diabetes
An observational study of Type 1 Diabetes and Polycystic Ovary Syndrome, run by Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal at 1 site in Spain.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Type 1 Diabetes, Polycystic Ovary Syndrome, Hyperandrogenism
- What is being tested?
- Clinical hyperandrogenism assessment, Total testosterone (ng/dL) and A1c (%)
- How many people
- 150 participants
- Where
- 1 siteSpain
- Study dates
- 9 Mar 2020to 30 Dec 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Study population: Premenopausal women with T1DM consecutively recruited from a Diabetes outpatient clinic at a tertiary hospital.
Who may be able to join
- Age between 18 and 45 years old
- Type 1 diabetes diagnosed at least 1 year before the inclusion in the study. Diagnosis confirmed by positive autoimmunity (GAD-65 or IA2) and insulin deficiency.
- Treatment with subcutaneus insulin therapy (multiple dose or continuous subcutaneous insulin infusion).
- Menarche at least 2 years before the study.
Who cannot join
- Honey moon period.
- Altered thyroid hormone or prolactin levels.
- Congenital adrenal hyperplasia.
- Severe chronic disease.
- Oral contraceptive or glucocorticoid therapy in the previous 3 months.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Prevalence of Hyperandrogenism in Young Women With Type 1 Diabetes and Study of the Underlying Pathophysiological Mechanisms
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.
Read the detailed description
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.
- Conditions
- Type 1 Diabetes, Polycystic Ovary Syndrome, Hyperandrogenism, Hirsutism, Oligomenorrhea, Ovulation Disorder
- Being tested
- Clinical hyperandrogenism assessment, Total testosterone (ng/dL), A1c (%), Total cholesterol, Body mass index (BMI) (kg/m2)
- Keywords
- Polycystic ovary syndrome, Hyperandrogenism, Type 1 diabetes, Prevalence, Hirsutism, Ovulatory dysfunction, Testosterone, Insulin
- Medical subject headings
- Diabetes Mellitus, Type 1, Polycystic Ovary Syndrome, Hyperandrogenism, Hirsutism, Oligomenorrhea, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Clinical hyperandrogenism assessmentOther
Also called Hirsutism score
Modified Ferriman-Gallwey scale
Total testosterone (ng/dL)Diagnostic test
Also called Sex steroid profile
Circulating total testosterone (LC-MS/MS or IQL-CDC method) at follicular phase
A1c (%)Diagnostic test
Also called Metabolic control
High Performance Liquid Chromatography (HPLC)
Total cholesterolDiagnostic test
Also called Lipid profile
Determined by enzymatic methods
Body mass index (BMI) (kg/m2)Other
Also called Anthropometrics and body composition
Defined as body weight divided by the square of body height, and expressed in kg/m2
Frequency of chronic vascular complications [n (%)]Diagnostic test
Retinopathy, nephropathy, neuropathy, and macrovascular disease.
Polycystic ovary morphologyDiagnostic test
Sonographic assessment
Cardiovascular autonomic reflex tests (CARTs)Diagnostic test
Also called Cardiovascular function
Cardioautonomic function assessement by Vital scan HW7-HW6T:
Sex hormone-binding globulin (SHBG) (nmol/L)Diagnostic test
Also called Sex steroid profile
Circulating SHBG (IQL) at follicular phase
Dehydroepiandrosterone-sulphate (IQL) (ng/mL)Diagnostic test
Also called Sex steroid profile
Circulating DHEAS (IQL) at follicular phase
Waist circumference (cm)Other
Also called Anthropometrics and body composition
Waist circumference measurement made at the top of the iliac crest
Waist-to-hip ratioOther
Also called Anthropometrics and body composition
Waist circumference divided by hip circumference (measurement should be taken around the widest portion of the buttocks)
Body compositionOther
Also called Bioimpedanciometry
Vital Scan HW7-HW6T
Mean glucose (mg/dL)Diagnostic test
Also called Metabolic control
Continuous glucose monitoring (GCM) records
Time in target range (hours)Diagnostic test
Also called Metabolic control
Continuous glucose monitoring (GCM) records
Time in hyperglycemia (hours)Diagnostic test
Also called Metabolic control
Continuous glucose monitoring (GCM) records
Insulin dose (UI/Kg)Other
Also called Metabolic control
Daily insulin dose divided by body weight
Insulin sensitivityOther
Also called Estimated glucose disposal rate (eGDR)
Equation that relies on routine clinical measures: A1c, presence of hypertension, and waist circumference
High-density lipoprotein (HDL) (mg/dL)Diagnostic test
Also called HDL-cholesterol
Enzymatic methods after precipitation of serum with phosphotungstic acid and Mg2+
Low-density lipoprotein (LDL) (mg/dL)Diagnostic test
Also called Lipid profile
Estimated by the Friedewald's equation.
Triglycerides (mg/dL)Diagnostic test
Also called Lipid profile
Determined by enzymatic methods
| Study group | Role | What they receive |
|---|---|---|
| Adult premenopausal women with type 1 diabetes mellitus | 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 Receives: 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) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Prevalence of PCOS in T1DM
Prevalence of PCOS in women with T1DM according to ESHRE-ASRM/Rotterdam criteria
Measured: 2020-2022
Prevalence of classic PCOS in T1DM
Prevalence of PCOS in women with T1DM according to classic NIH criteria
Measured: 2020-2022
Prevalence of hyperandrogenic PCOS in T1DM
Prevalence of PCOS in women with T1DM according to AES-PCOS criteria
Measured: 2020-2022
Secondary outcomes (10)
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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 2020-2022
Influence of hyperandrogenism on insulin requirements
To describe the influence of hyperandrogenism on metabolic control.
Measured: 2020-2022
Influence of hyperandrogenism on A1c
To describe the influence of hyperandrogenism on metabolic control.
Measured: 2020-2022
Influence of hyperandrogenism on mean glucose (GCM)
To describe the influence of hyperandrogenism on metabolic control.
Measured: 2020-2022
Influence of hyperandrogenism on time in range (GCM)
To describe the influence of hyperandrogenism on metabolic control.
Measured: 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
Measured: 2020-2022
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2021
- Study start9 Mar 2020
- Primary completion30 Dec 2024
- Study completion30 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for Type 1 DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
- Sponsor type
- University, hospital or other
- Collaborators
- Hospital Universitario Ramon y Cajal, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders, University of Alcala, Instituto de Salud Carlos III
- Responsible party
- Principal investigator, Manuel Luque Ramírez, Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
- Investigators
- Manuel Luque-Ramírez, PhD, MD, MBA, Study director, CIBERDEM, Instituto de Salud Carlos IIIHéctor F Escobar-Morreale, PhD, MD, Study chair, University of Alcalá
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04979377
- Sponsor's protocol ID
- DM1PCOS
- Status last verified
- Mar 2025
- First submitted
- 7 Jul 2021
- Last updated
- 17 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- 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.
Publications
Escobar-Morreale HF, Roldan B, Barrio R, Alonso M, Sancho J, de la Calle H, Garcia-Robles R. High prevalence of the polycystic ovary syndrome and hirsutism in women with type 1 diabetes mellitus. J Clin Endocrinol Metab. 2000 Nov;85(11):4182-7. doi: 10.1210/jcem.85.11.6931.
PubMed 11095451Roldan B, Escobar-Morreale HF, Barrio R, de La Calle H, Alonso M, Garcia-Robles R, Sancho J. Identification of the source of androgen excess in hyperandrogenic type 1 diabetic patients. Diabetes Care. 2001 Jul;24(7):1297-9. doi: 10.2337/diacare.24.7.1297. No abstract available.
PubMed 11423519Codner E, Escobar-Morreale HF. Clinical review: Hyperandrogenism and polycystic ovary syndrome in women with type 1 diabetes mellitus. J Clin Endocrinol Metab. 2007 Apr;92(4):1209-16. doi: 10.1210/jc.2006-2641. Epub 2007 Feb 6.
PubMed 17284617Escobar-Morreale HF, Roldan-Martin MB. Type 1 Diabetes and Polycystic Ovary Syndrome: Systematic Review and Meta-analysis. Diabetes Care. 2016 Apr;39(4):639-48. doi: 10.2337/dc15-2577.
PubMed 27208367Codner E, Soto N, Lopez P, Trejo L, Avila A, Eyzaguirre FC, Iniguez G, Cassorla F. Diagnostic criteria for polycystic ovary syndrome and ovarian morphology in women with type 1 diabetes mellitus. J Clin Endocrinol Metab. 2006 Jun;91(6):2250-6. doi: 10.1210/jc.2006-0108. Epub 2006 Mar 28.
PubMed 16569737Codner E, Iniguez G, Villarroel C, Lopez P, Soto N, Sir-Petermann T, Cassorla F, Rey RA. Hormonal profile in women with polycystic ovarian syndrome with or without type 1 diabetes mellitus. J Clin Endocrinol Metab. 2007 Dec;92(12):4742-6. doi: 10.1210/jc.2007-1252. Epub 2007 Sep 25.
PubMed 17895317Gaete X, Vivanco M, Eyzaguirre FC, Lopez P, Rhumie HK, Unanue N, Codner E. Menstrual cycle irregularities and their relationship with HbA1c and insulin dose in adolescents with type 1 diabetes mellitus. Fertil Steril. 2010 Oct;94(5):1822-6. doi: 10.1016/j.fertnstert.2009.08.039. Epub 2009 Sep 30.
PubMed 19796762Codner E, Merino PM, Tena-Sempere M. Female reproduction and type 1 diabetes: from mechanisms to clinical findings. Hum Reprod Update. 2012 Sep-Oct;18(5):568-85. doi: 10.1093/humupd/dms024. Epub 2012 Jun 17.
PubMed 22709979Nattero-Chavez L, Alonso Diaz S, Jimenez-Mendiguchia L, Garcia-Cano A, Fernandez-Duran E, Dorado Avendano B, Escobar-Morreale HF, Luque-Ramirez M. Sexual Dimorphism and Sex Steroids Influence Cardiovascular Autonomic Neuropathy in Patients With Type 1 Diabetes. Diabetes Care. 2019 Nov;42(11):e175-e178. doi: 10.2337/dc19-1375. Epub 2019 Sep 17. No abstract available.
PubMed 31530659Teede HJ, Misso ML, Costello MF, Dokras A, Laven J, Moran L, Piltonen T, Norman RJ; International PCOS Network. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Hum Reprod. 2018 Sep 1;33(9):1602-1618. doi: 10.1093/humrep/dey256.
PubMed 30052961Escobar-Morreale HF, Carmina E, Dewailly D, Gambineri A, Kelestimur F, Moghetti P, Pugeat M, Qiao J, Wijeyaratne CN, Witchel SF, Norman RJ. Epidemiology, diagnosis and management of hirsutism: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome Society. Hum Reprod Update. 2012 Mar-Apr;18(2):146-70. doi: 10.1093/humupd/dmr042. Epub 2011 Nov 6.
PubMed 22064667Escobar-Morreale HF, Bayona A, Nattero-Chavez L, Luque-Ramirez M. Type 1 diabetes mellitus and polycystic ovary syndrome. Nat Rev Endocrinol. 2021 Dec;17(12):701-702. doi: 10.1038/s41574-021-00576-0. No abstract available.
PubMed 34561669
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevalence of Hyperandrogenism in Young Women With Type 1 Diabetes and Study of the Underlying Pathophysiological Mechanisms
- ClinicalTrials.gov ID
- NCT04979377
- Acronym / sponsor ID
- DM1PCOS
- Conditions
- Type 1 Diabetes, Polycystic Ovary Syndrome, Hyperandrogenism, Hirsutism, Oligomenorrhea, Ovulation Disorder
- Keywords
- Polycystic ovary syndrome, Hyperandrogenism, Type 1 diabetes, Prevalence, Hirsutism, Ovulatory dysfunction, Testosterone, Insulin
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y CajalUniversity, hospital or other
- Collaborators
- Hospital Universitario Ramon y Cajal, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders, University of Alcala, Instituto de Salud Carlos III
- Study start
- 9 Mar 2020 (actual)
- Primary completion
- 30 Dec 2024 (actual)
- Study completion
- 30 Dec 2024 (actual)
- First posted
- 28 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Adult premenopausal women with type 1 diabetes mellitus | – | 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)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 |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- Premenopausal women with T1DM consecutively recruited from a Diabetes outpatient clinic at a tertiary hospital.
Key inclusion criteria (4 listed)
- Age between 18 and 45 years old
- Type 1 diabetes diagnosed at least 1 year before the inclusion in the study. Diagnosis confirmed by positive autoimmunity (GAD-65 or IA2) and insulin deficiency.
- Treatment with subcutaneus insulin therapy (multiple dose or continuous subcutaneous insulin infusion).
- Menarche at least 2 years before the study.
Key exclusion criteria (5 listed)
- Honey moon period.
- Altered thyroid hormone or prolactin levels.
- Congenital adrenal hyperplasia.
- Severe chronic disease.
- Oral contraceptive or glucocorticoid therapy in the previous 3 months.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Clinical hyperandrogenism assessmentAlso: Hirsutism scoreModified Ferriman-Gallwey scale | Other | Adult premenopausal women with type 1 diabetes mellitus |
| Total testosterone (ng/dL)Also: Sex steroid profileCirculating total testosterone (LC-MS/MS or IQL-CDC method) at follicular phase | Diagnostic test | Adult premenopausal women with type 1 diabetes mellitus |
| A1c (%)Also: Metabolic controlHigh Performance Liquid Chromatography (HPLC) | Diagnostic test | Adult premenopausal women with type 1 diabetes mellitus |
| Total cholesterolAlso: Lipid profileDetermined by enzymatic methods | Diagnostic test | Adult premenopausal women with type 1 diabetes mellitus |
| Body mass index (BMI) (kg/m2)Also: Anthropometrics and body compositionDefined as body weight divided by the square of body height, and expressed in kg/m2 | Other | Adult premenopausal women with type 1 diabetes mellitus |
| Frequency of chronic vascular complications [n (%)]Retinopathy, nephropathy, neuropathy, and macrovascular disease. | Diagnostic test | Adult premenopausal women with type 1 diabetes mellitus |
| Polycystic ovary morphologySonographic assessment | Diagnostic test | Adult premenopausal women with type 1 diabetes mellitus |
| Cardiovascular autonomic reflex tests (CARTs)Also: Cardiovascular functionCardioautonomic function assessement by Vital scan HW7-HW6T: | Diagnostic test | Adult premenopausal women with type 1 diabetes mellitus |
| Sex hormone-binding globulin (SHBG) (nmol/L)Also: Sex steroid profileCirculating SHBG (IQL) at follicular phase | Diagnostic test | Adult premenopausal women with type 1 diabetes mellitus |
| Dehydroepiandrosterone-sulphate (IQL) (ng/mL)Also: Sex steroid profileCirculating DHEAS (IQL) at follicular phase | Diagnostic test | Adult premenopausal women with type 1 diabetes mellitus |
| Waist circumference (cm)Also: Anthropometrics and body compositionWaist circumference measurement made at the top of the iliac crest | Other | Adult premenopausal women with type 1 diabetes mellitus |
| Waist-to-hip ratioAlso: Anthropometrics and body compositionWaist circumference divided by hip circumference (measurement should be taken around the widest portion of the buttocks) | Other | Adult premenopausal women with type 1 diabetes mellitus |
| Body compositionAlso: BioimpedanciometryVital Scan HW7-HW6T | Other | Adult premenopausal women with type 1 diabetes mellitus |
| Mean glucose (mg/dL)Also: Metabolic controlContinuous glucose monitoring (GCM) records | Diagnostic test | Adult premenopausal women with type 1 diabetes mellitus |
| Time in target range (hours)Also: Metabolic controlContinuous glucose monitoring (GCM) records | Diagnostic test | Adult premenopausal women with type 1 diabetes mellitus |
| Time in hyperglycemia (hours)Also: Metabolic controlContinuous glucose monitoring (GCM) records | Diagnostic test | Adult premenopausal women with type 1 diabetes mellitus |
| Insulin dose (UI/Kg)Also: Metabolic controlDaily insulin dose divided by body weight | Other | Adult premenopausal women with type 1 diabetes mellitus |
| Insulin sensitivityAlso: Estimated glucose disposal rate (eGDR)Equation that relies on routine clinical measures: A1c, presence of hypertension, and waist circumference | Other | Adult premenopausal women with type 1 diabetes mellitus |
| High-density lipoprotein (HDL) (mg/dL)Also: HDL-cholesterolEnzymatic methods after precipitation of serum with phosphotungstic acid and Mg2+ | Diagnostic test | Adult premenopausal women with type 1 diabetes mellitus |
| Low-density lipoprotein (LDL) (mg/dL)Also: Lipid profileEstimated by the Friedewald's equation. | Diagnostic test | Adult premenopausal women with type 1 diabetes mellitus |
| Triglycerides (mg/dL)Also: Lipid profileDetermined by enzymatic methods | Diagnostic test | Adult premenopausal women with type 1 diabetes mellitus |
Primary outcome
Prevalence of PCOS in T1DM
Time frame: 2020-2022
Prevalence of PCOS in women with T1DM according to ESHRE-ASRM/Rotterdam criteria
Prevalence of classic PCOS in T1DM
Time frame: 2020-2022
Prevalence of PCOS in women with T1DM according to classic NIH criteria
Prevalence of hyperandrogenic PCOS in T1DM
Time frame: 2020-2022
Prevalence of PCOS in women with T1DM according to AES-PCOS criteria
10 secondary outcomes
Prevalence of related traits in women with T1D
Time frame: 2020-2022
Influence fo the onset of type 1 diabetes on hyperandrogenism
Time frame: 2020-2022
Influence of Insulin Requirements on hyperandrogenism
Time frame: 2020-2022
Influence of metabolic control on hyperandrogenism
Time frame: 2020-2022
Influence of body composition on hyperandrogenism
Time frame: 2020-2022
Influence of hyperandrogenism on insulin requirements
Time frame: 2020-2022
Influence of hyperandrogenism on A1c
Time frame: 2020-2022
Influence of hyperandrogenism on mean glucose (GCM)
Time frame: 2020-2022
Influence of hyperandrogenism on time in range (GCM)
Time frame: 2020-2022
Influence of hyperandrogenism on chronic complications
Time frame: 2020-2022
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2025.
- Background: PubMed 11095451Escobar-Morreale HF, Roldan B, Barrio R, Alonso M, Sancho J, de la Calle H, Garcia-Robles R. High prevalence of the polycystic ovary syndrome and hirsutism in women with type 1 diabetes mellitus. J Clin Endocrinol Metab. 2000 Nov;85(11):4182-7. doi: 10.1210/jcem.85.11.6931.
- Background: PubMed 11423519Roldan B, Escobar-Morreale HF, Barrio R, de La Calle H, Alonso M, Garcia-Robles R, Sancho J. Identification of the source of androgen excess in hyperandrogenic type 1 diabetic patients. Diabetes Care. 2001 Jul;24(7):1297-9. doi: 10.2337/diacare.24.7.1297. No abstract available.
- Background: PubMed 17284617Codner E, Escobar-Morreale HF. Clinical review: Hyperandrogenism and polycystic ovary syndrome in women with type 1 diabetes mellitus. J Clin Endocrinol Metab. 2007 Apr;92(4):1209-16. doi: 10.1210/jc.2006-2641. Epub 2007 Feb 6.
- Background: PubMed 27208367Escobar-Morreale HF, Roldan-Martin MB. Type 1 Diabetes and Polycystic Ovary Syndrome: Systematic Review and Meta-analysis. Diabetes Care. 2016 Apr;39(4):639-48. doi: 10.2337/dc15-2577.
- Background: PubMed 16569737Codner E, Soto N, Lopez P, Trejo L, Avila A, Eyzaguirre FC, Iniguez G, Cassorla F. Diagnostic criteria for polycystic ovary syndrome and ovarian morphology in women with type 1 diabetes mellitus. J Clin Endocrinol Metab. 2006 Jun;91(6):2250-6. doi: 10.1210/jc.2006-0108. Epub 2006 Mar 28.
- Background: PubMed 17895317Codner E, Iniguez G, Villarroel C, Lopez P, Soto N, Sir-Petermann T, Cassorla F, Rey RA. Hormonal profile in women with polycystic ovarian syndrome with or without type 1 diabetes mellitus. J Clin Endocrinol Metab. 2007 Dec;92(12):4742-6. doi: 10.1210/jc.2007-1252. Epub 2007 Sep 25.
- Background: PubMed 19796762Gaete X, Vivanco M, Eyzaguirre FC, Lopez P, Rhumie HK, Unanue N, Codner E. Menstrual cycle irregularities and their relationship with HbA1c and insulin dose in adolescents with type 1 diabetes mellitus. Fertil Steril. 2010 Oct;94(5):1822-6. doi: 10.1016/j.fertnstert.2009.08.039. Epub 2009 Sep 30.
- Background: PubMed 22709979Codner E, Merino PM, Tena-Sempere M. Female reproduction and type 1 diabetes: from mechanisms to clinical findings. Hum Reprod Update. 2012 Sep-Oct;18(5):568-85. doi: 10.1093/humupd/dms024. Epub 2012 Jun 17.
- Background: PubMed 31530659Nattero-Chavez L, Alonso Diaz S, Jimenez-Mendiguchia L, Garcia-Cano A, Fernandez-Duran E, Dorado Avendano B, Escobar-Morreale HF, Luque-Ramirez M. Sexual Dimorphism and Sex Steroids Influence Cardiovascular Autonomic Neuropathy in Patients With Type 1 Diabetes. Diabetes Care. 2019 Nov;42(11):e175-e178. doi: 10.2337/dc19-1375. Epub 2019 Sep 17. No abstract available.
- Background: PubMed 30052961Teede HJ, Misso ML, Costello MF, Dokras A, Laven J, Moran L, Piltonen T, Norman RJ; International PCOS Network. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Hum Reprod. 2018 Sep 1;33(9):1602-1618. doi: 10.1093/humrep/dey256.
- Background: PubMed 22064667Escobar-Morreale HF, Carmina E, Dewailly D, Gambineri A, Kelestimur F, Moghetti P, Pugeat M, Qiao J, Wijeyaratne CN, Witchel SF, Norman RJ. Epidemiology, diagnosis and management of hirsutism: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome Society. Hum Reprod Update. 2012 Mar-Apr;18(2):146-70. doi: 10.1093/humupd/dmr042. Epub 2011 Nov 6.
- Background: PubMed 34561669Escobar-Morreale HF, Bayona A, Nattero-Chavez L, Luque-Ramirez M. Type 1 diabetes mellitus and polycystic ovary syndrome. Nat Rev Endocrinol. 2021 Dec;17(12):701-702. doi: 10.1038/s41574-021-00576-0. No abstract available.
- Individual participant dataSharing planned: 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Manuel Luque-Ramírez, PhD, MD, MBA study director
CIBERDEM, Instituto de Salud Carlos III
Héctor F Escobar-Morreale, PhD, MD study chair
University of Alcalá
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Type 1 Diabetes and Polycystic Ovary Syndrome, run by Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Prevalence of PCOS in T1DM (time frame: 2020-2022). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04979377, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2025.