Usage
Enclomiphene citrate is prescribed for the treatment of male hypogonadism (specifically, secondary hypogonadism) characterized by low testosterone levels and associated symptoms like reduced libido, erectile dysfunction, fatigue, and decreased muscle mass. In women, it’s used to treat infertility related to ovulatory dysfunction, particularly in those with polycystic ovary syndrome (PCOS). It is classified as a selective estrogen receptor modulator (SERM).
Enclomiphene’s mechanism of action involves competitive antagonism of estrogen receptors at the hypothalamic and pituitary levels. This reduces negative feedback inhibition, leading to increased secretion of gonadotropin-releasing hormone (GnRH). Consequently, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels rise, stimulating testosterone production in the testes (in men) and follicular development and ovulation in the ovaries (in women).
Alternate Names
Enclomiphene is the trans isomer of zuclomiphene, with zuclomiphene consisting of enclomiphene and clomiphene. It is also sometimes referred to as enclomifene citrate. Brand names include Androxal (though not yet FDA-approved as of February 16, 2025).
How It Works
Pharmacodynamics: Enclomiphene acts as an estrogen receptor antagonist, primarily in the hypothalamus and pituitary gland. By blocking estrogen’s negative feedback, it stimulates the release of GnRH, LH, and FSH, ultimately increasing testosterone production in men and promoting ovulation in women.
Pharmacokinetics: While detailed pharmacokinetic parameters aren’t fully established, existing data suggests oral administration leads to absorption with Cmax levels observed between 2 and 12 ng/ml. Steady-state levels appear to plateau with daily doses at around 25mg. Metabolism and elimination pathways are not fully elucidated as of today, February 16, 2025, though it is expected that it is mostly metabolized by the liver and excreted in the urine.
Mode of Action: Enclomiphene competitively binds to estrogen receptors in the hypothalamus and pituitary, effectively blocking estrogen’s inhibitory effect on GnRH release. The increased GnRH then stimulates the release of LH and FSH from the pituitary.
Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Enclomiphene primarily exhibits competitive antagonism at estrogen receptors. Currently, no significant interactions with other receptors, enzymes, or neurotransmitters have been documented.
Elimination Pathways: Precise elimination routes haven’t been definitively characterized as of February 16, 2025, however, it is thought to be primarily eliminated via hepatic (liver) metabolism followed by renal (kidney) excretion.
Dosage
Standard Dosage
Adults:
For men with secondary hypogonadism, the typical starting dose is 12.5 mg to 25 mg taken orally once daily. Some protocols suggest starting at 6.25 mg and titrating up as needed. Doses above 25 mg don’t appear to offer additional benefit in terms of LH stimulation. For women with infertility due to anovulation, the starting dose is often 50 mg daily for 5 days, beginning on the fifth day of the menstrual cycle. Subsequent cycles may utilize higher doses (up to 100 mg daily) if ovulation doesn’t occur.
Children:
Enclomiphene is not typically used in children, so there’s no established pediatric dosing.
Special Cases:
- Elderly Patients: Dosage adjustments may be necessary based on individual patient response and tolerance.
- Patients with Renal Impairment: Caution is advised, and dosage adjustments may be necessary.
- Patients with Hepatic Dysfunction: Dosage adjustments may be needed, as enclomiphene is likely metabolized by the liver.
- Patients with Comorbid Conditions: Care should be taken in patients with pre-existing conditions like liver disease, a history of blood clots, uncontrolled adrenal or thyroid dysfunction, or hormone-sensitive cancers.
Clinical Use Cases
Enclomiphene is not indicated for use in acute clinical scenarios like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations like status epilepticus or cardiac arrest. Its primary role is in chronic hormonal management.
Dosage Adjustments
Dosage adjustments should be made based on individual patient response, tolerance, and blood testosterone levels. Regular monitoring of hormone levels is essential for optimized therapy. Genetic polymorphisms affecting drug metabolism may also require dosage adjustments.
Side Effects
Common Side Effects
- Headache
- Nausea
- Diarrhea
- Hot flashes
- Dizziness
- Joint pain (arthralgia)
- Upper respiratory tract infection (e.g., common cold)
- Increased libido
- Acne
Rare but Serious Side Effects
- Ovarian hyperstimulation syndrome (in women)
- Visual disturbances (blurry vision, flashes of light)
- Pancreatitis (inflammation of the pancreas)
- Blood clots (thromboembolic events)
Long-Term Effects
- Potential increased risk of ovarian cancer (in women with prolonged use beyond recommended cycles)
Adverse Drug Reactions (ADR)
Severe allergic reactions, significant vision changes, signs of pancreatitis, or thromboembolic events require immediate medical attention.
Contraindications
- Pregnancy
- Breastfeeding
- Unexplained uterine bleeding
- Ovarian cysts or growths unrelated to PCOS
- Liver disease
- Uncontrolled adrenal or thyroid dysfunction
- Known allergy to enclomiphene or clomiphene
- Hormone-dependent cancers (e.g., breast, uterine, ovarian)
Drug Interactions
- Estrogens
- Oral contraceptives
- Lipid-lowering agents (statins)
- Thyroid hormone replacement
- Immunosuppressants
- Chemotherapy drugs (e.g., vinorelbine)
- Ospemifene
- Oxamniquine
- Oxprenolol
Alcohol should be avoided during enclomiphene therapy.
Pregnancy and Breastfeeding
Enclomiphene is contraindicated in pregnancy and breastfeeding due to potential risks to the fetus or infant. It may also reduce lactation.
Drug Profile Summary
- Mechanism of Action: SERM; estrogen receptor antagonist in the hypothalamus and pituitary, increasing GnRH, LH, and FSH.
- Side Effects: Headache, nausea, hot flashes, dizziness, visual changes (rare), increased libido.
- Contraindications: Pregnancy, breastfeeding, liver disease, unexplained uterine bleeding, ovarian cysts (unrelated to PCOS), hormone-dependent cancers.
- Drug Interactions: Estrogens, oral contraceptives, certain cholesterol medications, thyroid medications.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Men: 12.5-25 mg daily. Women: 50-100 mg daily for 5 days per cycle.
- Monitoring Parameters: Testosterone levels (men), follicle development/ovulation (women), liver function tests.
Popular Combinations
No specific combinations are consistently highlighted.
Precautions
- Pre-screening for liver, kidney, and thyroid dysfunction.
- Assess for unexplained uterine bleeding, ovarian cysts.
- Evaluate for hormone-dependent cancers.
- Caution in patients with history of blood clots.
- Monitor vision changes.
FAQs
Q1: What is the recommended dosage for Enclomiphene?
A: For men with hypogonadism: 12.5-25mg daily. For women with infertility: 50-100mg daily for 5 days per cycle, starting on day 5 of the menstrual cycle.
Q2: How does Enclomiphene work?
A: Enclomiphene acts as a SERM, blocking estrogen receptors in the hypothalamus and pituitary, leading to increased GnRH, LH, and FSH. This stimulates testosterone production (in men) and ovulation (in women).
Q3: What are the common side effects of Enclomiphene?
A: Common side effects include headache, nausea, hot flashes, dizziness, and increased libido.
Q4: Is Enclomiphene safe to use during pregnancy?
A: No, Enclomiphene is contraindicated during pregnancy and breastfeeding.
Q5: What are the contraindications for Enclomiphene?
A: Contraindications include pregnancy, breastfeeding, liver disease, unexplained uterine bleeding, and ovarian cysts unrelated to PCOS.
Q6: Can Enclomiphene be used with other medications?
A: Some drug interactions exist. Consult the “Drug Interactions” section for details and inform your physician about all medications you are taking.
Q7: How long does it take for Enclomiphene to work?
A: For men, symptomatic improvement may be seen within 2-4 weeks. For women, ovulation is typically monitored during treatment cycles.
Q8: What should I do if I miss a dose of Enclomiphene?
A: Take the missed dose as soon as you remember, unless it is almost time for the next dose. Do not double the dose.
Q9: Are there any long-term risks associated with Enclomiphene use?
A: Limited long-term safety data is available as of February 16, 2025. In women, prolonged use (beyond the recommended number of cycles) may increase the risk of ovarian cancer.
