What is the dose of clomifene (clomiphene) for a male patient with infertility?

Clomiphene Dosing for Male Infertility

For male infertility, clomiphene citrate should be administered at 25 mg orally daily for 25 consecutive days followed by a 5-day rest period, with this cycle repeated for at least 3 months. 1, 2

Dosing Protocol

• Standard regimen: 25 mg daily for 25 days, then 5 days off, repeated cyclically for a minimum of 3 months 1, 2
• The 3-month duration is necessary because spermatogenesis requires approximately 74 days to complete, so adequate time must be allowed to assess treatment response 2
• If patients fail to respond to 25 mg daily, a higher dose of 50 mg daily may be considered, though this is less commonly used 3

Patient Selection Criteria

Clomiphene should only be prescribed for men with documented low serum testosterone and abnormal semen parameters—not as first-line therapy for idiopathic infertility with normal testosterone levels. 1, 2

• Appropriate candidates include infertile men with low testosterone (hypogonadotropic state) and impaired semen quality 2
• Men with total motile sperm count <10 million and documented low testosterone may be considered for clomiphene therapy 2
• This medication is not FDA-approved for use in men and represents off-label prescribing 4, 1

Critical Limitations and Caveats

The benefits of clomiphene are distinctly limited compared to assisted reproductive technology (ART), which offers higher pregnancy rates and shorter time to conception. 4, 1, 2

• Only one study among multiple trials demonstrated statistically significant improvement in pregnancy rates with clomiphene, though most studies showed increased sperm concentrations 5
• A 2023 meta-analysis found clomiphene increased sperm concentration by 8.38 × 10⁶/ml and motility by 8.14%, with a mean pregnancy rate of only 17% (range 0-40%) 6
• Female partner age is the most critical factor determining conception success, and delaying ART for empiric clomiphene trials may reduce overall pregnancy chances 2

Treatment Algorithm

• Baseline assessment: Document low testosterone and abnormal semen parameters before initiating therapy 2
• Monitor response: Repeat semen analysis after at least 2.5 months (74 days) to assess spermatogenic response 2
• If no improvement after 3 months or if time-sensitive fertility concerns exist (particularly with advancing female partner age), transition directly to IVF/ICSI rather than continuing clomiphene 1, 2
• For men with total motile sperm count >10 million after treatment, intrauterine insemination (IUI) with ovarian stimulation may be considered before proceeding to IVF 2

Contraindications and Precautions

• Avoid in liver disease, especially decompensated cirrhosis, due to potential hepatotoxicity 1
• Never use in hypogonadotropic hypogonadism (HH) where exogenous gonadotropins or pulsatile GnRH are preferred first-line therapies 1
• At standard doses, clomiphene is generally well-tolerated with no serious adverse effects identified in clinical studies 5, 6
• Long-term effects remain unknown as clomiphene is not FDA-approved for male use 3

Non-Obstructive Azoospermia

For men with non-obstructive azoospermia (NOA), clomiphene has extremely limited evidence and should not delay surgical sperm retrieval options like microsurgical testicular sperm extraction (micro-TESE). 4, 2

• Patients with NOA should be informed that data supporting pharmacologic manipulation with SERMs (including clomiphene) prior to surgical intervention is minimal 4, 2