Dose Effects of Hormone Therapy (Two Doses of Estradiol Associated to Progesterone) on Inflammatory Markers

Condition(s) targeted: Healthy Symptomatic Menopausal Women

Intervention: CLIMASTON (drug) (Drug); 17 Beta-estradiol (2mg/day)and (1mg/day) (Drug); placebo (Drug)

Phase: Phase 3

Status: Terminated

Sponsored by: Assistance Publique - Hôpitaux de Paris

Official(s) and/or principal investigator(s):
Tabassome Simon, M.D., Ph.D., Principal Investigator, Affiliation: Service de Pharmacologie (Pr Jaillon) CHU Saint-Antoine 27, rue de Chaligny, 75012 Paris

Primary purpose : Effects of two doses of hormone therapy on hsCRP. The effects of hormone replacement therapy on inflammatory markers are dose-dependent.

Official title: Pro-Inflammatory Effects of Two Different Doses of 17 Beta Estradiol in Menopausal Women

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Pharmacodynamics Study

Primary outcome: Hs-C-reactive protein

Secondary outcome:

Interleukin (IL-6, IL-18, IL-10), TNF-alpha, apoptotic microparticles, homocysteine, total cholesterol/HDL cholesterol, Lp(a), interleukin 6, ICAM soluble,

Eslectin, prothrombin F1+2, factor VIII, resistance to activated protein C (RPCA or ACV test),IL 18, IL10, IL8

Detailed description: Pro-inflammatory study of the effects in short term of two difference doses of 17beta-estradiol at the menopause woman

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Female.

Criteria:

Inclusion Criteria:

- Symptomatic menopausal women : >=50 years and amenorrhea >=1 year or <50 years and

amenorrhea >=1 year and plasmatic FSH >= 30 UI/l

- Normal mammography in the last 2 years before inclusion

- Normal cervical smear in the last 2 years before inclusion

- Written consent for participation in the study

Exclusion Criteria:

- Unconfirmed Menopause with amenorrhoea of less than year

- Oestrogen-progesterone Treatment anterior in 3 months previous the inclusion

- Recently a viral Infection or bacteriologic(at least of 2 weeks)

- Dental Infection

- Inflammatory Pathology chronicles

- Antecedent of pathology cancerous with or no a sly hemopathy

- Addiction to smoking of more than 20 cigarettes a day or an alcoholic consumption

furthermore of 4 glasses a day

- Taken concomitant of one of the treatments forbidden: statine, vitamin B6 or B12,

folates, antiinflammatory, anti aggregant Plaquettes, DHEA, phytoestrogens

- Refusal to sign the assent informed

- Not membership in a regime about social security

CIC, Saint Antoine Hospital, Paris cedex 12 75571, France

Related publications:

Colditz GA, Willett WC, Stampfer MJ, Rosner B, Speizer FE, Hennekens CH. Menopause and the risk of coronary heart disease in women. N Engl J Med. 1987 Apr 30;316(18):1105-10.

Hodis HN, Mack WJ, Lobo RA, Shoupe D, Sevanian A, Mahrer PR, Selzer RH, Liu Cr CR, Liu Ch CH, Azen SP; Estrogen in the Prevention of Atherosclerosis Trial Research Group. Estrogen in the prevention of atherosclerosis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2001 Dec 4;135(11):939-53.

[No authors listed] Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA. 2002 Jul 17;288(3):321-33.

Mendelsohn ME, Karas RH. The protective effects of estrogen on the cardiovascular system. N Engl J Med. 1999 Jun 10;340(23):1801-11. Review. No abstract available.

Scarabin PY, Alhenc-Gelas M, Plu-Bureau G, Taisne P, Agher R, Aiach M. Effects of oral and transdermal estrogen/progesterone regimens on blood coagulation and fibrinolysis in postmenopausal women. A randomized controlled trial. Arterioscler Thromb Vasc Biol. 1997 Nov;17(11):3071-8.

Teede HJ, McGrath BP, Smolich JJ, Malan E, Kotsopoulos D, Liang YL, Peverill RE. Postmenopausal hormone replacement therapy increases coagulation activity and fibrinolysis. Arterioscler Thromb Vasc Biol. 2000 May;20(5):1404-9.

Conard J, Basdevant A, Thomas JL, Ochsenbein E, Denis C, Guyene TT, Degrelle H. Cardiovascular risk factors and combined estrogen-progestin replacement therapy: a placebo-controlled study with nomegestrol acetate and estradiol. Fertil Steril. 1995 Nov;64(5):957-62.

Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000 Mar 23;342(12):836-43.

Mallat Z, Heymes C, Ohan J, Faggin E, Leseche G, Tedgui A. Expression of interleukin-10 in advanced human atherosclerotic plaques: relation to inducible nitric oxide synthase expression and cell death. Arterioscler Thromb Vasc Biol. 1999 Mar;19(3):611-6.

Mallat Z, Hugel B, Ohan J, Leseche G, Freyssinet JM, Tedgui A. Shed membrane microparticles with procoagulant potential in human atherosclerotic plaques: a role for apoptosis in plaque thrombogenicity. Circulation. 1999 Jan 26;99(3):348-53.

Mallat Z, Benamer H, Hugel B, Benessiano J, Steg PG, Freyssinet JM, Tedgui A. Elevated levels of shed membrane microparticles with procoagulant potential in the peripheral circulating blood of patients with acute coronary syndromes. Circulation. 2000 Feb 29;101(8):841-3.

Ridker PM, Hennekens CH, Rifai N, Buring JE, Manson JE. Hormone replacement therapy and increased plasma concentration of C-reactive protein. Circulation. 1999 Aug 17;100(7):713-6.

Cushman M, Legault C, Barrett-Connor E, Stefanick ML, Kessler C, Judd HL, Sakkinen PA, Tracy RP. Effect of postmenopausal hormones on inflammation-sensitive proteins: the Postmenopausal Estrogen/Progestin Interventions (PEPI) Study. Circulation. 1999 Aug 17;100(7):717-22.

Scarabin PY, Alhenc-Gelas M, Oger E, Plu-Bureau G. Hormone replacement therapy and circulating ICAM-1 in postmenopausal women--a randomised controlled trial. Thromb Haemost. 1999 May;81(5):673-5.

van Baal WM, Smolders RG, van der Mooren MJ, Teerlink T, Kenemans P. Hormone replacement therapy and plasma homocysteine levels. Obstet Gynecol. 1999 Oct;94(4):485-91.

Starting date: March 2004
Ending date: January 2007
Last updated: January 16, 2008