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The effect of medroxyprogesterone acetate on estrogen-dependent risks and benefits--an attempt to interpret the Women's Health Initiative results.
Gynecol Endocrinol. 2006 Jun; 22(6):303-17.GE

Abstract

The results of the two arms of the Women's Health Initiative (WHI) study allow a comparative assessment of the contribution of the progestogen component to the changes in risk of cardiovascular disease and cancer during treatment of postmenopausal women with conjugated equine estrogens and medroxyprogesterone acetate (CEE/MPA). However, the high proportion of older and overweight or obese women compromises any conclusions, since we estimate that 50% of the women would have the metabolic syndrome. In overweight postmenopausal women with hyperinsulinemia, the risk of breast cancer is elevated and cannot be increased further by hormone replacement therapy (HRT). Therefore, the non-significant, but consistent reduction in breast cancer risk during treatment with CEE alone might be based on an improvement of hyperinsulinemia. The 24% increase in breast cancer risk in the CEE/MPA group can be regarded as an artifact due to very low numbers of breast cancer diagnoses in the placebo group of women who had received HRT prior to the WHI study. The elevated risk of venous thromboembolism and the transient increase in the risk of coronary heart disease (CHD) during treatment with CEE/MPA but not CEE alone suggests a direct effect of MPA on the vessel wall. MPA has been demonstrated to upregulate the thrombin receptor, the thrombin-induced production of tissue factor and procoagulatory activity in the vessel wall owing to its glucocorticoid activity. In contrast, CEE alone reduced non-significantly the risk of CHD in women aged 50-59 years, suggesting that primary prevention is possible if estrogen replacement therapy is initiated early. As clinical studies on the effect of different progestogens combined with estrogens are scarce, a possible superiority of progestogens other than MPA remains to be proven.

Authors+Show Affiliations

Department of Obstetrics and Gynecology, J. W. Goethe University, Frankfurt am Main, Germany. h.kuhl@em.uni-frankfurt.deNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16785155

Citation

Kuhl, Herbert, and John Stevenson. "The Effect of Medroxyprogesterone Acetate On Estrogen-dependent Risks and Benefits--an Attempt to Interpret the Women's Health Initiative Results." Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology, vol. 22, no. 6, 2006, pp. 303-17.
Kuhl H, Stevenson J. The effect of medroxyprogesterone acetate on estrogen-dependent risks and benefits--an attempt to interpret the Women's Health Initiative results. Gynecol Endocrinol. 2006;22(6):303-17.
Kuhl, H., & Stevenson, J. (2006). The effect of medroxyprogesterone acetate on estrogen-dependent risks and benefits--an attempt to interpret the Women's Health Initiative results. Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology, 22(6), 303-17.
Kuhl H, Stevenson J. The Effect of Medroxyprogesterone Acetate On Estrogen-dependent Risks and Benefits--an Attempt to Interpret the Women's Health Initiative Results. Gynecol Endocrinol. 2006;22(6):303-17. PubMed PMID: 16785155.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effect of medroxyprogesterone acetate on estrogen-dependent risks and benefits--an attempt to interpret the Women's Health Initiative results. AU - Kuhl,Herbert, AU - Stevenson,John, PY - 2006/6/21/pubmed PY - 2006/11/15/medline PY - 2006/6/21/entrez SP - 303 EP - 17 JF - Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology JO - Gynecol. Endocrinol. VL - 22 IS - 6 N2 - The results of the two arms of the Women's Health Initiative (WHI) study allow a comparative assessment of the contribution of the progestogen component to the changes in risk of cardiovascular disease and cancer during treatment of postmenopausal women with conjugated equine estrogens and medroxyprogesterone acetate (CEE/MPA). However, the high proportion of older and overweight or obese women compromises any conclusions, since we estimate that 50% of the women would have the metabolic syndrome. In overweight postmenopausal women with hyperinsulinemia, the risk of breast cancer is elevated and cannot be increased further by hormone replacement therapy (HRT). Therefore, the non-significant, but consistent reduction in breast cancer risk during treatment with CEE alone might be based on an improvement of hyperinsulinemia. The 24% increase in breast cancer risk in the CEE/MPA group can be regarded as an artifact due to very low numbers of breast cancer diagnoses in the placebo group of women who had received HRT prior to the WHI study. The elevated risk of venous thromboembolism and the transient increase in the risk of coronary heart disease (CHD) during treatment with CEE/MPA but not CEE alone suggests a direct effect of MPA on the vessel wall. MPA has been demonstrated to upregulate the thrombin receptor, the thrombin-induced production of tissue factor and procoagulatory activity in the vessel wall owing to its glucocorticoid activity. In contrast, CEE alone reduced non-significantly the risk of CHD in women aged 50-59 years, suggesting that primary prevention is possible if estrogen replacement therapy is initiated early. As clinical studies on the effect of different progestogens combined with estrogens are scarce, a possible superiority of progestogens other than MPA remains to be proven. SN - 0951-3590 UR - https://www.unboundmedicine.com/medline/citation/16785155/The_effect_of_medroxyprogesterone_acetate_on_estrogen_dependent_risks_and_benefits__an_attempt_to_interpret_the_Women's_Health_Initiative_results_ L2 - http://www.tandfonline.com/doi/full/10.1080/09513590600717368 DB - PRIME DP - Unbound Medicine ER -