The pharmacology and clinical assessment of existing first generation once-a-month combined
injectable contraceptives, mainly
Deladroxate and
Chinese Injectable No. 1, are reviewed. Although these two types of monthly
injectables have been used in some million women in China and Latin America,
Deladroxate needs indepth re-evaluation of its long-term toxicity and possible accumulation. For
injectable No. 1, its disadvantage of being administered on an erratic schedule will cause significant
confusion in family planning practice. When used in a strict once-a-month schedule, it is not sufficiently effective for
contraception. In order to attain predictable menstrual cycle control as well as high efficacy with a 30-day injection schedule, two improved once-a-month
injectable formulations,
Cyclofem and
Mesigyna, were developed. Pharmacokinetic/pharmacodynamic study on estrogenic components suggested that
estradiol valerate and cypionate were suitable
estrogen esters to give elevated plasma
estrogen levels for 7 to 11 days. After a single injection of
Cyclofem and
Mesigyna, both formulations showed equal
contraceptive effect with inhibition of follicle maturation for some 30 days and ovulation, corpus luteum formation for some 60 days. Multicentre studies on the optimization of dosages of
progestogens and
estrogens in once-a-month
injectables confirmed that the full doses of
Cyclofem (
DMPA 25 mg/
estradiol cypionate 5 mg) and
Mesigyna (NET-EN 50 mg/
estradiol valerate 5 mg) are suitable for large scale clinical trials. Pharmacodynamics and
progestogen/
estrogen ratio study indicated the importance of not only the absolute amounts of the
progestogen and
estrogen but also of their ratio. Reduction of
estrogen dose resulted in breakthrough ovulation with both
Cyclofem and
Mesigyna. Also, it is important to note that the second part of the injection cycle is dominated by the
progestogen component of both monthly formulations. A longitudinal study indicated that there is no accumulation of
norethisterone after 12 months of treatment with NET-EN 50 mg and
estradiol valerate 5 mg.