Steroidale kontrazeptiva

In particular, the provision of a dissociated progestin with an antiproliferative potential in the breast tissue and, at the same time, beneficial effects in the endometrium seems desirable, as there is a number of epidemiological studies about the relation between breast cancer incidence and use of combined oral contraceptives (COCs) or HRT, especially with respect to extended periods of use (see ., . Malone et al., Epidemiologic Reviews 1993, 15, 80-97 and Standford et al., Epidemiologic Reviews 1993, 1 S, 98-107). Although the risks are contradictory and controversial, there is evidence that many years of intake under certain circumstances might enhance the mitotic activity of normal breast epithelial cells. Therefore, a dissociated activity profile of progestins regarding the provision of beneficial, . antiproliferative, effects in the breast, but with the classical progestagenic effects in the ovary and/or uterus is desirable.
Recently, assays for screening for progesterone receptor ligands exhibiting tissue-specificity have been provided, cf. WO 02/054064. One approach of screening for progesterone receptor (PR) ligands with a dissociated activity profile was based on the fact that the PR is expressed in two different isoforms (PR-A and PR-B) which seem to be capable of being activated independently of each other by compounds having a selectivity for either PR-A or PR-B.
Both PR-isoforms are expressed in all progesterone target organs tested so far (.
breast, uterus). However, there is strong evidence that PR-A and PR-B function in a tissue-specific manner to mediate responses to progesterone. Isoform-specific knock-out mice show different functions of PR-A and PR-B in the same target organ. Based on these studies, PR-B seems to be the most responsible receptor for mammary gland proliferation and differentiation, whereas the antiproliferative action of progestins on the uterine epithelium and on ovulation is most likely mediated by PR-A (B. Mulac-Jericevic, Science 2000, 289, 1751-1754; Orla Conneely, Endocrine Society Meeting, Toronto, June 2000).

Schwere allergische Reaktionen (Hautausschlag, Nesselsucht, Juckreiz, Atembeschwerden, Engegefühl in der Brust, Schwellungen im Mund-, Gesichts-, Lippen oder Zunge), schwarz, Teerstühle, Änderungen in der Menstruation, Brustschmerzen, Augenschmerzen oder erhöhtem Druck in das Auge, Fieber, Schüttelfrost oder Halsschmerzen, Gelenk-oder Knochenschmerzen; Stimmung oder psychische Veränderungen (zB Depression), Muskelschmerzen oder Schwäche, Krampfanfälle, schwere oder anhaltende Kopfschmerzen, schweren oder anhaltenden Übelkeit oder Erbrechen, Bauchschmerzen oder Blähungen; Anschwellen der Füße oder Beine, Schlafstörungen, ungewöhnliche Gewichtszunahme oder-verlust, Sehstörungen, Erbrechen Material, das aussieht wie Kaffeesatz.

987 women aged 18-45 were screened for ALAT, ASAT, and liver size to detect liver damage among users and nonusers of oral contraceptives (OCs). 36 (%) of them showed liver symptoms. 174 women of the same caseload were examined in a follow-up; 57 dropped out. 116 women aged 19-50 remained, 54 nonusers and 62 OC users. 9 women were classed as having liver disease, and 107 were classed as having healthy livers. In the whole sample, daily consumption of alcohol averaged + or - gm. Side effects included spotting (50 cases), epigastric complaints (10 cases), brown skin spots (3 cases), and migraine headache (18 cases). 2 OC users who had liver symptoms had systolic blood pressure >180 mm Hg and diastolic pressure of 120 mm Hg. 38 women were also taking other medication. Those with liver disease deviated more from the optimum body weight as measured by the Mohr and Johnsen form. Healthy women had a liver size of + or - cm, while those with liver disease had a + or - cm sized liver. 8 of the women with liver disease showed higher gamma-GT (glutamic transferase) activity compared to healthy women. According to these findings, there is no connection between OC use and liver damage as determined by aminotransferase activity. Therefore, the determination of ALAT activity for OC users is superfluous, and it could save a lot money if this test were discontinued as presently practiced during the annual gynecological examination of OC users.

Steroidale kontrazeptiva

steroidale kontrazeptiva

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