Trial of 17-hydroxyprogesterone caproate (Proluton Depot) in women with long-standing infertility; failure of estrogen positive feedback the following cycle.
In open and double-blind studies 40 women with long-standing unexplained infertility were investigated and treated with 17 alpha-hydroxyprogesterone caproate (17HPC, Proluton Depot). In the open study, 16 women with a high index of suspicious abortions were given 500 mg 17HPC imtramuscularly (i.m.) weekly for 6-16 weeks. Six of the women received the drug from a time preceding the expected date of a period; 2 of these conceived that cycle and their pregnancies continued to term, while 4 were not pregnant. Ten women (9 with definite previous abortions) were given 17HPC when they suspected (correctly) that they were pregnant. Their pregnancies continued to term in all but 1, who had a premature delivery (still-birth) at 34 weeks. In the double-blind study 24 women were given injections of 17HPC or placebo i.m. at weekly intervals, from about 4 days before the expected period (day -4), provided that the level of progesterone (Prog) (on days -9 to -7) was greater than 10 nmol/l. After placebo no delay in menstruation or disruption of the succeeding cycle was observed. In 14 of 16 cycles in 14 women given 500 mg 17HPC the withdrawal period was delayed by a few days, and then followed by highly erratic bleeding over the next 1-3 months. The dose was therefore reduced to 250 mg 17HPC but the same problem resulted in 8 of 29 cycles in 16 women (including the above studied in later cycles). Regular cycles were eventually restored in all cases but in 3 this necessitated treatment with the contraceptive pill (Microgynon). In most of the post-treatment cycles there was a progressive and prolonged estradiol (E2) rise, which was not preceded by changes either in serum FSH concentration or in the LH/FSH ratio nor associated with the expected positive feedback rise in LH. We conclude that 17HPC disrupts the following cycle, probably by allowing follicular development while interfering with positive LH feedback. None of the patients of the double-blind study had conceived (as evidenced by undetectable hCG levels). Our study confirmed that this progestogen exerts no direct luteolytic effect. However, in order to establish the efficacy or otherwise of 17HPC given before the end of the cycle, women should be selected with a very high index of suspicion of recurrent early implantation failure or abortion.