Phlebotomy and Polycystic Ovary Syndrome

Hyperandrogenism Clinical Trial

Official title:

Effect of Decreasing Iron Tissue Depots on the Cardiovascular Risk of Women With Polycystic Ovary Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02460445
• Other study ID #: PI14/00649
• Status: Completed
• Phase: N/A
• Start date: January 2015
• Est. completion date: June 2020

Study information

• Verified date: July 2022
• Source: Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: June 2020
• Est. primary completion date: June 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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).

Related Conditions & MeSH terms

• Hyperandrogenism
• Metabolic Cardiovascular Syndrome
• Metabolic Syndrome
• Polycystic Ovary Syndrome
• Syndrome

Intervention

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

Drug:
• ethinylestradiol
35 mcg ethinylestradiol qd for 21 days per month as usual clinical practice.
• Cyproterone Acetate
2 mg cyproterone acetate qd for 21 days per month as usual clinical practice.

Locations

Country	Name	City	State
Spain	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

Sponsors (2)

Lead Sponsor	Collaborator
Manuel Luque Ramírez	Instituto de Salud Carlos III

Country where clinical trial is conducted

Spain, 

References & Publications (3)

Luque-Ramírez M, Ortiz-Flores AE, Martínez-García MÁ, Insenser M, Quintero-Tobar A, De Lope Quiñones S, Fernández-Durán E, Nattero-Chávez ML, Álvarez-Blasco F, Escobar-Morreale HF. Effect of Iron Depletion by Bloodletting vs. Observation on Oxidative Stre — View Citation

Luque-Ramírez M, Ortiz-Flores AE, Nattero-Chávez L, Martínez-García MÁ, Insenser M, Álvarez-Blasco F, Fernández-Durán E, Quintero-Tobar A, de Lope Quiñones S, Escobar-Morreale HF. Bloodletting has no effect on the blood pressure abnormalities of hyperandr — View Citation

Ortiz-Flores AE, Martínez-García MÁ, Nattero-Chávez L, Álvarez-Blasco F, Fernández-Durán E, Quintero-Tobar A, Escobar-Morreale HF, Luque-Ramírez M. Iron Overload in Functional Hyperandrogenism: In a Randomized Trial, Bloodletting Does Not Improve Metaboli — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Subclinical chronic inflammation		one year
Other	Oxidative stress		one year
Other	Autonomic vascular function		one year
Other	Blood clotting test		one year
Primary	Change in the Matsuda index from the circulating glucose and insulin concentrations during and standard oral glucose tolerance test.		one year
Primary	Percentage of patients with Hb < 12 g/dl or hematocrit <36% throughout the study		one year
Secondary	Change in the percentage of patients with undiagnosed prediabetes/diabetes between month 0 and 12 of follow-up		one year
Secondary	Change in the Disposition index between month 0 and 12 of follow-up		one year
Secondary	Change in the lipid profile between month 0 and 12 of follow-up		one year
Secondary	Changes in the blood pressure recordings between month 0 and 12 of follow-up		one year
Secondary	Percentage of patients with ferropenia throughout the study		one year
Secondary	Percentage of patients with a hypovolemic event during blood donation		one year