Are there any medications that can increase male fertility?

Medications for Male Fertility Enhancement

For men with idiopathic infertility and normal testosterone levels, the benefits of medications like clomiphene citrate or FSH are small and outweighed by the advantages of assisted reproductive technologies (ART) such as IVF, which offer higher pregnancy rates and faster conception timelines. 1

Evidence-Based Medication Options by Clinical Context

For Hypogonadotropic Hypogonadism (HH)

• Exogenous FSH combined with hCG or gonadotropins can effectively initiate and maintain spermatogenesis in men with HH 1
• This represents the only FDA-supported indication where hormonal therapy has demonstrated clear efficacy for male fertility 1

For Idiopathic Infertility (Normal Testosterone)

Selective Estrogen Receptor Modulators (SERMs):

• Clomiphene citrate increases sperm concentration by a mean of 8.38 × 10⁶/ml and total motility by 8.14%, but these improvements do not translate to clinically meaningful pregnancy rate advantages over ART 2
• The AUA/ASRM guidelines explicitly state that SERMs like clomiphene or tamoxifen are "not FDA-approved for use in men" and their "benefits are small" compared to medically-assisted reproduction 1
• Pregnancy rates with clomiphene average only 17% (range 0-40%) across studies 2

Exogenous FSH:

• FSH injections for men without HH (baseline FSH normal or slightly elevated) show "measurable but limited fertility benefits" 1
• Treatment requires 3+ months to affect spermatogenesis, and the "incremental increase in pregnancy rates is small" 1
• The cost-to-benefit ratio is "questionable" given the prolonged treatment duration and modest outcomes 1

For Non-Obstructive Azoospermia (NOA)

• SERMs, aromatase inhibitors (AIs), and hCG have been used off-label to optimize hormonal profiles before surgical sperm retrieval 1
• Case series suggest potential benefits, but studies are typically uncontrolled, making it unclear whether medical intervention or more careful semen examination accounts for apparent improvements 1

Supplements and Antioxidants

There are no clear, reliable data supporting the use of vitamins, antioxidants, or nutritional supplement formulations for improving male fertility outcomes. 1 While current data suggest these are "likely not harmful," they are of "questionable value" 1

Critical Medications That HARM Male Fertility

Testosterone and Anabolic Steroids

• Exogenous testosterone administration suppresses gonadotropin secretion through negative feedback, potentially causing azoospermia 1, 3
• The FDA label for testosterone explicitly warns that "spermatogenesis may be suppressed through feedback inhibition" and that "reduced fertility is observed in some men taking testosterone replacement therapy" 3
• The impact on fertility may be irreversible 3
• Men misusing anabolic steroids experience "testicular atrophy, subfertility, and infertility" 3

Cyclophosphamide

• Doses ≥4000 mg/m² likely result in permanent azoospermia 1
• Doses <4000 mg/m² carry lower but still significant infertility risk 1
• Fertility preservation counseling is mandatory before initiating treatment 1

Sulfasalazine

• May cause reversible negative impact on sperm quality but does not increase adverse pregnancy outcomes 1
• Consider semen analysis if conception is delayed 1

Medications Safe to Continue When Attempting Conception

The following medications have no clinically relevant impact on offspring outcome and can be continued in men trying to conceive 1:

• Azathioprine/mercaptopurine
• Colchicine
• Cyclosporine
• Hydroxychloroquine and chloroquine
• Leflunomide
• Methotrexate ≤25 mg/week
• Mycophenolate
• NSAIDs
• Prednisone and prednisolone
• Sildenafil
• Tacrolimus
• TNF inhibitor biologics and non-TNF biologics

Common Pitfalls to Avoid

1. Do not prescribe testosterone to men attempting conception—it suppresses spermatogenesis rather than enhancing it 1, 3

2. Do not delay referral to ART while pursuing empirical medical therapy—the time cost of 3-6 months of medication trials with modest benefits may be particularly detrimental for couples where female partner age is a factor 1

3. Recognize that high disease activity itself impairs male fertility—controlling underlying rheumatic or systemic diseases with compatible medications is the best fertility strategy 1

4. Do not discontinue safe medications unnecessarily—drugs like methotrexate, leflunomide, and mycophenolate that would be stopped in women can be safely continued in men, as they show no evidence of increased birth defect risk 1

Clinical Algorithm

Step 1: Identify the underlying cause through hormonal evaluation (testosterone, LH, FSH, prolactin) 1

Step 2: If hypogonadotropic hypogonadism is confirmed, initiate FSH + hCG therapy 1

Step 3: If idiopathic infertility with normal hormones, counsel the couple that ART (IVF/ICSI) offers superior pregnancy rates compared to empirical medical therapy 1

Step 4: If the couple declines ART or has financial constraints, clomiphene citrate may be considered as a temporizing measure, but set realistic expectations about modest benefits 1, 2

Step 5: For men on gonadotoxic medications (cyclophosphamide), prioritize sperm banking before treatment initiation 1