Long-acting contraception by monthly intramuscular injection is an attractive method for family planning which fills a gap in birth control technology. The main advantage of this approach over long-acting (2-6 months) progestin injectables is much better cycle control. To achieve this goal, an estrogen had to be included in the formulation with significant reduction in the progestin dose. Until 1976, there were only three monthly injectables available (Injectable No. 1, Cycloprovera and Deladroxate), but they were faced with logistic, toxicological or clinical problems. It took over 15 years to resolve many of these problems and add a new product (Mesigyna = 50 mg norethisterone enantate plus 5 mg estradiol valerate in an oily solution). Cycloprovera, at a lower dose, received the new name of Cyclofem and Deladroxate was manufactured under the trade names of Perlutal or Topasel. The latter requires in-depth re-evaluation of its toxicological hazards. There are many other formulations currently being developed with incomplete data so far on safety and efficacy.
PIP: The major advantage of once-a-month combined injectable contraceptives over long-acting progestin injectables is a considerably improved cycle control. Researchers added an estrogen while greatly reducing the progestin dose to achieve better cycle control. The only 3 monthly injectables available up to 1976 (Cycloprovera, Deladroxate, and Injectable No. 1) had logistical, toxicological, or clinical problems. Some of the toxicological problems for Deladroxate, for instance, included pituitary hyperplasia development in rats, a carry-over effect, and estradiol accumulation. Researchers resolved many of these problems over more than 15 years. Pharmacologists reduced the dose of Cycloprovera, which was then remarketed under the new name of Cyclofem. Since the original manufacturer withdrew Deladroxate from the market, other manufacturers now market it as Perlutal and Topasel. Researchers need to conduct a detailed reevaluation of the toxicological hazards of Deladroxate before it is approved for general use or is banned for its toxicity in humans. A new once-a-month combined injectable contraceptive has also been added, Mesigyna (50 mg norethisterone enanthate + 5 mg estradiol valerate in an oily solution consisting of castor oil and benzyl benzoate at a ratio of 6:4). Mesigyna performance is similar to that of Cyclofem. Monthly combined injectables with limited clinical experience include the trade names of Unimens and Lutofollin and 4 with various new combinations (e.g., 50 mg NET-EN and 5 mg estradiol unducelate). Four other products are at an early development stage.