Shoham Z, Mannaerts B, Insler V, Coelingh-Bennink H
Department of Obstetrics and Gynecology, Kaplan Hospital, Rehovot, Israel.
Fertil Steril. 1993 Apr;59(4):738-42. doi: 10.1016/s0015-0282(16)55852-x.
To examine the safety, tolerance, pharmacokinetics, follicular growth, and steroidogenesis after the administration of recombinant human FSH (Org 32489; Organon International, Oss, The Netherlands) in women with isolated hypogonadotropic hypogonadism.
An open phase I multiple rising dose study with recombinant FSH in two hypogonadotropic but otherwise healthy women. The drug was administered intramuscularly one time per day for a maximum of 21 days, i.e., 75 IU for the first 7 days, 150 IU for the next 7 days, and 225 IU during the last 7 days. Treatment was discontinued if serum E2 was > or = 1,100 pmol/L and/or one or more growing follicle > 14 mm in diameter was observed. After the last recombinant FSH injection, subjects were monitored for another 3 weeks.
Specialist Reproductive Endocrinology and Infertility Unit.
Two women with isolated hypogonadotropic hypogonadism who did not want to get pregnant anymore.
Serum FSH, androstenedione (A), T, P, LH, follicular growth, and endometrial thickness. Safety parameters: blood pressure, heart rate, urinalysis, hematology, blood biochemistry, and antirecombinant FSH antibodies.
Treatment with recombinant FSH resulted in dose-related increases of serum FSH. Both women showed follicular growth (diameter, 17 mm), whereas serum A concentrations were very low, and serum E2 concentrations rose to only 76.7 and 139.5 pmol/L, respectively. No antirecombinant FSH antibody formation or changes of safety variables were noted.
This study in two women with hypogonadotropic hypogonadism is consistent with the two-cell theory that FSH alone can induce follicular growth. The low concentrations of A and E2 indicate the need for LH to induce appropriate steroidogenesis. It was also found that recombinant FSH is well absorbed, safe, and well tolerated after daily treatment for up to 21 days.
研究重组人促卵泡激素（Org 32489；荷兰欧加农国际公司，奥斯）用于单纯性低促性腺激素性性腺功能减退女性后的安全性、耐受性、药代动力学、卵泡生长及甾体激素生成情况。
一项开放性I期多剂量递增研究，对两名低促性腺激素但其他方面健康的女性使用重组促卵泡激素。药物每天肌内注射1次，最多注射21天，即前7天每天注射75 IU，接下来7天每天注射150 IU，最后7天每天注射225 IU。若血清雌二醇（E2）≥1100 pmol/L和/或观察到一个或多个直径>14 mm的生长卵泡，则停止治疗。最后一次注射重组促卵泡激素后，对受试者再监测3周。
生殖内分泌与不育专科单位。
两名不再希望怀孕的单纯性低促性腺激素性性腺功能减退女性。
血清促卵泡激素（FSH）、雄烯二酮（A）、睾酮（T）、孕酮（P）、促黄体生成素（LH）、卵泡生长及子宫内膜厚度。安全性参数：血压、心率、尿液分析、血液学、血液生化及抗重组促卵泡激素抗体。
重组促卵泡激素治疗导致血清FSH呈剂量依赖性升高。两名女性均出现卵泡生长（直径17 mm），而血清A浓度很低，血清E2浓度分别仅升至76.7和139.5 pmol/L。未观察到抗重组促卵泡激素抗体形成或安全性变量改变。
对两名低促性腺激素性性腺功能减退女性的这项研究结果符合双细胞理论，即单独使用促卵泡激素即可诱导卵泡生长。A和E2浓度较低表明需要促黄体生成素诱导适当的甾体激素生成。还发现重组促卵泡激素在每日治疗长达21天后吸收良好、安全且耐受性良好。
