Drugs that cause infertility in males:Information for Aspiring Fathers

Dr.Muhammad imran(Rph) B.sc,Pharm.D,M.phil(pharmaceutics)
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According Zegers-Hochschild et al., 2009 : Infertility is defined as the inability to conceive a child after one year of regular, unprotected sexual intercourse with the same partner.

  • According to the WHO  approximately one in every six people of reproductive age worldwide experience infertility in their lifetime.
  • Infertility affects 8% to 12% of couples of   reproductive age, with male factors contributing to 50% of these cases.
  • A study by Agarwal et al. found that male infertility rates were highest in Africa and Central/Eastern Europe. In contrast, the rates in North America, Australia, and Central and Eastern Europe were 4.5–6%, 9%, and 8–12%, respectively.
  • A study by Agarwal et al. found that male factors accounted for 20% to 70% of infertility cases, with the percentage of infertile men ranging from 2.5% to 12%
                                               
                                                          
Drug induced male infertility


  1. Anabolic-Androgenic Steroids(AAS)

  • A systematic review published in 2021 found that AAS use was associated with a significant decrease in sperm concentration, progressive motility, and normal sperm morphology.
  • A study published in 2020 reported that up to 57% of men using AAS experienced hypogonadism (low testosterone levels), which can lead to impaired spermatogenesis.

2. Chemotherapeutic Agents

  • A systematic review published in 2022 reported that up to 60% of male cancer survivors experienced infertility after chemotherapy treatment.
  • A study published in 2021 found that men treated with alkylating agents like cyclophosphamide had a higher risk of azoospermia (complete absence of sperm) compared to those who did not receive these agents.

3.Antidepressants

  • Kahn et al. (2019) found that men taking SSRIs had significantly lower sperm concentration, motility, and normal morphology compared to non-users.

4. Immunosuppressants

  • Yassen et al. (2021) found that men taking cyclosporine and mycophenolate mofetil had a higher risk of oligozoospermia and abnormal sperm parameters compared to healthy controls.

5. Anti-Epileptic Drugs (AEDs)

  • Shukor et al. (2020) reported that men taking valproic acid had significantly lower sperm concentration and motility compared to those not taking AEDs. 

Drug ClassSpecific DrugsEffects on Male Fertility
Anabolic-Androgenic Steroids (AAS)Testosterone derivatives (e.g., nandrolone, stanozolol)Decreased sperm count, motility, and normal morphology; testicular atrophy; suppressed testosterone production
Chemotherapeutic AgentsAlkylating agents (e.g., cyclophosphamide, cisplatin)Testicular damage; impaired spermatogenesis; azoospermia (complete absence of sperm)
Antimetabolites (e.g., methotrexate)Reduced sperm quality and motility
Purine analogs (e.g., mercaptopurine)Impaired spermatogenesis
AntidepressantsSelective Serotonin Reuptake Inhibitors (SSRIs) (e.g., fluoxetine, sertraline)Decreased sperm count, motility, and normal morphology
ImmunosuppressantsCyclosporineOligozoospermia (low sperm count); abnormal sperm parameters
Mycophenolate mofetilOligozoospermia; abnormal sperm parameters
Anti-Epileptic Drugs (AEDs)Valproic acidReduced sperm count and motility
TopiramateAbnormal sperm parameters
Anti-Inflammatory DrugsSulfasalazineImpaired sperm motility; oligospermia

6. Psychoactive drugs

  • Psychoactive drugs negatively affect male reproductive functions, including sexual urge, androgen synthesis, spermatogenesis, and sperm quality. They induce testicular toxicity by promoting ROS-dependent testicular and sperm oxidative damage, inflammation, and apoptosis

Psychoactive DrugEffects on Male Fertility
CannabisDecreased sperm count, motility, and viability
OpioidsDecreased testosterone levels, impaired spermatogenesis, reduced sperm quality
CocaineDecreased sperm count, motility, increased sperm abnormalities
MethamphetamineDecreased sperm count, motility, viability; increased sperm DNA fragmentation
Alcohol (excessive)Decreased testosterone levels, impaired spermatogenesis, reduced sperm quality

7. Antibiotics

a. Nitrofurans (e.g., Nitrofurantoin)

  • Reduced sperm count and motility.
  •  Nitrofurantoin has been shown to negatively affect sperm parameters, likely due to its oxidative effects .

b. Tetracyclines (e.g., Doxycycline)

  • These drugs can bind to calcium and affect sperm motility.
  • Temporary reduction in sperm quality.

8.Antihypertensive drugs

These include:

Antihypertensive Drug ClassEffects on Male Fertility
Calcium Channel Blockers (CCBs)Decreased sperm motility, increased sperm abnormalities
Angiotensin-Converting Enzyme (ACE) InhibitorsDecreased sperm count and motility
Angiotensin II Receptor Blockers (ARBs)Decreased sperm count and motility
Beta-BlockersDecreased sperm motility, increased sperm abnormalities

9. Drugs used to treat benign prostatic hyperplasia (BPH)

These include:
Drug ClassSpecific DrugsEffects on Male Fertility
Alpha-BlockersTamsulosin, Alfuzosin, Doxazosin, TerazosinMay cause retrograde ejaculation, reduced semen volume, and decreased sperm count and motility
5-Alpha Reductase InhibitorsFinasteride, DutasterideMay cause decreased semen quality, reduced sperm count, motility, and morphology
Phosphodiesterase Type 5 (PDE5) InhibitorsTadalafil, Sildenafil
Generally considered safe for fertility, but may cause temporary impairment of semen parameters
AnticholinergicsOxybutynin, TolterodineLimited data, but may potentially affect semen quality and sperm parameters
Combination TherapyDutasteride + TamsulosinCombination therapy may have additive effects on semen quality and sperm parameters



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