Phlebotomy and Polycystic Ovary Syndrome

NCT02460445 | Completed

• 1 other identifier: PI14/00649
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

AIMS To study the effects of the decrease in iron tissue depots after scheduled bloodletting on insulin sensitivity, carbohydrate metabolism, classic and non-classic cardiovascular risk factors in patients with functional hyperandrogenism (polycystic ovary syndrome \& idiopathic hyperandrogenism) on standard treatment with combined oral contraceptives (COC) according to usual clinical practice. METHODOLOGY Open label, controlled, parallel, prospective study of 12 months of duration, with 2 randomized arms of follow-up: i) Intervention Group: Patients with functional hyperandrogenism on standard COC treatment randomly allocated to perform scheduled phlebotomies from the third month of treatment to the end of the study (3 times with a 3-month interval between them). ii) Control Group: Patients with functional hyperandrogenism on standard COC treatment randomly allocated to follow-up without bloodletting. The whole group of patients will undergo a comprehensive anthropometric and hormonal assessment, evaluation of classic cardiovascular risk factors (insulin sensitivity and carbohydrate metabolism after a standard oral glucose test- 75 g), lipid profile, ambulatory and office blood pressure monitoring, proinflammatory profile, oxidative stress status, autonomic function assessment, and iron-related metabolism parameters at baseline, after 3-month COC treatment and after reduction of iron tissue depots plus OC in the Intervention Group of patients, and throughout follow-up under treatment with COC in the Control Group of patients. If a significant relationship between circulating hepcidin levels and elevated ferritin concentrations is observed, a study of the potential influence of mutations/polymorphic variants of hepcidin gene on ferritin values will be performed as well.

Conditions

Hyperandrogenism; Metabolic Cardiovascular Syndrome

Keywords

Functional hyperandrogenism; Polycystic ovary syndrome; Idiopathic hyperandrogenism; Iron tissue depots; Phlebotomy; Insulin resistance; Carbohydrate metabolism; Blood pressure; Autonomic dysfunction; Oxidative stress; Blood clotting tests; Efficacy; Side effects; Randomized clinical trial

Outcome Measures

Primary Outcomes (2)

• Change in the Matsuda index from the circulating glucose and insulin concentrations during and standard oral glucose tolerance test.

  one year

• Percentage of patients with Hb < 12 g/dl or hematocrit <36% throughout the study

  one year

Secondary Outcomes (6)

• Change in the percentage of patients with undiagnosed prediabetes/diabetes between month 0 and 12 of follow-up

  one year

• Change in the Disposition index between month 0 and 12 of follow-up

  one year

• Change in the lipid profile between month 0 and 12 of follow-up

  one year

• Changes in the blood pressure recordings between month 0 and 12 of follow-up

  one year

• Percentage of patients with ferropenia throughout the study

  one year

Other Outcomes (4)

• Subclinical chronic inflammation

  one year

• Oxidative stress

  one year

• Autonomic vascular function

  one year

Study Arms (2)

Intervention

EXPERIMENTAL

Premenopausal women with functional hyperandrogenism under combined oral contraceptive pill qd as usual clinical practice who will undergo a scheduled standard phlebotomy every 3 months from month 3 to 12 of follow-up.

Procedure: Phlebotomy; Drug: ethinylestradiol; Drug: Cyproterone Acetate

Control

ACTIVE COMPARATOR

Premenopausal women with functional hyperandrogenism under standard combined oral contraceptive pill qd as usual clinical practice.

Drug: ethinylestradiol; Drug: Cyproterone Acetate

Interventions

Phlebotomy PROCEDURE

Scheduled standard phlebotomy every three months from month 3 to 12 of follow-up.

Also known as: Blood donation, Bloodletting

Intervention

ethinylestradiol DRUG

35 mcg ethinylestradiol qd for 21 days per month as usual clinical practice.

Control; Intervention

Cyproterone Acetate DRUG

2 mg cyproterone acetate qd for 21 days per month as usual clinical practice.

Control; Intervention

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Premenopausal women with functional hyperandrogenism defined as:
• Polycystic ovary syndrome (PCOS): Clinical and biochemical hyperandrogenism plus ovulatory dysfunction or polycystic ovarian morphology.
• Idiopathic hyperandrogenism: Clinical and biochemical hyperandrogenism with normal ovulatory cycles and normal ovarian morphology.
• Combined oral contraceptive pill indication for treatment: i) hyperandrogenism-related dermo-cosmetic complaints with psychoemotional impact; ii) endometrial protection; and/or iii) contraception desire.
• Scheduled phlebotomy acceptation if randomly allocated.
• Signed informed consent.

You may not qualify if:

• Contraindication for blood donation.
• Plasma ferritin \< 76 pmol/l and/or transferrin saturation percent \< 15%.
• Anemia (plasma hemoglobin \< 12 g/dl or hematocrit \< 36%).
• Chronic kidney disease (eGFR \< 60 ml/min per 1.73 m2).
• Personal history of dyslipidemia, hypertension, prediabetes, diabetes mellitus, gestational diabetes or cardiovascular events.
• Previous surgical treatment for PCOS.
• Current history of infectious disease, inflammatory disease, liver disease, neurologic disease or malignancy.
• Eating disorders. Body mass index \< 18.5 Kg/m2.
• Hereditary hemochromatosis.
• Celiac disease or malabsorptive disorder.
• Contraindication for treatment with combined oral contraceptives.
• Pregnancy.
• Current smoking, recreational drug use or excessive alcohol consumption (\> 40 g per day).

Sponsors & Collaborators

• Manuel Luque Ramírez: lead
• Instituto de Salud Carlos III: collaborator

Study Sites (1)

Diabetes, Obesity and Human Reproduction Research Group, Department of Endocrinology and Nutrition, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS)

Madrid, 28034, Spain

Location

Related Publications (3)

• Ortiz-Flores AE, Martinez-Garcia MA, Nattero-Chavez L, Alvarez-Blasco F, Fernandez-Duran E, Quintero-Tobar A, Escobar-Morreale HF, Luque-Ramirez M. Iron Overload in Functional Hyperandrogenism: In a Randomized Trial, Bloodletting Does Not Improve Metabolic Outcomes. J Clin Endocrinol Metab. 2021 Mar 25;106(4):e1559-e1573. doi: 10.1210/clinem/dgaa978.

  PMID: 33462622 RESULT

• Luque-Ramirez M, Ortiz-Flores AE, Nattero-Chavez L, Martinez-Garcia MA, Insenser M, Alvarez-Blasco F, Fernandez-Duran E, Quintero-Tobar A, de Lope Quinones S, Escobar-Morreale HF. Bloodletting has no effect on the blood pressure abnormalities of hyperandrogenic women taking oral contraceptives in a randomized clinical trial. Sci Rep. 2021 Nov 11;11(1):22097. doi: 10.1038/s41598-021-01606-7.

  PMID: 34764381 RESULT

• Luque-Ramirez M, Ortiz-Flores AE, Martinez-Garcia MA, Insenser M, Quintero-Tobar A, De Lope Quinones S, Fernandez-Duran E, Nattero-Chavez ML, Alvarez-Blasco F, Escobar-Morreale HF. Effect of Iron Depletion by Bloodletting vs. Observation on Oxidative Stress Biomarkers of Women with Functional Hyperandrogenism Taking a Combined Oral Contraceptive: A Randomized Clinical Trial. J Clin Med. 2022 Jul 3;11(13):3864. doi: 10.3390/jcm11133864.

  PMID: 35807149 RESULT

MeSH Terms

Conditions

Hyperandrogenism; Metabolic Syndrome; Polycystic Ovary Syndrome; Insulin Resistance; Primary Dysautonomias

Interventions

Phlebotomy; Blood Donation; Bloodletting; Ethinyl Estradiol; Cyproterone Acetate

Condition Hierarchy (Ancestors)

46, XX Disorders of Sex Development; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Adrenogenital Syndrome; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Gonadal Disorders; Endocrine System Diseases; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Genital Diseases; Autonomic Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Blood Specimen Collection; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Therapeutics; Surgical Procedures, Operative; Investigative Techniques; Tissue and Organ Procurement; Health Services; Health Care Facilities Workforce and Services; Norpregnatrienes; Norpregnanes; Norsteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estrogenic Steroids, Alkylated; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Cyproterone; Pregnadienes; Pregnanes; Steroids, Chlorinated

Study Officials

• Manuel Luque Ramírez, M.D., Ph.D.

  Assistant in Endocrinology. Member of the Diabetes, Obesity and Human Reproduction Research Group from the lnstituto Ramón y Cajal de Investigación Sanitaria (IRYCIS)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Member of the Diabetes, Obesity and Human Reproduction Research Group, Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas CIBERDEM.

Study Record Dates

• First Submitted: May 27, 2015
• First Posted: June 2, 2015
• Study Start: January 1, 2015
• Primary Completion: June 1, 2020
• Study Completion: June 1, 2020
• Last Updated: July 27, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: With publication
• Access Criteria: Data are available from PI on reasonable request (manuel.luque@salud.madrid.org)

Locations

ES (1)