What is the recommended dose of Clomid (clomiphene citrate) for testosterone replacement therapy in men?

Clomiphene Citrate Dosing for Male Testosterone Replacement Therapy

Clomiphene citrate is NOT FDA-approved for testosterone replacement therapy in men, and the FDA label specifically addresses only female ovulation induction. 1 However, off-label use in men with hypogonadism has been extensively studied, with the most effective dosing being 25 mg every other day, titrated to 50 mg every other day if needed to achieve target testosterone levels of 550 ± 50 ng/dL. 2

Initial Dosing Strategy

Start with 25 mg clomiphene citrate every other day (or 3 times per week). 2, 3 This lower dose has demonstrated significant efficacy:

• Mean testosterone levels increased from 309 ng/dL at baseline to 642 ng/dL after 3 months of treatment with 25 mg daily dosing 3
• In a large prospective study of 86 men, 70% achieved target testosterone levels on just 25 mg every other day 2
• The 25 mg dose produces consistent hormonal responses with minimal side effects 3

Dose Titration Protocol

If target testosterone levels (550 ± 50 ng/dL) are not achieved after 6-8 weeks, increase to 50 mg every other day. 2, 4

• Only 30% of patients required the higher 50 mg every other day dose in long-term follow-up 2
• Alternative high-dose regimen studied: 100 mg three times per week showed 66% positive response rate, though this is less commonly used 5
• Measure testosterone levels 6-8 weeks after initiation or dose change 4

Monitoring Requirements

Check total testosterone, LH, FSH, and estradiol at baseline and 6-8 weeks after starting or adjusting dose. 2, 4

• Target testosterone: 550 ± 50 ng/dL (mid-normal range) 2
• Once stable, monitor testosterone twice yearly 2
• Expected hormonal changes include significant increases in testosterone (mean 2.5-fold), LH (mean 3-fold), and FSH (mean 2-fold) 4

Clinical Efficacy and Duration

Long-term treatment (mean 19 months) demonstrates sustained efficacy and safety. 2

• 67% of patients report symptomatic improvement 4
• All patients showed improvement in quality of life scores on validated questionnaires 3
• Pregnancy rates of 26% reported in partners of treated men 5
• Treatment can be continued safely for up to 15 months based on available data 5

Critical Advantages Over Testosterone Replacement

Clomiphene preserves fertility and prevents testicular atrophy, making it the preferred option for younger men desiring fertility preservation. 2

• Stimulates endogenous testosterone production rather than suppressing it 3
• Maintains spermatogenesis, unlike exogenous testosterone which impairs it 2
• Avoids exogenous testosterone dependency 2
• Mean age of treated patients in largest study was 29 years, with 64% seeking treatment specifically for infertility 2

Safety Profile and Side Effects

Clomiphene demonstrates excellent safety with minimal adverse effects at therapeutic doses. 2, 3

• Most common side effect: transient nipple tenderness (rare) 4
• No serious adverse events recorded in prospective studies 2, 3
• Additional benefit: significant reduction in total cholesterol (197 to 186 mg/dL) 3

Important Caveats

This is off-label use; the FDA has only approved clomiphene for female ovulation induction at 50-100 mg daily for 5 days per cycle. 1 The dosing regimens for male hypogonadism differ substantially from FDA-approved female dosing and represent established off-label practice based on research evidence.

Do not use clomiphene as monotherapy for erectile dysfunction - it addresses testosterone deficiency but does not directly treat ED. 6 If ED is present, PDE5 inhibitors should be added. 6

Clomiphene works only in hypogonadotropic hypogonadism (low testosterone with low-normal or low LH/FSH). It will not be effective in primary testicular failure where gonadotropins are already elevated. 4