Phlebotomy and Polycystic Ovary Syndrome

Manuel Luque Ramírez

Status: Completed

Conditions: Metabolic Cardiovascular Syndrome; Hyperandrogenism

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

Study type: Interventional

Funder types: Other

Identifiers

NCT02460445

PI14/00649

Details and patient eligibility

About

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.

Enrollment: 37 patients

Sex: Female

Ages: 18 to 45 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. 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.

2. Combined oral contraceptive pill indication for treatment: i) hyperandrogenism-related dermo-cosmetic complaints with psychoemotional impact; ii) endometrial protection; and/or iii) contraception desire.

3. Scheduled phlebotomy acceptation if randomly allocated.

4. Signed informed consent.

Exclusion criteria

1. Contraindication for blood donation.
2. Plasma ferritin < 76 pmol/l and/or transferrin saturation percent < 15%.
3. Anemia (plasma hemoglobin < 12 g/dl or hematocrit < 36%).
4. Chronic kidney disease (eGFR < 60 ml/min per 1.73 m2).
5. Personal history of dyslipidemia, hypertension, prediabetes, diabetes mellitus, gestational diabetes or cardiovascular events.
6. Treatment with oral contraceptives, antiandrogens, insulin sensitizers, drugs that might interfere with blood pressure regulation, lipid profile or carbohydrate metabolism, and oral/parenteral iron therapy for the previous 3 months to inclusion.
7. Previous surgical treatment for PCOS.
8. History of blood donation for the previous 12 months to inclusion.
9. Current history of infectious disease, inflammatory disease, liver disease, neurologic disease or malignancy.
10. Eating disorders. Body mass index < 18.5 Kg/m2.
11. Hereditary hemochromatosis.
12. Celiac disease or malabsorptive disorder.
13. Contraindication for treatment with combined oral contraceptives.
14. Pregnancy.
15. Current smoking, recreational drug use or excessive alcohol consumption (> 40 g per day).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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37 participants in 2 patient groups

Intervention

Experimental group

Description:

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.

Treatment:

Drug: Cyproterone Acetate

Drug: ethinylestradiol

Procedure: Phlebotomy

Control

Active Comparator group

Description:

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

Treatment:

Drug: Cyproterone Acetate

Drug: ethinylestradiol