Androxal (enclomiphene citrate) represents a significant advancement in the treatment of male hypogonadism, specifically addressing secondary hypogonadism with a targeted, non-testosterone mechanism of action. Unlike traditional testosterone replacement therapies (TRT), which introduce exogenous hormones and can suppress natural production, Androxal works by stimulating the body’s own endocrine pathways to restore physiologic testosterone levels. This oral medication selectively blocks estrogen receptors in the hypothalamus, leading to an increase in gonadotropin-releasing hormone (GnRH) pulsatility, subsequent luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion from the pituitary, and ultimately, endogenous testosterone production from the Leydig cells of the testes. It is indicated for adult males with documented hypogonadism who desire to preserve or restore fertility and testicular function, offering a paradigm shift from suppressive androgen therapies.

Features

• Active pharmaceutical ingredient: Enclomiphene citrate, the trans-isomer of clomiphene
• Pharmacologic class: Selective estrogen receptor modulator (SERM)
• Administration: Oral tablet
• Available strengths: 12.5 mg and 25 mg
• Mechanism: Antagonizes estrogen receptors at the hypothalamus, increasing GnRH pulse amplitude and frequency
• Prescription status: Rx-only, requiring diagnosis of secondary hypogonadism
• Manufacturing: Produced under current Good Manufacturing Practices (cGMP)
• Stability: Shelf-stable at recommended storage conditions

Benefits

• Restores physiologic, endogenous testosterone production without introducing exogenous hormones
• Maintains or improves testicular volume and spermatogenesis, preserving fertility—a critical advantage over traditional TRT
• Avoids the supraphysiologic testosterone peaks and troughs associated with gels, patches, or injections
• Demonstrates a favorable safety and tolerability profile in clinical studies with long-term use
• Provides a convenient oral dosing regimen, enhancing patient compliance compared to injectable or transdermal options
• Does not typically require concomitant human chorionic gonadotropin (hCG) therapy for testicular preservation

Common use

Androxal is primarily prescribed for the treatment of secondary hypogonadism (hypogonadotropic hypogonadism) in adult men. This condition is characterized by low serum testosterone levels in the presence of low or inappropriately normal LH and FSH levels. Common etiologies include obesity, metabolic syndrome, opioid use, pituitary disorders, or idiopathic causes. Patients typically present with symptoms such as low libido, erectile dysfunction, fatigue, decreased muscle mass, depressed mood, and cognitive changes. Androxal is particularly suitable for men who wish to maintain fertility, as it stimulates the hypothalamic-pituitary-gonadal (HPG) axis rather than suppressing it. It is also used off-label in some cases for the treatment of infertility associated with hypogonadism and for post-cycle therapy (PCT) in men who have used anabolic steroids, though these uses are not FDA-approved.

Dosage and direction

The recommended starting dose of Androxal is 12.5 mg administered orally once daily, preferably at the same time each day, with or without food. Based on clinical response and serum testosterone levels measured after approximately 4 weeks, the dose may be titrated up to 25 mg once daily if the 12.5 mg dose does not achieve target testosterone levels (typically aiming for the mid-normal range for adult males, approximately 400-700 ng/dL). Treatment should be initiated under the supervision of a physician experienced in managing male hypogonadism. Regular monitoring of serum testosterone, LH, FSH, and estradiol levels is recommended, particularly at dose initiation and following any adjustment. The duration of treatment is individualized based on therapeutic response and treatment goals. Tablets should be swallowed whole with a glass of water; they should not be crushed or chewed.

Precautions

Prior to initiating Androxal, a comprehensive medical evaluation should be conducted to confirm the diagnosis of secondary hypogonadism and rule out primary hypogonadism (hypergonadotropic hypogonadism) or other contraindications. Androxal is not recommended for use in patients with a history of pituitary tumors or disorders. Use with caution in patients with a history of depression, as mood changes have been reported. Regular ophthalmologic examinations are advised during treatment, as SERMs have been associated with visual disturbances (e.g., blurring, photophobia) in rare instances. Androxal may cause dizziness; patients should be cautioned about operating machinery or driving until they know how the medication affects them. It should be used with caution in patients with hepatic impairment, as metabolism is primarily hepatic. Safety and efficacy in patients with severe renal impairment have not been established.

Contraindications

Androxal is contraindicated in patients with known hypersensitivity to enclomiphene citrate or any component of the formulation. It must not be used in men with primary testicular failure (primary hypogonadism), as the mechanism of action requires functional Leydig cells. It is contraindicated in patients with untreated pituitary or hypothalamic tumors. Use is also contraindicated in pediatric patients and women, as safety and efficacy have not been established in these populations. Androxal should not be used concurrently with other SERMs or aromatase inhibitors without specific medical supervision due to the potential for complex endocrine interactions.

Possible side effect

The most commonly reported adverse reactions in clinical trials were headache, nausea, and dizziness, occurring in a small percentage of patients. Other less frequent side effects may include:

• Visual disturbances (e.g., blurred vision, floaters)
• Hot flashes
• Fatigue
• Mood swings or irritability
• Gastrointestinal discomfort (e.g., abdominal pain, diarrhea)
• Acne or other skin reactions
• Increased sweating
• Myalgia (muscle pain)
• Insomnia

Most side effects are mild to moderate in severity and often diminish with continued therapy. Serious adverse events are rare but may include severe visual symptoms or signs of an allergic reaction (e.g., rash, urticaria, swelling). Patients should be instructed to report any persistent or severe side effects to their healthcare provider promptly.

Drug interaction

Androxal is primarily metabolized by CYP2D6 and, to a lesser extent, CYP3A4. Concomitant use with strong inhibitors of these enzymes (e.g., paroxetine, fluoxetine, ketoconazole, clarithromycin) may increase enclomiphene plasma concentrations and the risk of adverse effects. Inducers of these enzymes (e.g., rifampin, carbamazepine, St. John’s Wort) may decrease its efficacy. Androxal may interact with other medications that affect estrogen pathways, such as other SERMs (e.g., tamoxifen, raloxifene) or aromatase inhibitors (e.g., anastrozole, letrozole), potentially leading to unpredictable endocrine effects. It may also interact with drugs that affect pituitary function. Patients should provide their physician with a complete list of all medications, including over-the-counter drugs and herbal supplements, before starting treatment.

Missed dose

If a dose of Androxal is missed, it should be taken as soon as remembered on the same day. If it is not remembered until the next day, the missed dose should be skipped, and the regular dosing schedule resumed. Do not double the dose to make up for a missed one. Maintaining a consistent dosing time is recommended to stabilize hormone levels. Patients should be advised to set a daily reminder to minimize the chance of missing doses.

Overdose

There is limited clinical experience with Androxal overdose. Based on its pharmacologic profile, acute overdose may lead to an exaggeration of its known adverse effects, such as severe headache, significant visual disturbances, nausea, vomiting, or dizziness. There is no specific antidote for enclomiphene citrate overdose. Treatment should be supportive and symptomatic, including gastric lavage or activated charcoal if ingestion was recent. Patients should be monitored for endocrine effects, and medical attention should be sought immediately. Hemodialysis is unlikely to be effective due to the high protein binding of enclomiphene.

Storage

Androxal tablets should be stored at room temperature, between 20°C to 25°C (68°F to 77°F), with excursions permitted between 15°C to 30°C (59°F to 86°F). Keep the medication in its original container, tightly closed, and protected from light and moisture. Do not store in bathrooms or other areas prone to dampness. Keep out of reach of children and pets. Do not use Androxal beyond the expiration date printed on the packaging. Properly discard any unused or expired medication as per local guidelines, preferably through a medicine take-back program.

Disclaimer

This information is intended for educational and informational purposes only and does not constitute medical advice. It is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or medication. Never disregard professional medical advice or delay in seeking it because of something you have read here. The information provided is based on clinical data available at the time of writing and may not be exhaustive. Individual patient responses to Androxal may vary.

Reviews

“After struggling with the side effects of testosterone gels, switching to Androxal was a game-changer. My testosterone levels are now consistently in the normal range, and my semen analysis parameters have improved significantly. The convenience of a daily pill cannot be overstated.” – M.B., age 42

“As an endocrinologist, I find Androxal to be an invaluable tool for men with secondary hypogonadism who are concerned about fertility. It effectively raises testosterone while preserving—and often improving—spermatogenic function. It fills a crucial gap in our therapeutic arsenal.” – Dr. A.L., Endocrinologist

“I was initially skeptical about an oral medication for low T, but the lab results speak for themselves. My energy, libido, and mood have all improved without the need for injections. The only side effect I experienced was mild hot flashes in the first week, which resolved quickly.” – R.K., age 51

“The clinical trial data for enclomiphene is robust and convincing. It offers a physiologic approach to treating hypogonadism, which is particularly important for younger men or those wishing to start a family. It’s a well-tolerated and effective option.” – Dr. S.P., Clinical Researcher

“After my pituitary surgery, I developed hypogonadism. Androxal has successfully restored my testosterone to normal levels without suppressing my natural axis. It’s reassuring to know I’m not causing long-term shutdown.” – T.J., age 38