Comparison of the effects of an oral contraceptive with those of a combined therapy with insulin sensitizers and anti-androgens in young girls with ovarian androgen excess and without pregnancy risk, on markers of cardiometabolic health

Conditions

Hyperinsulinemic androgen excess in adolescent girls Nutritional, Metabolic, Endocrine Androgen excess

Cristina García-Beltrán, Marion Peyrou, F E de Zegher, Abel López‐Bermejo, Francesc Villarroya et al. (6 authors)

Journal of the Endocrine Society2024-10-01

10.1210/jendso/bvae163.1645

6420 Organokines and Liver Enzymes in Adolescent Girls with Polycystic Ovary Syndrome During Randomized Treatments

Cristina García-Beltrán, Marion Peyrou, F E de Zegher, Abel López‐Bermejo, Francesc Villarroya et al. (6 authors)

Journal of the Endocrine Society2024-10-01

10.1210/jendso/bvae163.1732

Organokines and liver enzymes in adolescent girls with polycystic ovary syndrome during randomized treatments

Cristina García-Beltrán, Marion Peyrou, Artur Navarro‐Gascon, Abel López‐Bermejo, Francis de Zegher et al. (7 authors)

Frontiers in Endocrinology2024-05-165 citations

10.3389/fendo.2024.1325230

Adolescent polycystic ovary syndrome without obesity: HOTAIR rs1443512 genotype relates to fat mass and to the redistribution of fat mass on low-dose pioglitazone.

de Zegher F, Díaz M, Ibáñez L.

2023-10-086 citations

10.1007/s40618-023-02206-0

SPIOMET4HEALTH-efficacy, tolerability and safety of lifestyle intervention plus a fixed dose combination of spironolactone, pioglitazone and metformin (SPIOMET) for adolescent girls and young women with polycystic ovary syndrome: study protocol for a multicentre, randomised, double-blind, placebo-controlled, four-arm, parallel-group, phase II clinical trial.

Garcia-Beltran C, Malpique R, Andersen MS, Bas F, Bassols J, Darendeliler F, Díaz M, Dieris B, Fanelli F, Fröhlich-Reiterer E, Gambineri A, Glintborg D, López-Bermejo A, Mann C, Marin S, Obermayer-Pietsch B, Ødegård R, Ravn P, Reinehr T, Renzulli M, Salvador C, Singer V, Vanky E, Torres JV, Yildiz M, de Zegher F, Ibáñez L.

2023-09-152 citations

10.1186/s13063-023-07593-6

The relative deficit of GDF15 in adolescent girls with PCOS can be changed into an abundance that reduces liver fat.

de Zegher F, Díaz M, Villarroya J, Cairó M, López-Bermejo A, Villarroya F, Ibáñez L.

2021-03-2914 citations

10.1038/s41598-021-86317-9

Interventions

In this single-centre, open-labelled, controlled trial, the randomization (1:1) will be web-based (http://www.SealedEnvelope.com), using random permuted blocks, with strata for age (<16.0 or =16.0 yea

20 mcg ethinylestradiol plus 100 mg levonorgestrel for 21/28 days, and placebo for 7/28 days) or SPIOMET, a low-dose combination of separate generics: 50 mg spironolactone (one half of a 100 mg tablet

7.5 mg pioglitazone (one half of a 15 mg tablet of Actos from Takeda, Madrid, Spain)

and 850 mg metformin (one full 850 mg tablet of Metformina from Sandoz, Barcelona, Spain). The randomization will be performed by an investigator who will not be based in the recruiting hospital and

Eligibility

Sex/Gender

Female

Inclusion criteria

Inclusion criteria: 1. Hyperinsulinemia, defined as fasting insulinemia >15 IU/mL and/or a peak insulinemia >150 IU/mL and/or mean insulinemia >84 IU/mL on a 2-hour oral glucose tolerance test (oGTT) 2. Presence of both clinical and endocrine androgen excess, as defined by hirsutism score >8 (Ferriman-Gallwey scale), amenorrhea (no menses for more than 3 months) or oligomenorrhea (menstrual intervals >45 days), and high circulating concentrations of testosterone in the follicular phase (cycle day 3-7) or after 2 months of amenorrhea

Exclusion criteria

Exclusion criteria: 1. Pregnancy risk (throughout the study) 2. Anemia or bleeding disorder 3. Evidence of thyroid, liver or kidney dysfunction; abnormal electrolytes 4. Hyperprolactinemia 5. 21-hydroxylase deficiency (17-hydroxyprogesterone levels = 200 ng/dL in the follicular phase or after two months of amenorrhea) 6. Glucose intolerance or diabetes mellitus 7. Use of medication affecting gonadal or adrenal function, or carbohydrate or lipid metabolism

Design outcomes

Primary

Measure	Time frame
Current primary outcome measures as of 14/09/2018: 1. Insulinemia assessed by immunochemiluminescence every 6 months while on treatment and 6 months after end of treatment 2. Visceral and hepatic fat assessed by MRI every 6 months while on treatment and 6 months after end of treatment Post-treatment endpoints: 3. Ovulation rates assessed by ELISA of weekly salivary progesterone during the second and fourth quarter of the follow-up year Previous primary outcome measures as of 07/03/2016: On-treatment endpoints: 1. Insulinemia: on treatment every 6 months; 6 months off treatment. Method: immunoquimioluminescence 2. Visceral & hepatic fat: MRI. on treatment every 6 months; 6 months off treatment Post-treatment endpoints: 3. Ovulation rates Previous primary outcome measures: 1. Insulinemia: on treatment every 6 months; 6 months off treatment. Method: immunoquimioluminescence 2. Visceral & hepatic fat: MRI. on treatment every 6 months; 6 months off treatment	—

Measure

Time frame

Current primary outcome measures as of 14/09/2018: 1. Insulinemia assessed by immunochemiluminescence every 6 months while on treatment and 6 months after end of treatment 2. Visceral and hepatic fat assessed by MRI every 6 months while on treatment and 6 months after end of treatment Post-treatment endpoints: 3. Ovulation rates assessed by ELISA of weekly salivary progesterone during the second and fourth quarter of the follow-up year Previous primary outcome measures as of 07/03/2016: On-treatment endpoints: 1. Insulinemia: on treatment every 6 months; 6 months off treatment. Method: immunoquimioluminescence 2. Visceral & hepatic fat: MRI. on treatment every 6 months; 6 months off treatment Post-treatment endpoints: 3. Ovulation rates Previous primary outcome measures: 1. Insulinemia: on treatment every 6 months; 6 months off treatment. Method: immunoquimioluminescence 2. Visceral & hepatic fat: MRI. on treatment every 6 months; 6 months off treatment

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Secondary

Measure	Time frame
Current secondary outcome measures as of 17/09/2018: On-treatment endpoints: 1. Measures of androgen excess: hirsutism (Ferriman & Gallwey score); acne (Leeds score); testosterone (immunochemiluminescence), and AMH (ELISA) at baseline and after 12 months on treatment. 2. Measurements of cardio-metabolic risk: C-reactive protein (Architect c8000; Abbott); HMW adiponectin (ELISA), carotid intima-media thickness (ultrasound); insulinemia (Immunochemiluminiscence); visceral and hepatic fat (MRI); HMW adiponectin (ELISA), S100A4 (ELISA), at baseline and after 12 months of treatment. Post-treatment endpoints: 3. Measures of androgen excess: hirsutism (Ferriman & Gallwey score); acne (Leeds score); testosterone (immunochemiluminescence) and AMH (ELISA) after 6 and 12 months off treatment. 4. Measurements of cardio-metabolic risk: C-reactive protein (Architect c8000; Abbott); HMW adiponectin (ELISA), carotid intima-media thickness (ultrasound); insulinemia (Immunochemiluminiscence); visceral and hepatic fat (MRI); HMW adiponectin (ELISA), S100A4 (ELISA), at 6 and 12 months off treatment. Previous secondary outcome measures as of 13/09/2018: On-treatment endpoints: 1. Measures of androgen excess: hirsutism (Ferriman & Gallwey score); acne (Leeds score); testosterone (immunochemiluminescence) 2. C-reactive protein (Architect c8000; Abbott); HMW adiponectin (ELISA), carotid intima-media thickness (ultrasound) Post-treatment endpoints: 3. Insulinemia 4. Visceral & hepatic fat 5. Measures of androgen excess 6. C-reactive protein, HMW adiponectin, carotid intima-media thickness 7. Serum S100A4 on treatment 8. Anti-Mullerian hormone (AMH) at baseline and after 12 months on treatment Previous secondary outcome measures as of 07/03/2016: On-treatment endpoints: 1. Measures of androgen excess: hirsutism (Ferriman & Gallwey score); acne (Leeds score); testosterone (immunochemiluminescence) 2. C-reactive protein (Architect c8000; Abbott); HMW adiponectin (ELISA), carotid intima-me	—

Measure

Time frame

Current secondary outcome measures as of 17/09/2018: On-treatment endpoints: 1. Measures of androgen excess: hirsutism (Ferriman & Gallwey score); acne (Leeds score); testosterone (immunochemiluminescence), and AMH (ELISA) at baseline and after 12 months on treatment. 2. Measurements of cardio-metabolic risk: C-reactive protein (Architect c8000; Abbott); HMW adiponectin (ELISA), carotid intima-media thickness (ultrasound); insulinemia (Immunochemiluminiscence); visceral and hepatic fat (MRI); HMW adiponectin (ELISA), S100A4 (ELISA), at baseline and after 12 months of treatment. Post-treatment endpoints: 3. Measures of androgen excess: hirsutism (Ferriman & Gallwey score); acne (Leeds score); testosterone (immunochemiluminescence) and AMH (ELISA) after 6 and 12 months off treatment. 4. Measurements of cardio-metabolic risk: C-reactive protein (Architect c8000; Abbott); HMW adiponectin (ELISA), carotid intima-media thickness (ultrasound); insulinemia (Immunochemiluminiscence); visceral and hepatic fat (MRI); HMW adiponectin (ELISA), S100A4 (ELISA), at 6 and 12 months off treatment. Previous secondary outcome measures as of 13/09/2018: On-treatment endpoints: 1. Measures of androgen excess: hirsutism (Ferriman & Gallwey score); acne (Leeds score); testosterone (immunochemiluminescence) 2. C-reactive protein (Architect c8000; Abbott); HMW adiponectin (ELISA), carotid intima-media thickness (ultrasound) Post-treatment endpoints: 3. Insulinemia 4. Visceral & hepatic fat 5. Measures of androgen excess 6. C-reactive protein, HMW adiponectin, carotid intima-media thickness 7. Serum S100A4 on treatment 8. Anti-Mullerian hormone (AMH) at baseline and after 12 months on treatment Previous secondary outcome measures as of 07/03/2016: On-treatment endpoints: 1. Measures of androgen excess: hirsutism (Ferriman & Gallwey score); acne (Leeds score); testosterone (immunochemiluminescence) 2. C-reactive protein (Architect c8000; Abbott); HMW adiponectin (ELISA), carotid intima-me

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Countries

Spain

Outcome results

None listed