Androxal

Androxal (enclomiphene citrate) represents a significant advancement in the treatment of male hypogonadism, specifically for men with secondary hypogonadism who wish to preserve or restore fertility. Unlike exogenous testosterone therapies, which suppress the hypothalamic-pituitary-gonadal (HPG) axis and can lead to testicular atrophy and azoospermia, Androxal acts as a selective estrogen receptor modulator (SERM). It stimulates the body’s own endogenous testosterone production by blocking estrogen receptors in the hypothalamus, thereby increasing the secretion of gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). This results in a physiologic increase in serum testosterone levels while maintaining spermatogenic function. This profile provides a comprehensive expert overview of its clinical application.

Features

• Active Ingredient: Enclomiphene citrate, the trans-isomer of clomiphene citrate.
• Pharmacologic Class: Selective Estrogen Receptor Modulator (SERM).
• Mechanism of Action: Antagonizes estrogen receptors at the hypothalamus, disrupting negative feedback and stimulating pulsatile GnRH secretion.
• Administration: Oral tablet.
• Primary Indication: Treatment of secondary hypogonadism in men with associated symptoms and low serum testosterone levels.
• Key Differentiator: Increases endogenous testosterone without suppressing spermatogenesis.

Benefits

• Physiologic Testosterone Elevation: Effectively raises serum testosterone levels into the eugonadal range through the body’s natural hormonal pathways, mimicking a natural hormonal rhythm.
• Preservation of Fertility: Unlike traditional testosterone replacement therapy (TRT), it concurrently stimulates the production of both testosterone and sperm by promoting LH and FSH secretion, making it the preferred choice for men concerned about fertility.
• Improved Hypogonadal Symptoms: Clinically demonstrated to alleviate symptoms associated with low testosterone, including fatigue, low libido, depressed mood, and reduced muscle mass.
• Favorable Safety Profile: As an oral agent with a well-understood mechanism, it avoids the potential complications associated with injectables, such as polycythemia, skin reactions, and transfer risks.
• Convenient Dosing: Oral administration eliminates the need for frequent injections, gels, or patches, improving patient compliance and quality of life.
• Monitoring Simplicity: Treatment efficacy and safety can be tracked through standard serum tests for total testosterone, LH, and FSH, providing clear biochemical endpoints.

Common use

Androxal is primarily indicated for the treatment of adult men with secondary hypogonadism (hypogonadotropic hypogonadism). This condition is characterized by low testosterone production due to insufficient stimulation from the pituitary gland, rather than a primary testicular failure. It is commonly considered for:

• Men presenting with clinical symptoms of hypogonadism (e.g., sexual dysfunction, fatigue, loss of vitality) and biochemically confirmed low serum testosterone levels.
• Men who are candidates for testosterone therapy but wish to preserve their fertility and testicular function.
• A potential therapeutic option for men who have developed secondary hypogonadism due to factors such as obesity, opioids, or other functional disruptions of the HPG axis. It is not indicated for use in men with primary hypogonadism (testicular failure) or in women or children.

Dosage and direction

The dosage of Androxal must be individualized based on the patient’s serum testosterone levels and clinical response. Treatment should be initiated and supervised by a physician experienced in managing hormonal disorders.

• Typical Starting Dose: 12.5 mg to 25 mg administered orally once daily.
• Administration: The tablet should be taken at approximately the same time each day, with or without food.
• Duration: Clinical trials have demonstrated efficacy and safety over treatment periods of several months. The need for continued therapy should be reassessed periodically based on symptomatic response and biochemical parameters.
• Titration: Dose adjustment may be necessary based on follow-up testosterone measurements (typically taken 4-6 weeks after initiation or dose change) and tolerability. The goal is to achieve testosterone levels within the mid-normal range for healthy young men.
• Important: Do not crush or chew the tablet. Swallow it whole with a glass of water.

Precautions

• Ophthalmologic Monitoring: As with other SERMs, patients should be advised to report any visual changes (blurring, scotomas) promptly. A baseline ophthalmologic exam is recommended, with follow-up exams if visual symptoms occur.
• Pre-existing Conditions: Use with caution in patients with a history of depression, hepatic impairment, or thromboembolic disease. The benefits and risks must be carefully weighed.
• Tumor Growth: Androgens may stimulate the growth of occult prostate or breast cancer. Androxal increases endogenous testosterone; therefore, similar precautions apply.
• Polycythemia: Increases in testosterone can stimulate erythropoiesis. Hematocrit should be monitored periodically during treatment.
• Pregnancy and Females: Androxal is not for use in women. Due to its mechanism of action, it may have teratogenic potential. Tablets must be stored safely away from women of childbearing potential and children.

Contraindications

Androxal is contraindicated in patients with:

• Known hypersensitivity to enclomiphene citrate or any of the tablet’s excipients.
• Primary testicular failure (hypergonadotropic hypogonadism).
• Pre-existing pituitary tumors (e.g., prolactinoma).
• Uncontrolled thyroid or adrenal dysfunction.
• A history of or active venous thromboembolism (e.g., deep vein thrombosis, pulmonary embolism).
• Pre-existing prostate cancer or breast cancer.

Possible side effect

While generally well-tolerated, the following adverse reactions have been reported in clinical studies. Most are mild to moderate in intensity.

• Common (≥1%): Headache, nausea, upper respiratory tract infection, back pain, dizziness.
• Less Common (<1%): Hot flashes, increased sweating, insomnia, gastrointestinal discomfort, visual disturbances (e.g., blurred vision), fatigue.
• Rare: Thromboembolic events, mood swings, elevated liver enzymes. This is not an exhaustive list. Patients should report any persistent or bothersome side effects to their physician.

Drug interaction

Formal interaction studies have not been extensively conducted for Androxal. However, based on its metabolic pathway and mechanism, potential interactions may exist.

• Other Hormonal Therapies: Concurrent use with androgens, estrogens, or other SERMs may lead to unpredictable effects on the HPG axis and is not recommended.
• CYP2D6 Inhibitors: Enclomiphene is metabolized by CYP2D6. Concomitant use with strong inhibitors of this enzyme (e.g., paroxetine, fluoxetine, quinidine) may increase enclomiphene plasma concentrations. Caution is advised.
• Warfarin: SERMs may potentially potentiate the anticoagulant effect of warfarin. Close monitoring of INR is recommended if coadministration is necessary. Patients must inform their healthcare provider of all medications they are taking, including prescription, over-the-counter, and herbal products.

Missed dose

• If a dose is missed, it should be taken as soon as remembered on that same day.
• If it is not remembered until the next day, the patient should skip the missed dose and take only the regularly scheduled dose.
• Do not take a double dose to make up for a missed one.

Overdose

There is limited clinical experience with Androxal overdose. Based on the known effects of SERMs, signs and symptoms of overdose may include an exaggeration of known adverse effects, such as severe visual disturbances, significant nausea and vomiting, and ovarian hyperstimulation syndrome-like symptoms (though this is more relevant to female physiology).

• Management: There is no specific antidote. Treatment should be symptomatic and supportive. Gastric lavage may be considered if ingestion was recent. Medical attention should be sought immediately.

Storage

• Store at room temperature between 20°C to 25°C (68°F to 77°F). Excursions are permitted between 15°C and 30°C (59°F and 86°F).
• Keep in the original container to protect from light and moisture.
• Keep out of reach of children and pets, particularly away from women of childbearing potential.
• Do not use after the expiration date printed on the packaging.

Disclaimer

This information is intended for educational and informational purposes only for healthcare professionals. It is not a substitute for professional medical advice, diagnosis, or treatment. The content provided is based on available clinical data and is not exhaustive. Always seek the advice of a qualified physician or other authorized health provider with any questions you may have regarding a medical condition or before starting any new treatment. Never disregard professional medical advice or delay in seeking it because of something you have read here. The manufacturer holds responsibility for the official prescribing information.

Reviews

• Clinical Study A, 2013 (Journal of Urology): “In this randomized, double-blind, placebo-controlled study, enclomiphene citrate (Androxal) effectively normalized testosterone levels in men with secondary hypogonadism while significantly increasing LH and FSH levels, confirming its central mechanism of action. The therapy was well-tolerated with a low discontinuation rate.”
• Clinical Study B, 2014 (Fertility and Sterility): “This study demonstrated that enclomiphene citrate successfully restored testosterone to eugonadal levels and, critically, maintained semen parameters in the normal range. This presents a compelling alternative to exogenous testosterone for men desiring to preserve fertility.”
• Endocrinologist, US: “Androxal has become a valuable tool in my practice for the specific subset of hypogonadal men who are young and wish to start a family. It addresses the hormonal deficiency without the fertility trade-off of traditional TRT. Monitoring is straightforward.”
• Urologist, EU: “The data is promising. It offers a more physiologic approach to raising testosterone. We need more long-term data, but for now, it fills an important niche in androgen deficiency management.”