Long-term use of contraceptive depot medroxyprogesterone acetate in young women impairs arterial endothelial function assessed by cardiovascular magnetic resonance

• Published in: Circulation (New York, N.Y.) Vol. 106; no. 13; pp. 1646 - 1651
• Main Authors: SORENSEN, Morten B, COLLINS, Peter, PENNELL, Dudley J, ONG, Paul J. L, WEBB, Carolyn M, HAYWARD, Christopher S, ASBURY, Elizabeth A, GATEHOUSE, Peter D, ELKINGTON, Andrew G, YANG, Guang Z, KUBBA, Ali
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 24.09.2002
• Subjects: Adult; Amenorrhea - chemically induced; Amenorrhea - complications; Biological and medical sciences; Brachial Artery - diagnostic imaging; Brachial Artery - drug effects; Brachial Artery - physiopathology; Delayed-Action Preparations - administration & dosage; Delayed-Action Preparations - adverse effects; Drug toxicity and drugs side effects treatment; Endothelium, Vascular - diagnostic imaging; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiopathology; Estradiol - blood; Female; Humans; Magnetic Resonance Angiography; Male; Medical sciences; Medroxyprogesterone Acetate - administration & dosage; Medroxyprogesterone Acetate - adverse effects; Middle Aged; Nitroglycerin; Pharmacology. Drug treatments; Reference Values; Reproducibility of Results; Time; Toxicity: cardiovascular system; Ultrasonography, Interventional; Vascular Diseases - chemically induced; Vascular Diseases - complications; Vascular Diseases - physiopathology; Vasomotor System - drug effects; Vasomotor System - physiopathology; Human; Toxicity; Sex; Nuclear magnetic resonance imaging; Endothelium; Chemotherapy; Treatment; Dysfunction; Medroxyprogesterone; Medical imagery; Female; Contraceptive; Age
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.cir.0000030940.73167.4e

Depot medroxyprogesterone acetate (DMPA) inhibits proliferation of ovarian follicles, resulting in anovulation and a decrease in circulating estrogen; the latter action is potentially disadvantageous to cardiovascular health. We therefore investigated the vascular effects of long-term contraceptive DMPA in young women. Endothelium-dependent (hyperemia-induced flow-mediated dilatation [FMD]) and -independent (glyceryl trinitrate [GTN]) changes in brachial artery area were measured using cardiovascular magnetic resonance in 13 amenorrheic DMPA users (>1 year use; mean age 29+/-4 years) and in 10 controls (mean age 30+/-4 years, P=0.25) with regular menstrual cycles after validation of the technique. FMD and GTN responses were measured just before repeat MPA injection and 48 hours later (n=12) in DMPA users and during menstruation and midcycle (n=9) in controls. Serum-estradiol levels (S-estradiol) were measured at both visits. FMD was reduced in DMPA users compared with controls during menstruation (1.1% versus 8.0%, respectively P<0.01) without differences in GTN responses. S-estradiol levels in DMPA users were significantly lower than in controls during menstruation (58 versus 96 pmol/L, P<0.01). High levels of circulating MPA 48 hours after injection were not linked to an additional impairment in FMD (2.0% versus 3.1%, P=0.23). Estradiol levels were significantly correlated to FMD (r=0.43, P<0.01). Endothelium-dependent arterial function measured by cardiovascular magnetic resonance is impaired in chronic users of DMPA, and hypoestrogenism may be the mechanism of action. DMPA might adversely affect cardiovascular health, and in particular its use in women with cardiovascular disease should be additionally evaluated.