Mavroudis K, Petsos P, Zulkifli Z, Cantrill J, Shingles C, Newman M, Mamtora H, Ratcliffe W A, Anderson D C
University of Manchester Department of Medicine, (Endocrinology), Hope Hospital, Salford, UK.
Gynecol Endocrinol. 1987 Jun;1(2):177-93. doi: 10.3109/09513598709030681.
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.
在开放性和双盲研究中，对40例长期不明原因不孕的女性进行了调查，并使用己酸17α-羟孕酮（17HPC，普洛孕酮长效注射剂）进行治疗。在开放性研究中，16例有高度可疑流产指标的女性每周肌肉注射（i.m.）500mg 17HPC，持续6 - 16周。其中6例女性在预期经期前开始用药；其中2例在该周期受孕且妊娠持续至足月，而4例未怀孕。10例女性（9例既往有明确流产史）在怀疑（正确）自己怀孕时使用了17HPC。除1例在34周早产（死产）外，其余所有女性的妊娠均持续至足月。在双盲研究中，24例女性从预期经期前约4天（-4天）开始，每周肌肉注射17HPC或安慰剂，前提是孕酮（Prog）水平（在-9至-7天）大于10nmol/l。使用安慰剂后，未观察到月经延迟或后续周期紊乱。在14例接受500mg 17HPC治疗的女性的16个周期中，有14个周期的撤药期延迟了几天，随后在接下来的1 - 3个月出现高度不规则出血。因此，剂量减至250mg 17HPC，但在16例女性的29个周期中有8个周期出现了同样的问题（包括上述在后续周期中研究的女性）。最终所有病例的月经周期均恢复正常，但有3例需要使用避孕药（妈富隆）进行治疗。在大多数治疗后的周期中，雌二醇（E2）呈进行性和持续性升高，血清促卵泡生成素（FSH）浓度或促黄体生成素/促卵泡生成素（LH/FSH）比值均无变化，且与预期的LH正反馈升高无关。我们得出结论，17HPC可能通过允许卵泡发育同时干扰LH正反馈来扰乱后续周期。双盲研究中的所有患者均未受孕（以无法检测到的人绒毛膜促性腺激素（hCG）水平为证）。我们的研究证实，这种孕激素没有直接的溶黄体作用。然而，为了确定在周期结束前给予17HPC的有效性，应选择高度怀疑反复早期着床失败或流产的女性。
