What are human menotropins (hormone replacement therapy)?

What Are Human Menotropins?

Human menotropins are urinary-derived gonadotropin preparations extracted from the urine of postmenopausal women, containing both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) activity, used primarily for ovulation induction in infertile anovulatory women who have failed clomiphene citrate therapy. 1

Composition and Source

• Menotropins contain approximately equal amounts of FSH and LH activity (typically 75 IU FSH and 75 IU LH per ampoule), along with small amounts of human chorionic gonadotropin (hCG). 2, 3
• The product is extracted and purified from urine collected from postmenopausal women, who naturally excrete high levels of pituitary gonadotropins. 4, 5
• Also known as human menopausal gonadotropin (HMG), this represents one of the earliest fertility treatments developed, with nearly four decades of clinical use. 4, 5

FDA-Approved Indications

The FDA label specifies three primary indications for menotropins 1:

• Induction of ovulation and pregnancy in anovulatory, infertile women where anovulation is secondary (not due to primary ovarian failure) and who have been appropriately pretreated with human menotropins
• Treatment of prepubertal cryptorchidism not due to anatomical obstruction (when used with hCG)
• Selected cases of hypogonadotropic hypogonadism in males (when used with hCG)

Clinical Context: When Menotropins Are Used

Menotropins are indicated specifically for WHO type II anovulation (typically polycystic ovary syndrome) when clomiphene citrate has failed. 6

• For normogonadotropic women undergoing assisted reproductive technologies with GnRH agonist suppression, menotropins offer advantages over pure FSH preparations. 3
• In hypogonadotropic hypogonadism (WHO type I anovulation), exogenous LH supply is required for adequate follicular response, making menotropins the preferred choice over pure FSH. 6, 4

Clinical Advantages of LH Activity in Menotropins

Recent evidence demonstrates specific benefits of the LH component 3:

• Shorter treatment duration (12.6 vs 16.1 days) compared to highly purified FSH alone 3
• Lower total gonadotropin consumption (23.6 vs 33.6 ampoules per cycle) 3
• Reduced development of small follicles (<10 mm) in the late follicular phase 3
• Higher estradiol levels during stimulation, though this may increase ovarian hyperstimulation syndrome (OHSS) risk 2, 3

Critical Safety Warnings

The FDA label emphasizes that menotropins must only be used by physicians experienced with infertility problems 1:

Principal serious adverse reactions include:

• Ovarian hyperstimulation syndrome (sudden ovarian enlargement, ascites with or without pain, pleural effusion) 1
• Rupture of ovarian cysts with resultant hemoperitoneum 1
• Multiple births 1
• Arterial thromboembolism 1
• Anaphylaxis and hypersensitivity reactions with urinary-derived products 1

Important Clinical Caveats

• When serum LH concentration during midfollicular phase is 0.5-1.5 IU/L in long GnRH-agonist protocols, adding menotropins may decrease fertilization rates (69.6% vs 89.1%) and increase OHSS risk. 2
• In normogonadotropic women with adequate endogenous LH, pure FSH preparations may be preferable to avoid overstimulation. 2, 4
• Menotropins are comparably effective to highly purified FSH preparations in terms of pregnancy outcomes, though recombinant FSH may offer superior batch-to-batch consistency. 6, 4

Comparison with Modern Alternatives

• Recombinant FSH preparations offer superior purity and consistency but are more expensive than urinary-derived menotropins. 6, 4
• If cost is a consideration and availability is not an issue, menotropins remain a valid option for ovulation induction. 6
• For women requiring LH activity (hypogonadotropic hypogonadism), menotropins provide both FSH and LH in a single preparation. 6, 4

Administration Protocol

• Menotropins require careful dose titration using a chronic low-dose protocol with small increments to minimize multiple follicular development and OHSS risk. 6
• Treatment must be monitored with serial ultrasound and hormonal assessments (estradiol, LH, progesterone). 3
• hCG is administered separately to trigger final oocyte maturation once adequate follicular development is achieved. 1, 3