Alprostadil Cream Does Not Impair Male Fertility
Alprostadil cream is safe for use in men attempting to conceive and does not affect male fertility or sperm parameters. This topical formulation is designed for local action with minimal systemic absorption, making it distinct from systemic medications that require fertility precautions.
Key Evidence Supporting Safety in Fertility
Alprostadil cream has poor systemic absorption (only 3% of treated patients experience systemic adverse effects), which limits any potential impact on spermatogenesis or hormonal function 1.
No fertility warnings exist in clinical guidelines for alprostadil use in men attempting conception. The 2025 EAU guidelines on male infertility extensively discuss medications requiring discontinuation before conception (methotrexate, mycophenolate, cyclophosphamide) but make no mention of alprostadil requiring cessation 2.
The mechanism of action is localized: Alprostadil cream works by relaxing smooth muscle in the corpus cavernosum through local prostaglandin E1 activity, without affecting testicular function or the hypothalamic-pituitary-gonadal axis 3, 4.
Clinical Context for Fertility Planning
Men with erectile dysfunction attempting conception can use alprostadil cream without concern for impaired fertility outcomes. The 2025 EAU guidelines recommend various ED treatments (PDE5 inhibitors, intracavernosal injections, topical alprostadil) without fertility restrictions 2.
Contrast with medications requiring discontinuation: The EAU explicitly states that cyclophosphamide requires 3 months discontinuation, methotrexate 1-3 months, and mycophenolate 1.5 months before conception due to teratogenic and gonadotoxic effects 2. No such recommendations exist for alprostadil.
Adverse effects are predominantly local: The most common side effects involve application site burning/erythema (12.2%), meatal pain (4.4%), and partner vaginal burning (2.1%), with no reported impact on sperm quality 5.
Practical Recommendations
Continue alprostadil cream during attempts to conceive without interruption, as there is no evidence of harm to fertility or offspring 4, 1.
Focus fertility evaluation on underlying causes: Men with ED attempting conception should undergo standard fertility assessment including semen analysis and hormonal evaluation (morning testosterone, FSH) to identify treatable causes of infertility 2.
Address modifiable risk factors: Smoking cessation, weight loss, and physical activity improve both ED and fertility outcomes more significantly than medication adjustments 2.
Important Caveat
The female partner may experience vaginal burning or irritation (reported in 2.1% of partners), which could theoretically affect coital frequency but does not represent a direct fertility concern 5. This can be mitigated by allowing adequate time for absorption before intercourse or using barrier protection initially.