HMG

• Approved / primary indications
• Ovulation induction in anovulatory women who have not responded to simpler measures (for example, clomiphene-resistant anovulation), including anovulation associated with polycystic ovary syndrome (PCOS) when appropriate.
• Controlled ovarian stimulation (COS) as part of assisted reproductive technologies (ART) such as in vitro fertilization (IVF) and intrauterine insemination (IUI) to promote the development of multiple follicles.
• Follicular development in women with hypogonadotropic hypogonadism who require exogenous gonadotropic support to achieve ovulation.
• Male indication
• Treatment of infertility in men with hypogonadotropic hypogonadism (in combination with human chorionic gonadotropin, hCG) to stimulate spermatogenesis and restore fertility.
• Important off-label / clinically accepted uses
• Use as part of specialized ovarian stimulation protocols tailored to poor responders or to specific clinic protocols where combined FSH/LH activity is preferred over recombinant FSH alone.
• Sequential or adjunctive use in select protocols where LH activity is clinically judged necessary for steroidogenesis and follicular maturation.

General principles: hMG products are formulated in International Units (IU) of gonadotropic activity (FSH and LH). Dose must be individualized according to indication, ovarian reserve, age, BMI, prior response and risk factors (e.g., PCOS). Strict clinical and ultrasonographic monitoring of follicular development and serum estradiol is required.

• Formulation & route
• Supplied as a powder for reconstitution or as pre-filled pens/vials for subcutaneous (SC) or intramuscular (IM) injection depending on product. Usual route: SC or IM; many clinics preferentially use SC. Use aseptic technique and appropriate needle length.
• Ovarian stimulation for IVF / COS (typical adult female dosing)
• Starting dose: commonly 75–300 IU daily (expressed as FSH activity equivalence) depending on ovarian reserve and patient factors.
• Standard protocols: daily injections for ~5–12 days with dose adjustments based on ultrasound and estradiol response; final maturation is triggered when follicles reach required size and estradiol criteria.
• Poor responders may require higher starting doses (e.g., up to 300 IU/day or individualized intensified regimens). Low responders / PCOS or high responders often warrant lower starting doses (e.g., 75 IU/day) to reduce risk of OHSS.
• Ovulation induction for anovulatory women (non-ART)
• Typical regimen: start with 75 IU daily or every-other-day regimens, adjust dose based on response; duration commonly 5–14 days until ovulation is achieved. Some clinicians use step-up or low-dose step-down strategies.
• If inadequate response after an appropriate interval, dosage can be incrementally increased (for example to 150 IU daily) under monitoring.
• Hypogonadotropic hypogonadism (women)
• Replacement / follicular development: individualized dosing often starting at 75–150 IU daily, adjusted to achieve follicular growth and ovulation.
• Male hypogonadotropic hypogonadism (to induce spermatogenesis)
• Typical combined regimen: pre-treatment or concurrent hCG to stimulate Leydig cells and testosterone production, plus hMG to provide FSH/LH activity for spermatogenesis.
• hMG dosing example: 75–150 IU three times weekly or 75 IU every other day (regimens vary) continued for several months (often 3–6 months or longer) until adequate spermatogenesis is achieved; therapy duration may be many months before semen improvement is seen. Adjustment depends on testosterone levels, testicular volume and semen analyses.
• Elderly
• hMG is not routinely used in post-reproductive elderly patients; no standard dosing—use only in specific fertility contexts.
• Renal / hepatic impairment
• No formal dose adjustment guidelines; as a protein biologic cleared by proteolytic pathways and reticuloendothelial system rather than renal CYP systems, routine dose modification is generally not required, but clinical data are limited. Use caution and clinical monitoring in severe organ dysfunction.
• Missed doses
• Administer as soon as practicable and continue per schedule; do not double doses. Adjustments may be needed based on monitoring.
• Special administration notes
• Reconstitute according to product instructions; if using pre-filled pens follow manufacturer technique. Rotate injection sites. Dispose of sharps safely.

Human menopausal gonadotrophin contains both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) bioactivity derived from human menopausal urine (or highly purified or recombinant preparations modeled on these activities). In females, FSH stimulates granulosa cell proliferation and follicular growth while LH (or LH activity) promotes theca cell androgen production and supports later stages of follicle maturation and ovulation. The combined FSH/LH activity increases estradiol synthesis by developing follicles and facilitates ovulation when a final maturation trigger is given. In hypogonadotropic men, exogenous FSH promotes Sertoli cell function and spermatogenesis while LH activity (or concurrent hCG which mimics LH) stimulates Leydig cells to produce testosterone—together restoring spermatogenesis and fertility.

• Absorption: After subcutaneous or intramuscular injection, gonadotropic proteins are absorbed into lymphatic and systemic circulation; time to peak concentrations varies with formulation and route.
• Distribution: As protein hormones, they distribute primarily in the extracellular compartment and act on gonadal receptors; they do not cross cell membranes freely.
• Metabolism: Clearance occurs by proteolytic degradation in the circulation and uptake and processing by the reticuloendothelial system and target tissues; there is no hepatic CYP-mediated metabolism typical of small molecules.
• Elimination: Fragments and amino acids are cleared by normal protein catabolic pathways; renal filtration of small peptides may occur but renal excretion of intact active hormone is not the primary elimination route.
• Half-life & duration: Biological activity persists sufficiently to permit once-daily or alternate-day dosing in many protocols; exact kinetic parameters vary by product (urinary-derived versus highly purified or recombinant-like preparations) and are influenced by formulation and patient factors.

• Pregnancy: hMG is contraindicated during pregnancy because its intended effect is to induce ovulation or follicular development; it is not to be used once pregnancy is established. Women should have a negative pregnancy test before initiating therapy and should avoid becoming pregnant during stimulation cycles until appropriate monitoring and timing of embryo transfer have been addressed in ART contexts. If pregnancy occurs, discontinue further doses.
• Lactation: Data on excretion into human milk are limited. hMG is not routinely administered postpartum for lactating women for fertility purposes; if use is clinically necessary, consider potential benefits and risks. Caution is advised due to limited safety data for breastfed infants.

• Primary therapeutic class: Gonadotropic hormone therapy (gonadotropins).
• Subclass: Menotropins / human menopausal gonadotrophin (hMG) — preparations providing combined FSH and LH activity (urinary-derived or highly purified menotropins).

• Known hypersensitivity to hMG or any component of the product.
• Primary ovarian failure (e.g., ovarian dysgenesis, ovarian failure) where uterus or ovaries are nonfunctional.
• Uncontrolled thyroid or adrenal dysfunction until these conditions are adequately treated.
• Ovarian cysts or enlargement of undetermined origin (unless monitored and judged appropriate).
• Pregnancy and breastfeeding when pregnancy is established.
• Sex hormone-dependent tumors (e.g., known or suspected estrogen-dependent neoplasia).
• Severe uncontrolled systemic disease that precludes therapy or pregnancy.

• Ovarian hyperstimulation syndrome (OHSS): A potentially serious complication characterized by enlarged ovaries, abdominal pain, ascites, hemoconcentration, and in severe cases pleural effusion, thromboembolism and renal impairment. Risk factors include young age, low BMI, polycystic ovarian morphology, high ovarian reserve, high estradiol levels and rapid multiple follicle growth. Immediate cessation of stimulation and specialized management may be required with moderate-to-severe OHSS.
• Multiple pregnancy: Therapy increases the risk of multiple gestation (twins, triplets), which carries higher maternal and fetal risks. Counsel patients on the risk and consider single embryo transfer policies in ART settings where applicable.
• Thromboembolic events: Rarely associated with ovarian stimulation; monitor for signs of venous thromboembolism, particularly in patients with predisposing risk factors.
• Monitoring requirements: Frequent transvaginal ultrasound assessment of follicular development and serial serum estradiol measurements are essential to guide dose adjustments and reduce risks.
• Psychological effects: Emotional lability and mood changes may occur in the fertility treatment context; provide counseling and support.
• Visual disturbances / sudden abdominal pain: May indicate ovarian torsion, rupture, or severe OHSS—seek urgent assessment.
• Use in PCOS: Start with lower doses and escalate cautiously to reduce OHSS risk.
• Use in men: Long duration of therapy (months) may be required before spermatogenesis is adequate; monitor semen parameters and endocrine markers.

• Very common / common
• Local injection site reactions: pain, erythema, swelling, bruising.
• Systemic: fatigue, headache, nausea, breast tenderness, abdominal discomfort or bloating.
• Important / less common
• Ovarian hyperstimulation syndrome (OHSS): ranges from mild abdominal discomfort to severe life-threatening forms with ascites, hemoconcentration and thromboembolism.
• Multiple pregnancy with associated obstetric risks.
• Ovarian enlargement, ovarian cyst formation.
• Rare / serious
• Thromboembolic events (deep vein thrombosis, pulmonary embolism) in severe OHSS.
• Ovarian torsion or rupture—surgical emergencies.
• Allergic reactions including anaphylaxis (rare).
• Long-term safety: pregnancy outcomes and fetal safety are well-studied in ART populations; however, fertility treatments carry inherent obstetric risks that require specialist management.

Timing & dose-dependence: Local and systemic mild effects typically occur within hours to days after injection and are dose-dependent (higher doses and aggressive stimulation increase risk of OHSS and multiple follicles). Serious complications are related to excessive ovarian response rather than immediate dose reactions.

• Concomitant use with GnRH agonists or antagonists: Commonly used in ART protocols; interactions are pharmacodynamic and intentionally exploited to control endogenous gonadotropin release. Protocol selection (agonist vs antagonist) affects timing and dosing and must be coordinated by the treating clinician.
• Co-administration with hCG: hCG is frequently used as a trigger for final oocyte maturation; when used therapeutically in men, hCG replaces LH activity—coordinate dosing with hMG in male hypogonadotropic hypogonadism.
• No clinically relevant metabolic drug-drug interactions mediated by hepatic enzymes (CYP450) are expected because hMG is a protein biologic cleared via proteolysis rather than hepatic small-molecule pathways.
• Drug-food / drug-alcohol interactions: None identified of clinical relevance; lifestyle factors affecting OHSS risk (e.g., dehydration) should be managed.

• Individualized dosing strategies and ovarian reserve assessment (AMH, antral follicle count) are increasingly emphasized to tailor starting doses and minimize OHSS and multiple pregnancy risk.
• Antagonist protocols and ‘freeze-all’ strategies are commonly used to reduce OHSS risk in high responders; elective single embryo transfer policies aim to reduce multiple gestations following stimulation.
• Use of highly purified menotropin preparations and pen devices has improved dosing accuracy and reduced injection-site issues compared with older crude preparations.
• Male infertility protocols emphasize combined gonadotropin/hCG regimens for hypogonadotropic hypogonadism, recognizing that months of therapy are typically required for meaningful spermatogenic response.
• National and society guidelines recommend close monitoring, patient counseling about OHSS and multiple pregnancy risks, and individualized protocols based on ovarian reserve testing.

• Temperature: Store lyophilized powder or reconstituted products refrigerated at 2°C to 8°C unless product-specific labeling provides alternate instructions. Do not freeze.
• Light & humidity: Keep in original packaging to protect from light and moisture.
• Reconstitution & handling: Reconstitute with supplied diluent exactly per product instructions; use reconstituted solution within the timeframe specified by the manufacturer (varies by product: some allow same-day or short-term use). Do not use if solution is discolored or contains particulate matter; discard opened or unused reconstituted product according to local protocols and manufacturer guidance.
• Transport & field handling: Maintain cold chain during transport. For pen or liquid formulations, adhere to manufacturer shelf-life and in-use stability statements.