HMG Dosage Chart, Schedule & Reconstitution Protocol

Mechanism of Action (MOA)

Human menopausal gonadotropin (hMG, menotropins) is a purified preparation of pituitary gonadotropins extracted from the urine of postmenopausal women, in whom elevated circulating FSH and LH (due to loss of ovarian negative feedback) result in concentrated gonadotropin excretion. Modern preparations such as Menopur are highly purified to minimize urinary protein contaminants and standardized to deliver approximately 75 IU of FSH bioactivity and 75 IU of LH bioactivity per vial (typically a 1:1 ratio), with LH activity supplied predominantly by hCG present in postmenopausal urine. Bravelle, by contrast, contains highly purified urinary FSH without LH activity, while recombinant FSH preparations (Gonal-F, Follistim, Puregon) provide pure FSH from CHO cell production [1]. In women, controlled ovarian stimulation for in vitro fertilization (IVF) and other assisted reproductive procedures aims to recruit multiple follicles for retrieval. FSH binds the FSH receptor on granulosa cells of antral follicles, driving follicular growth, granulosa cell proliferation, and aromatase expression for conversion of theca-cell-derived androgens into estradiol. LH, supplied by the hMG component, acts on theca cells to stimulate androgen synthesis (providing the aromatase substrate) and on granulosa cells of larger preovulatory follicles to support final oocyte maturation. The balance between FSH and LH is clinically relevant: pure FSH may be insufficient in older patients and those with severely suppressed endogenous LH, while combined FSH/LH (hMG) is often preferred in long agonist protocols and in patients with diminished ovarian reserve [2]. Standard hMG protocols for IVF initiate at 75–225 IU subcutaneously daily, with dose adjustments every two days based on serial transvaginal ultrasound and serum estradiol monitoring. Maximum doses generally do not exceed 450 IU/day, and treatment duration rarely extends beyond twelve days. Once follicles reach 17–18 mm diameter, ovulation is triggered with hCG (5,000–10,000 IU IM) or a GnRH agonist, followed by oocyte retrieval 34–36 hours later. For anovulatory women without IVF, lower hMG doses (75–150 IU/day) are used with monitoring to develop a single dominant follicle and avoid multiple gestation [3]. In men, hMG combined with hCG is the standard combined gonadotropin protocol for induction of spermatogenesis in hypogonadotropic hypogonadism (Kallmann syndrome, idiopathic HH, post-pituitary surgery, and acquired GnRH deficiency). hCG (1,000–2,500 IU two to three times weekly) provides LH activity to stimulate Leydig cell testosterone production and intratesticular androgen levels, while hMG (75–150 IU three times weekly) provides FSH activity to drive Sertoli cell function and spermatogenesis. Spermatogenesis develops over 6–24 months with response rates of 70–90 percent in carefully selected populations [4]. In off-label post-cycle therapy contexts, some practitioners use hMG alongside hCG and SERMs to restore HPG axis function after anabolic-androgenic steroid use, on the theoretical basis that exogenous androgens suppress both LH and FSH, leaving both Leydig and Sertoli cell function impaired. Typical PCT-adjunctive hMG dosing is 75–150 IU two to three times weekly for two to four weeks, although controlled clinical evidence supporting this practice is limited and most PCT protocols rely on hCG plus SERMs without additional FSH. Pharmacokinetically, urinary-derived hMG has a longer effective duration than recombinant FSH because of glycosylation pattern differences, allowing every-other-day dosing in some protocols [5].