Role of progestins with partial antiandrogenic effects.

An experts' meeting on the 'Role of progestins with partial antiandrogenic effects' was held in Berlin from January 19 to 22, 2001. The meeting was chaired by Dr R. Sitruk-Ware (New York, USA) and participants included Ms F. Fruzzetti (Pisa, Italy), J. Hanker (Trier, Germany), J. Huber (Vienna, Austria), F. Husmann (Bad Sassendorf, Germany), S. O. Skouby (Copenhagen, Denmark), J. H. H. Thijssen (Utrecht, The Netherlands), and R. Druckmann (Nice, France). The present paper reports the conclusions of the meeting. However, the publication of the Women's Health Initiative study, which appeared after the meeting, led to additional comments and revisions.

[Is primary, secondary or tertiary prevention of coronary heart disease possible by means of oestrogens or gestagens?]. / Ist eine Primär-, Sekundär- oder Tertiärprävention der koronaren Herzerkrankung durch Estrogene und Gestagene möglich?

Clinical trials in primary prevention of coronary atherosclerosis have demonstrated that estrogen application in postmenopausal women may reduce the relative risk by approximately 50 % when initiated at the time of decreasing endogenous estradiol production. Multifactorial estrogen actions (i. e. vasodilatation, inhibition of vascular smooth muscle cell proliferation) could explain these observations. Based on some investigations in secondary and tertiary prevention of coronary atherosclerosis in postmenopausal women it may be concluded that oestrogens alone or in combination with certain progestins may have a protective effect in reducing the rate of reinfarctions. From an epidemiological point of view it was emphasized that these studies were not randomised and therefore not suitable for drawing conclusions generally valid in all postmenopausal women. The HERS-study was initiated in order to get reliable informations. However, the results of this study are not comparable with any other investigation as in the HERS-study for the first time a continuous combined oestrogen/progestin application was chosen. The authors pointed out that several positive oestrogen actions may be antagonised by progestins as the oestrogen receptor density could be down regulated by progestins. The HERS study shows indeed no increase in reinfarctions and a decrease in total mortality after long term treatment. Consequently, the study shows that there is a demand to strongly emphasise the significance of primary prevention.

[Secondary and tertiary prevention of atherosclerotic vessel disease]. / Sekundär- und Tertiärprävention arteriosklerotischer Gefässerkrankungen.

A first randomized, prospective, placebo-controlled, blind study--the so called HERS-Study--was designed to demonstrate that continuously combined application of 0.625 mg conjugated estrogens and 2.5 mg medroxyprogesterone acetate is a suitable treatment regimen in secondary and tertiary prevention of coronary artery atherosclerotic disease. After a 4.1 years duration of treatment no essential differences in the occurrence of reinfaction, other complications due to atherosclerotic alterations, and survival rates between verum and placebo groups could be evaluated. Unanswered ist, whether the duration of treatment was sufficiently long, the dose of estrogens high enough, or whether the mechanism of estrogen action is antagonized at least in part by continuously administered medoxyprogesterone acetate. Several other questions remain open due to scanty informations on LDL-concentrations, and a complete lack of data concerning insulin/insulin resistance, hyperglycemia, respectively. Better results may be obtained with sequential estrogen/progestin treatment regimes or with estrogens only, progestins added on demand. Remaining additional risk factors have to be treated. Life style and nutritional habits should be adapted to atherosclerosis.

[Clinical experiences with Climen in peri- and postmenopausal women]. / Klinische Erfahrungen mit Climen bei peri- und postmenopausalen Frauen.

42 women with signs of androgenization were treated with Climen in the peri- and postmenopause for a period longer than 12 months. The effect on most typical climacteric syndromes was comparable to other free available compounds. Concerning our patients, Climen was more effective than other compounds. In no case the withdrawal of Climen due to side-effects was necessary. Surprisingly an androgenetical loss of hair was stopped in 9 out of 10 cases. Climen widens essentially the therapeutical possibilities concerning hormone replacement in peri- and postmenopausal women and should not only be used in women with signs of androgenization.

[Interaction problems in the therapy with steroid-free anti-rheumatics]. / Interaktionsprobleme bei der Therapie mit steroidfreien Antirheumatika.

In a review the known interactions between non-steroidal antirheumatic drugs and others are summarized. Of clinical importance are interactions with digitalis, anticoagulants, oral antidiabetics, beta receptor antagonists, antihypertensive drugs, and diuretics. Interactions may occur if uricosurics or anticonvulsive drugs are administered together with non-steroidal antirheumatic drugs. Interactions are observed between different antirheumatic drugs when administered together. Undesirable side effects induced by drug interactions can be avoided by means of administration of suitable drugs in those cases in which a combined treatment is necessary.