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Menotropins

Pronunciation

(men oh TROE pins)

Index Terms

  • hMG
  • Human Menopausal Gonadotropin

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injection, powder for reconstitution:

Menopur: 75 units [supplied with diluent]

Repronex: 75 units [supplied with diluent]

Brand Names: U.S.

  • Menopur
  • Repronex

Pharmacologic Category

  • Gonadotropin
  • Ovulation Stimulator

Pharmacology

Menotropins is a purified combination of follicle stimulating hormone (FSH) and luteinizing hormone (LH) extracted from the urine of postmenopausal women. Treatment provides ovarian follicular growth and maturation in females who do not have primary ovarian failure. Also stimulates spermatogenesis in males (off-label use)

Excretion

Urine

Time to Peak

FSH (following a single dose): Menopur: 18 hours (SubQ); Repronex: 12 hours (SubQ), 18 hours (IM)

Half-Life Elimination

Menopur: FSH 11-13 hours (following multiple doses)

Repronex: FSH ~54-59 hours (following a single dose)

Use: Labeled Indications

Menopur: For multiple follicle development and pregnancy in ovulatory women as part of an assisted reproductive technology (ART) cycle

Repronex: In conjunction with hCG to for multiple follicular development (controlled ovarian stimulation) and ovulation induction in women who have previously received GnRH agonist or antagonist for pituitary suppression

Limitations of use: Prior to therapy, preform a complete gynecologic exam and endocrinologic evaluation to diagnose the cause of infertility; exclude the possibility of pregnancy; evaluate the fertility status of the male partner; exclude a diagnosis of primary ovarian failure.

Use: Unlabeled

Male: Stimulation of spermatogenesis in primary or secondary hypogonadotropic hypogonadism

Contraindications

Hypersensitivity to menotropins or any component of the formulation; primary ovarian failure as indicated by a high follicle-stimulating hormone (FSH) level; uncontrolled nongonadal endocrinopathies (eg, thyroid, adrenal, pituitary); pituitary or hypothalamic tumors; abnormal uterine bleeding of undetermined origin; ovarian cyst or enlargement not due to polycystic ovary syndrome; pregnancy

Menopur is also contraindicated with sex hormone-dependent tumors of the reproductive tract and accessory organs.

Repronex is also contraindicated with infertility due to any cause other than anovulation (except candidates for in vitro fertilization).

Dosing: Adult

Ovulation induction (females): Repronex: IM, SubQ: Initial: 150 units once daily for the first 5 days of treatment. Adjustments should not be made more frequently than once every 2 days and should not exceed 75-150 units per adjustment based on ultrasound monitoring of ovarian response and/or measurement of serum estradiol levels. Maximum daily dose: 450 units; treatment >12 days is not recommended. If patient's response is appropriate, administer hCG one day following the last dose of Repronex. Hold dose if serum estradiol is >2000 pg/mL, if the ovaries are abnormally enlarged, or if abdominal pain occurs; the patient should also be advised to refrain from intercourse. May repeat process if follicular development is inadequate or if pregnancy does not occur.

Assisted reproductive technologies (ART) (females):

Menopur: SubQ: Initial: 225 units once daily beginning on cycle day 2 or 3; Menotropins may be administered together with urofollitropin and the total initial dose of both products combined should not exceed 225 units (menotropins 150 units and urofollitropin 75 units; or menotropins 75 units and urofollitropin 150 units). Dose should be adjusted after 5 days based on ultrasound monitoring of ovarian response and/or measurement of serum estradiol levels. Do not make additional adjustments more frequently than once every 2 days or by >150 units. Maximum daily dose: 450 units (of menotropins, or menotropins plus urofollitropin); treatment >20 days is not recommended. Once adequate follicular development is evident, hCG should be administered. Withhold the hCG dose if ovarian monitoring suggests an increased risk of ovarian hyperstimulation syndrome (OHSS).

Repronex: IM, SubQ: Initial: 225 units once daily; adjustments in dose based on ultrasound monitoring of ovarian response and/or measurement of serum estradiol levels should not be made more frequently than once every 2 days and should not exceed more than 75-150 units per adjustment. Maximum daily dose: 450 units; treatment >12 days is not recommended. Once adequate follicular development is evident, hCG should be administered to induce final follicular maturation in preparation for oocyte retrieval. Withhold the hCG dose if ovarian monitoring suggests an increased risk of OHSS.

Spermatogenesis (males) (off-label use): IM: Following pretreatment with hCG: 75 units 3 times per week with hCG twice weekly until sperm is detected in the ejaculate (4-6 months); if response is inadequate after 6 months, may increase menotropins dosage to 150 units 3 times per week for another 6 months (AACE, 2002)

Dosing: Renal Impairment

There are no dosage adjustments provided in manufacturer’s labeling (has not been studied).

Dosing: Hepatic Impairment

There are no dosage adjustments provided in manufacturer’s labeling (has not been studied).

Reconstitution

Menopur: Reconstitute with sodium chloride 0.9% for injection (provided); gently swirl to dissolve, do not shake to avoid formation of bubbles. Use immediately after reconstitution. May also be mixed with Bravelle (urofollitropin for injection).

Repronex: Reconstitute with sodium chloride 0.9% injection (provided).

If more than 1 vial of menotropins is required for a single dose, up to 6 vials can be reconstituted and administered as a single injection. This is done by first reconstituting 1 vial with sodium chloride 0.9% injection as previously described, withdrawing the entire contents of the reconstituted vial, and (using this as the diluent for the second vial) injecting into the second vial, etc. Use immediately after reconstitution.

After reconstitution inject immediately; discard any unused portion.

Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 3]).

Administration

Menopur: SubQ: Administer to alternating sites of the lower abdomen.

Repronex: SubQ: Administer to alternating sites of the lower abdomen. May also be administered IM

Hazardous agent; use appropriate precautions for handling and disposal (NIOSH, 2012).

Storage

Lyophilized powder may be refrigerated or stored at room temperature (3°C to 25°C [37°F to 77°F]). Protect from light.

Drug Interactions

There are no known significant interactions.

Adverse Reactions

Adverse effects may vary according to specific product, route, and/or dosage.

>10%:

Central nervous system: Headache (up to 34%)

Gastrointestinal: Abdominal pain (up to 18%), nausea (up to 12%)

Genitourinary: OHSS (up to 13%, dose related)

Local: Injection site reaction (4% to 12%)

1% to 10%:

Cardiovascular: Flushing

Central nervous system: Dizziness, malaise, migraine

Endocrine & metabolic: Breast tenderness, hot flashes, menstrual irregularities

Gastrointestinal: Abdominal cramping, abdominal fullness, constipation, diarrhea, enlarged abdomen, vomiting

Genitourinary: Ectopic pregnancy, ovarian disease, vaginal hemorrhage

Local: Injection site edema/pain

Neuromuscular & skeletal: Back pain

Respiratory: Cough increased, respiratory disorder

Miscellaneous: Infection, flu-like syndrome

Frequency not defined:

Cardiovascular: Stroke, tachycardia, thrombosis (venous or arterial)

Dermatologic: Angioedema, rash, urticaria

Genitourinary: Adnexal torsion, hemoperitoneum, ovarian enlargement

Neuromuscular & skeletal: Limb necrosis

Respiratory: Acute respiratory distress syndrome, atelectasis, dyspnea, embolism, laryngeal edema, pulmonary infarction, tachypnea

Miscellaneous: Allergic reactions, anaphylaxis

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity: Hypersensitivity and anaphylactic reactions have been reported; discontinue use for serious reactions and treat appropriately.

• Ovarian enlargement: May be accompanied by abdominal distention and/or abdominal pain and generally regresses without treatment within 2-3 weeks. If ovaries are abnormally enlarged on the last day of treatment, withhold hCG to reduce the risk of ovarian hyperstimulation syndrome (OHSS). Intercourse should be avoided with significant ovarian enlargement.

• Ovarian hyperstimulation syndrome (OHSS): OHSS, an exaggerated response to ovulation induction therapy, is characterized by an increase in vascular permeability which causes a fluid shift from intravascular space to third space compartments (eg, peritoneal cavity, thoracic cavity) (ASRM, 2008; SOGC-CFAS, 2011). This syndrome may begin within 24 hours of treatment, but may become most severe 7 to 10 days after therapy (SOGC-CFAS, 2011). OHSS is typically self-limiting with spontaneous resolution, although it may be more severe and protracted if pregnancy occurs (ASRM, 2008). Symptoms of mild/moderate OHSS may include abdominal distention/discomfort, diarrhea, nausea, and/or vomiting. Severe OHSS symptoms may include abdominal pain that is severe, acute respiratory distress syndrome, anuria/oliguria, ascites, dyspnea, hypotension, nausea/vomiting (intractable), pericardial effusions, tachycardia, or thromboembolism. Decreased creatinine clearance, hemoconcentration, hypoproteinemia, elevated liver enzymes, elevated WBC, and electrolyte imbalances may also be present (ASRM, 2008; Fiedler, 2012; SOGC-CFAS, 2011). If severe OHSS occurs, stop treatment and consider hospitalizing the patient (ASRM, 2008; SOGC-CFAS, 2011). Treatment is primarily symptomatic and includes fluid and electrolyte management, analgesics, and prevention of thromboembolic complications (ASRM, 2008; SOGC-CFAS, 2011). The ascitic, pleural, and pericardial fluids may be removed if needed to relieve symptoms (eg, pulmonary distress or cardiac tamponade) (ASRM, 2008; SOGC-CFAS, 2011). Women with OHSS should avoid pelvic examination and/or intercourse (ASRM, 2008; SOGC-CFAS, 2011).

• Ovarian neoplasms: Benign and malignant neoplasms have been reported (infrequently) in women receiving multiple-drug therapy for controlled ovarian stimulation; causal effect has not been established.

• Ovarian torsion: Has been reported following gonadotropin treatment; may be related to OHSS, prior ovarian torsion, prior or current ovarian cyst, polycystic ovaries, pregnancy, or prior abdominal surgery. Early diagnosis and prompt detorsion may limit the extent of ovarian damage.

• Pulmonary effects: Serious pulmonary conditions (atelectasis, acute respiratory distress syndrome, and exacerbation of asthma) have been reported.

• Thromboembolism: In association with and separate from ovarian hyperstimulation syndrome (OHSS), thromboembolic events have been reported. Use caution in women with personal or family risk factors for thrombosis.

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with hepatic impairment; safety and efficacy have not been established.

• Renal impairment: Use with caution in patients with renal impairment; safety and efficacy have not been established.

Special handling:

• Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 3]).

Other warnings/precautions:

• Appropriate use: To minimize risks, use only at the lowest effective dose. Monitor ovarian response with serum estradiol and vaginal ultrasound on a regular basis.

• Experienced physician: These medications should only be used by physicians who are thoroughly familiar with infertility problems and their management.

• Multiple births: May result from the use of these medications; advise patients of the potential risk of multi-fetal gestation and multiple births before starting the treatment.

Monitoring Parameters

Monitor sufficient follicular growth and maturation. This may be directly estimated by transvaginal sonographic visualization of the ovaries and endometrial lining. The combination of both ultrasonography and measurement of estradiol levels is useful for monitoring for the growth and development of follicles and timing hCG administration.

The clinical evaluation of estrogenic activity (changes in vaginal cytology and changes in appearance and volume of cervical mucus) provides an indirect estimate of the estrogenic effect upon the target organs and, therefore, it should only be used adjunctively with more direct estimates of follicular development (ultrasonography and serum estradiol determinations).

The clinical confirmation of ovulation is obtained by direct and indirect indices of progesterone production, as well as sonographic evidence of ovulation. The direct or indirect indices of progesterone production most generally used are: Rise in serum or urine LH, rise in basal body temperature, increase in serum progesterone, and menstruation following the shift in basal body temperature. Sonographic evidence of ovulation includes collapsed follicle, fluid in the cul-de-sac, features consistent with corpus luteum formation, and secretory endometrium.

Monitor for signs and symptoms of ovarian hyperstimulation syndrome (OHSS) for at least 2 weeks following hCG administration.

OHSS: Monitoring of hospitalized patients should include abdominal circumference, albumin, cardiorespiratory status, electrolytes, fluid balance, hematocrit, hemoglobin, serum creatinine, urine output, urine specific gravity, vital signs, weight (daily or as necessary) and liver enzymes (weekly) (ASRM, 2008; SOGC-CFAS, 2011).

Pregnancy Risk Factor

X

Pregnancy Considerations

Ectopic pregnancy, congenital abnormalities, spontaneous abortion, and multi-fetal gestations/births have been reported. The incidence of congenital abnormality may be slightly higher after ART than with spontaneous conception; higher incidence may be related to parenteral characteristics (maternal age, genetics, sperm characteristics). Menotropins are used for the induction of ovulation and with ART; use is contraindicated in women who are already pregnant.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience injection site irritation, nausea, vomiting, abdominal pain, headache, abdominal cramps, or bloating. Have patient report immediately to prescriber breast pain, enlarged breasts, tachycardia, jaundice, fast breathing, pale skin, skin discoloration, flu-like symptoms, signs of ovarian hyperstimulation syndrome (severe abdominal pain or bloating; severe nausea, vomiting, or diarrhea; excessive weight gain; shortness of breath; or change in how much urine is passed), or signs of blood clots (numbness or weakness on one side of the body; pain, redness, tenderness, warmth, or swelling in the arms or legs; change in color of an arm or leg; angina; shortness of breath; fast heartbeat; or coughing up blood) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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