Depot gestagens
Zahradnik, H.P.
Archives of Gynecology and Obstetrics 257(1-4): 536-541
1995
ISSN/ISBN: 0932-0067 PMID: 8579439 DOI: 10.1007/bf02264884Document Number: 298298
Depot-medroxyprogesterone acetate (DMPA) in a dose of 1-2 g per injection has been administered up to 3 times a week i.m. since the early 1960s for the prevention of miscarriage, but this therapy has proven unsuccessful. However, its use for contraception proved effective. Depot-norethindrone enanthate (NET-EN) was combined with DMPA in the late 1960s. NET-EN was injected every two months. In Germany, DMPA preparations made by the Upjohn Co. (Depot-Clinovir) and NET-EN made by the Schering Co. (Noristerat) are available for contraceptive purposes. Injectable gestagens are used in more than 80 countries worldwide, except for the US, because in studies on beagle dogs breast tumors developed. Injectables occupy a high share of contraceptives in developing countries: 8% in Kenya, 12% in Thailand, and almost 20% in Jamaica, while in central Europe the three-month injectable represents only 1% of contraceptive agents. In terms of pharmacokinetics, the maximum concentration of NET-EN is reached after an injection of 1 mg/kg i.m., averaging 2-5 ng/ml, which is over the 1 ng/ml dose required for contraceptive effectiveness. The bioavailability is 100% when so applied, while the elimination half-time is 15-20 days. A 1977 WHO study revealed a continuation rate of 70-75% after 12 months. About 10% complained of bleeding disorders. Within the first 6 months of DMPA use amenorrhea sets in in one-third of the cases; it occurs in over 60% of cases after 1-1.5 years of use. Bleeding disorders often cause discontinuation, which can be treated with estrogen-gestagen combination preparations. Dihydroxyprogesterone acetophenid is combined with estradiol enanthate (E2-EN), MPA with estradiol cypionate (E2-Cyp), NET-EN with estradiol valerate (E2-Val), and 17-alpha-hydroxyprogesterone caproate with E2-Val. The rate of continuation with the DMPA/estrogen combination was more than 60%, while it varied between 26.5% and 44.1% with NET-EN plus E2-Val after 1 year of use.