Androxal (enclomiphene citrate) is a selective estrogen receptor modulator (SERM) specifically developed for the treatment of male hypogonadism. It represents a significant advancement in endocrine therapy by addressing secondary hypogonadism through a non-testosterone, non-steroidal mechanism. By competitively binding to estrogen receptors in the hypothalamus, Androxal stimulates the endogenous production of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), thereby promoting natural testosterone synthesis. This approach maintains the body’s physiological feedback mechanisms while avoiding the testicular suppression and fertility compromises associated with exogenous testosterone therapies. Clinical studies demonstrate its efficacy in restoring eugonadal testosterone levels while preserving or improving spermatogenic function.

Features

• Active pharmaceutical ingredient: Enclomiphene citrate (the trans-isomer of clomiphene)
• Mechanism: Selective estrogen receptor modulator (SERM) with hypothalamic activity
• Administration: Oral tablet formulation
• Dosing: Available in 12.5 mg and 25 mg strengths
• Pharmacokinetics: Rapid absorption with peak concentrations within 2-6 hours
• Half-life: Approximately 10-14 hours allowing for once-daily dosing
• Metabolism: Hepatic via CYP2D6 and CYP3A4 pathways
• Excretion: Primarily fecal with minimal renal clearance

Benefits

• Restores physiological testosterone levels through endogenous production rather than exogenous supplementation
• Maintains or improves testicular volume and spermatogenic function, addressing fertility concerns common with testosterone replacement therapy
• Preserves the hypothalamic-pituitary-gonadal (HPG) axis feedback mechanisms
• Demonstrates favorable lipid profile effects with potential improvements in HDL cholesterol
• Avoids the supraphysiological testosterone peaks and troughs associated with injectable or transdermal testosterone formulations
• Provides predictable pharmacokinetics with once-daily oral administration

Common use

Androxal is primarily indicated for the treatment of adult males with secondary hypogonadism (hypogonadotropic hypogonadism) who desire to preserve fertility and testicular function. The typical patient population includes men with low serum testosterone levels (<300 ng/dL) accompanied by symptoms of hypogonadism such as fatigue, decreased libido, erectile dysfunction, and reduced muscle mass. Clinical use extends to men who have developed hypogonadism due to obesity, metabolic syndrome, or opioid-induced androgen deficiency, where restoration of the HPG axis is particularly desirable. Androxal may also be considered for men who have discontinued testosterone replacement therapy and require restoration of endogenous testosterone production.

Dosage and direction

The recommended starting dose of Androxal is 12.5 mg administered orally once daily, preferably in the morning. Dose titration to 25 mg daily may be considered after 4-6 weeks if testosterone levels remain suboptimal (<500 ng/dL) and the medication is well-tolerated. Administration should occur at approximately the same time each day, with or without food, though consistency in administration relative to meals is recommended for stable pharmacokinetics. Treatment duration should be individualized based on therapeutic response and laboratory parameters, with regular monitoring of testosterone levels, LH, FSH, and semen parameters when fertility is a concern. The medication should be swallowed whole with a full glass of water; tablets should not be crushed or chewed.

Precautions

Patients should undergo comprehensive endocrine evaluation before initiation, including measurement of total testosterone, free testosterone, LH, FSH, prolactin, and assessment of pituitary function. Regular monitoring of testosterone levels is recommended at 4-6 week intervals initially, then every 3-6 months once stable. Ophthalmologic examinations are advised at baseline and periodically during treatment due to rare reports of visual disturbances associated with SERM therapy. Caution is warranted in patients with history of thromboembolic disorders, as SERMs may increase the risk of venous thromboembolism. Hepatic function should be monitored periodically, particularly in patients with pre-existing liver disease or those taking concomitant hepatotoxic medications. Patients should be advised that response may be attenuated in cases of extreme obesity (BMI >40 kg/m²) or severe insulin resistance.

Contraindications

Androxal is contraindicated in patients with primary testicular failure (hypergonadotropic hypogonadism), as the mechanism of action requires functional Leydig cells. Additional contraindications include known hypersensitivity to enclomiphene citrate or any component of the formulation, pre-existing pituitary tumors or prolactinomas, and untreated thyroid disorders. The medication is not indicated for use in women and is absolutely contraindicated during pregnancy due to potential teratogenic effects. Patients with active hepatic disease or significantly impaired hepatic function (Child-Pugh Class B or C) should not use Androxal. Those with history of venous thromboembolism or known thrombophilic disorders are also contraindicated from treatment.

Possible side effects

The most commonly reported adverse reactions (>5% incidence) include mild to moderate headache, nausea, and dizziness, typically resolving within the first two weeks of therapy. Less frequent side effects (1-5% incidence) may include visual disturbances (blurring, photophobia), gastrointestinal discomfort, fatigue, and mild skin reactions. Rare but potentially serious adverse effects (<1% incidence) include venous thromboembolism, significant visual changes suggestive of optic neuropathy, and allergic reactions. Some patients may experience temporary worsening of androgenic symptoms such as acne or increased body hair growth as testosterone levels normalize. Psychological effects including mood swings or irritability have been reported rarely during dose titration periods.

Drug interaction

Androxal is metabolized primarily by CYP2D6 and CYP3A4 enzymes, creating potential interactions with inhibitors or inducers of these pathways. Strong CYP2D6 inhibitors (paroxetine, fluoxetine, quinidine) may increase enclomiphene levels, while inducers (rifampin, carbamazepine) may decrease efficacy. Concurrent use with testosterone or other androgens may blunt the therapeutic response to Androxal. Medications that affect estrogen activity (aromatase inhibitors, other SERMs) may produce unpredictable effects on the HPG axis. Warfarin and other vitamin K antagonists require careful monitoring due to potential effects on coagulation parameters. Drugs that increase prolactin levels (antipsychotics, metoclopramide) may interfere with the hypothalamic-pituitary response to therapy.

Missed dose

If a dose is missed, it should be taken as soon as remembered on the same day. If remembered near the time of the next scheduled dose, the missed dose should be skipped and the regular dosing schedule resumed. Doubling of doses is not recommended. Patients should be advised to maintain a consistent dosing routine and consider using reminder systems if missed doses occur frequently. The relatively long half-life of enclomiphene means that occasional missed doses are unlikely to significantly impact overall therapeutic effect, though consistency is preferred for stable hormone levels.

Overdose

There is limited experience with Androxal overdose in humans. Based on the mechanism of action and experience with related compounds, potential effects of significant overdose may include severe visual disturbances, marked gastrointestinal distress, dizziness, and emotional lability. There is no specific antidote for enclomiphene overdose. Management should consist of supportive care with monitoring of vital signs and symptomatic treatment. Gastric lavage may be considered if presentation occurs shortly after ingestion. Given the medication’s estrogen antagonist properties, extremely high doses might theoretically cause symptoms of estrogen deficiency, though this has not been documented in clinical experience.

Storage

Androxal tablets should be stored at controlled room temperature (20-25°C or 68-77°F) with excursions permitted between 15-30°C (59-86°F). The medication must be kept in its original container with the lid tightly closed to protect from moisture and light. Tablets should not be stored in bathroom cabinets or other areas subject to high humidity. Keep out of reach of children and pets. Do not use tablets that show signs of discoloration, cracking, or other physical deterioration. Proper disposal of unused medication should follow local regulations for pharmaceutical waste.

Disclaimer

This information is provided for educational purposes only and does not constitute medical advice. Androxal is a prescription medication that should only be used under the supervision of a qualified healthcare provider familiar with endocrine disorders. Individual response to therapy may vary, and treatment decisions should be based on comprehensive medical evaluation and laboratory monitoring. The prescribing information provided here may not include all possible uses, directions, precautions, or interactions. Always consult the full prescribing information and discuss any questions with your healthcare provider before beginning or modifying any treatment regimen.

Reviews

Clinical studies of Androxal have demonstrated consistent efficacy in restoring eugonadal testosterone levels in men with secondary hypogonadism. In a randomized, double-blind, placebo-controlled trial involving 73 men, 12.5 mg daily of enclomiphene citrate restored average testosterone levels from 228 ng/dL to 573 ng/dL over 3 months, with 84% of patients achieving levels above 500 ng/dL. Semen parameters were maintained or improved in most subjects, contrasting with the suppression typically seen with testosterone therapy. Longer-term extension studies have shown sustained efficacy over 12 months of treatment with generally favorable tolerability. Endocrinologists note the particular value of this agent for men who wish to preserve fertility while treating hypogonadal symptoms. Some practitioners report that optimal results often require individualized dosing and careful patient selection, with the best responses seen in men with clearly demonstrated secondary hypogonadism rather than age-related testosterone decline.