Medications / Supplements and Their Potential Impact on Male Infertility
Introduction to Medications / Supplements and Their Potential Impact on Male Infertility
Sperm production is a complex process that lasts approximately ten weeks, during which time sperm precursor cells are transformed into fully mature sperm. At any time during this process, sperm production can be influenced by outside factors including medications or supplements that may be taken. In general, topical medications (such as creams or ointments) are going to have much less systemic absorption, and typically have little impact on male fertility potential. Also, it must be remembered that certain medications/supplements may have more or less of an impact on different people depending on individual factors such as genetics and other medical problems that they might have. For example, most men taking exogenous androgens (like testosterone injections) have profound decreases in sperm production, but a relatively small percentage (<10%) of men can maintain good sperm counts while taking these medications.
Prescription Medications and male infertility
The following categories of medications are known to potentially have a significant negative impact on male fertility:
1) Antibiotics
2) Anti-depressant/Anti-anxiety medications
3) Anti-fungal/Anti-parasitics
4) Anti-seizure medications
5) Anti-Psychotics
6) Cardiovascular medications
7) Chemotherapy agents
8) Erectile dysfunction medications
9) Gastrointestinal medications
10) Gout Medications
11) Hormonally active agents
12) Immunomodulators
13) Immunosuppressant agents
14) Narcotics/opiates
15) Prostate medications
16) Other Medications
This website does not contain a complete list of all medications that can potentially have a negative impact on sperm quality - studies are constantly being performed to identify additional medications that can affect fertility. However, we have tried to include as many as possible of the most common agents that are known to impact sperm numbers and quality. It must also be noted that certain medications are going to have more of an impact on sperm quality in some men as opposed to others.
It is important that you have a discussion with your health care provider before making any changes to your medications. This website aims to provide you with information for your own knowledge, and you can share it with your personal physician if you learn something that may be pertinent to your situation. Decisions about which medications are right for you depend heavily upon individual factors, and the potential risks or benefits to stopping or changing any of your medications need to be adequately weighed by a health care professional familiar with your medical history and circumstances.
Antibiotics and male infertility
There is not a large amount of data of the impact on male infertility associated with most antibiotics. Listed below is the data of what is known on some different antibiotics:
1) Nitrofurantoin- This is the exception in that there is pretty clear evidence that nitrofurantoin has the potential for direct gonadotoxic effects on the testicles. Human studies have shown decreases in sperm counts and motility, and this medication should be avoided if possible in men trying to conceive. [Semet M. Andrology 2017]
2) Aminoglycosides (Gentamycin, Neomycin, Streptomycin)- Human studies have shown disruption of sperm production and decreases in sperm counts and motility (with Streptomycin potentially having less of an impact). [Semet M. Andrology 2017]
3) Macrolides (erythromycin, azithromycin, spiramycin)- Animals studies have shown testicular disruption of sperm production, while some human studies have seen lower motility with their use. [Schlegal PN. FertSteril 1991]. In vitro studies have shown decreases in sperm motility and viability. [Hargreaves CA HumReprod 1998] However, a double-blind crossover-controlled trial in 1984 showed no significant impact on semen parameters in men taking erythromycin. [Baker HW. IntJAndrol 1984]
4) Tetracyclines (doxycycline, minocycline, tetracyclines)- In vitro studies have shown decreases in sperm motility and fertilization capacity in sperm exposed to tetracycline in the lab. [Semet M. Andrology 2017]. However, multiple studies have shown a neutral effect or improvements in semen parameters in men treated with doxycycline for genital duct infections. [Hamada A. Urology 2011][Vicari E. HumReprod 2011][Comhaire FH. IntJAndrol 1986][Yanushpolsky EH FertSteril 1995]. Similar improvements in semen parameters have been seen in men treated for genital tract infections with minocycline and tetracycline. [Malallah YA. JChemother 1992][Taylor-Robinson D. PediatrInfectDis 1986]
5) Sulfonamides (sulfamethoxazole)- Decreases in sperm counts, motility, and morphology have been seen with the use of these medications. [Schlegal PN. FertSteril 1991] In vitro studies have also shown decreases in sperm counts and viability with higher dosage exposures. [Hargreaves CA HumReprod 1998]
6) Beta-Lactams (penicillins, carbapenems, cephalosporins)- In vitro studies showed no impact on motility with some reduction in sperm viability, with amoxicillin reported to show the least toxicity. [Hargreaves CA. HumReprod 1998]. Some decreases in semen parameters have been seen in animal studies, but no human studies have found a negative impact. [Semet M. Andrology 2017]
7) Fluoroquinolones (ciprofloxacin, levofloxacin, ofloxacin)- studies in men with genital duct infections have shown either improvements in semen parameters [Vicari E. HumReprod 2000], no significant impact [Krisp A. Andrologia 2003], or reversible negative effect [Andreessen R. Andrologia 1993]
Summary on Antibiotics
Multiple classes of antibiotic medications have been shown to have the potential for reversible decreases in semen parameters. However, infections can be dangerous and cause oxidative stress on the body which can be detrimental for sperm as well. Infection in the genital ducts can be especially damaging to sperm and antibiotics are recommended to be used for testicular and epididymal infections (though nitrofurantoin should likely be avoided if possible). [Semet M Andrology 2017]. Some of the more commonly used antibiotics in male infertility include cephalosporins, doxycycline, and ciprofloxacin which are not felt to be damaging to sperm in most patients.
ANTI-DEPRESSANT AND ANTI-ANXIETY MEDICATIONS and male infertility
Anti-depressant and anti-anxiety medications play an important role in many people’s lives but can also have an impact on the fertility potential of men. It is known that men with anxiety and depression can experience problems with ejaculation as well as sexual function prior to any treatment. [Norr L. Andrology 2016] Depression has also been found to potentially negatively impact testosterone levels in some men as well. [Steiger A. JPsychiatRes 1991] Most classes of anti-depressants/anti-anxiety medications are known to be associated with an increased risk of sexual side effects which can impact erections, libido, and ejaculation. [Beeder LA. IntJUrol 2019]. Though controversial, a number of studies have also shown these medications to have a negative impact on male fertility potential as well, though these effects appear to be reversible if the medication is stopped. We will now review the different classes of anti-depressant and anti-anxiety medications and their potential impact on male fertility.
Selective Serotonin Reupdate Inhibitors (SSRIs)
SSRIs are some of the most common medications used to treat problems like depression and anxiety, but many have been linked to potential problems with fertility potential in men. [Brezina PR. JReprodInfertil 2012] Examples of SSRIs include fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), citalopram (Celexa), and escitalopram (Lexapro). The negative impact of SSRIs is felt to be potentially due to oxidative stress, changes in the hormonal environment, as well as impaired ductal transport of sperm. [Beeder LA. IntJUrol 2019]. Studies of sperm in the lab show have shown that all SSRIs have some degree of spermicidal activity, with the most seen with sperm contact by fluoxetine. [Kumar VS. BioorgMedChemLett 2006].
Regarding testing in humans, a 2011 study of 25 men starting escitalopram found a decrease in sperm density, dropping from 68 million sperm/cc to 26.4 million/cc after 3 months of treatment, with a corresponding change in motility from 58.2% to 23.4%. [Koyuncu H. IntJImporRes 2011]. A trial of 60 men randomized to either sertraline or cognitive therapy for premature ejaculation showed lower sperm densities and morphology (but not motility) in the men treated with sertraline. [Akasheh G. Urology 2014]. A 2010 study of 35 men started on paroxetine did not show and changes in sperm counts, motility, or morphology, but there were significant elevations of sperm DNA fragmentation. [Tanrikut C. FertSteril 2010]. In contrast, a study of 74 men on various SSRIs for 6 or more months showed a decrease in sperm density from 184.1 million/cc at baseline to 61.4 million/cc with a drop in motility as well from 66% to 49%. [Safarinejad MR. JUrol 2008]. There appeared to be no significant differences in impact on semen parameters between citalopram, escitalopram, fluoxetine, paroxetine, and sertraline in this study. Several of the above studies (besides the previously mentioned 2010 Tanrikut) showed elevations in sperm DNA fragmentation as well with the use of SSRIs. [Akasheh G. Urology 2014][Safarinejad MR. JUrol 2008] In contrast to all of the above data, a more recent study of over 9000 men showed no significant changes in semen parameters in men taking SSRIs. [Pham MN. Urol 2022] Duloxetine has been found to not have a negative impact on semen parameters in a double-blind study. [Pujani N. Andrologia 2021]
SSRIs have a known potential impact on ejaculatory function including ejaculatory latency. Several of these medications (paroxetine, fluoxetine, and sertraline) are used as off-label treatments for premature ejaculation. [Alhamam A. FertSteril 2023]
For more information on sperm DNA fragmentation, please see the “Advanced Sperm Testing” section of this website.
Selective Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)
This class of medications include desvenlaxifine, duloxetine, levomilnacipran, and venlafaxine and have a high incidence (58-70%) of sexual-related side effects (in comparison to 25-73% for SSRIs). [Beeder LA. IntJUrol 2019]. According to the 2019 review, only 1 study had been performed on the effect of these medications and male fertility, and this was a mouse study which showed no significant changes in semen parameters with the use of venlaxafine. [Bandegi L IntJReprodBiomed 2018]
Norepinephrine-Dopamine Reuptake Inhibitors (NDRIs)
These medications include bupropion, dexmethylphenidate, diphenylprolinol, ethylphenidate, methylenedioxypyrovalerone, methylphenidate, pipradrol, prolintane, and sibutramine. A single case study found significant improvements in semen parameters in a man (previously on an SSRI) when he stopped bupropion (sperm counts improved from 21 million/cc to 41 million/cc and motility rose from 10% to 75%). [Tanrikut C. FertSteril 2010]. No further human studies have confirmed these findings, but in rats, higher doses of bupropion cause a decrease in sperm motility (with no changes seen at lower medication dosage). [Cavariani MM. JApplToxicol 2015]. Animal studies on methyphenidate and sibutramine show potential negative impacts on aspects of fertility but no human studies are currently available. [Beeder LA. IntJUrol 2019].
Tricyclic Antidepressants (TCAs)
Medications in this class include amitriptyline, nortriptyline, amoxapine, desipramine, doxepin, imipramine, protriptyline, and trimipramine. Despite relatively low rates of sexual dysfunction (around 30%), these medications are no longer commonly used due to significantly higher rates of other adverse side effects. [Beeder LA. IntJUrol 2019]. Studies in rodents have found negative effects on semen parameters as well as increases in chromosomal abnormalities. [Beeder LA. IntJUrol 2019]. Several human studies have shown decreases in sperm motility and morphology with the use of TCAs. [Alhamam A. FertSteril 2023]. Tricyclics have been associated with elevated prolactin levels in some men. In terms of ejaculatory function, imipramine has been used to treat retrograde ejaculation.
Monoamine Oxidase Inhibitors (MOAs)
Medications in this class are commonly used only in patients who have not responded effectively to other antidepressants, and include selegiline, isocarboxazid, phenelzine, and tranylcypromine. Rates of sexual dysfunction with MOAs is around 40% but data on fertility impact is minimal. As per a 2019 review of the topic, only 2 rat studies (on Selegiline) have been performed, and both actually showed improvements in semen parameters. [Beeder LA. IntJUrol 2019].
Atypical Antidepressants
These medications include mirtazapine, trazodone, nefazodone, tianeptine, agomelatine, vilazadone, and vortioxetine. Once again, there is limited data on the impact of these medications on male fertility. [Beeder LA. IntJUrol 2019]. Trazadone in rats was found to decrease semen parameters as well as increased levels of sperm DNA fragmentation. [Ilgin S. OxidMetCellLongev 2018]. In contrast, a rat study of mirtazapine and single human case study of agomelatine did not suggest a negative impact on male fertility parameters. [Beeder LA. IntJUrol 2019].
Summary for Antidepressant Medications
The use of antidepressant medications clearly has the risk of sexual side effects on libido, erections and ejaculation. A negative impact on semen parameters and DNA fragmentation have been demonstrated by multiple studies on men taking SSRIs, although these findings were not found in all studies. [Alhamam A. FertSteril 2023] [Pham MN. Urol 2022] Some clinicians have recommended that men taking SSRIs and TCAs considering stopping the medication or changing to a different class when they want to conceive, but there is not good data to counsel patients on the chances that such a change will significantly improve semen parameters. [Semet M. Andrology 2017] In addition, changing a patient’s antidepressant medications can be difficult (with extended and uncomfortable withdraw symptoms associated with some medications) and has the potential for increased risk of harm to the patient. If such medication changes are made, they should always be done under the close supervision of the patient’s medical provider who is managing their antidepressants (e.g. primary care provider or psychiatrist). Changing from an SSRI or TCA to another class of medications can be tricky, and the extremely sparse human data on the various classes of antidepressants make it extremely difficult to recommend particular alternatives. What is clearly needed is more research in the impacts of these medications on semen parameters and male fertility potential.
Antifungals and Antiparasitics and male infertility
Some antifungal and antiparasitic medications are known to have a potentially negative impact on sperm quality. The most common use of anti-fungal medications is with topical formulations, and these should not have a significant impact on a man’s semen parameters. However, several systemic medications can potentially impact male fertility- these include:
1) Ketoconazole- This is an antifungal medication that has the ability to impact hormonal levels, causing decreases in intra-testicular testosterone levels. Increased rates of ED and decreased sperm motility have been reported. [Hui EX. Andrology 2022] It is recommended to stop the use of ketoconazole in men trying to conceive. [Semet M. Andrology 2017]
2) Hydroxychloroquine- An antimalarial medication, it has been found to cause decreases in motility in animal studies and when tested on sperm in the lab. No definite recommendations have been made on the use of chloroquine in men trying to conceive due to a lack of data including human studies. [Semet M. Andrology 2017]
3) Niridazole- An antiparasitic medication, used to treat schistosomiasis which is called by flatworms. There is evidence that it can cause reversible abnormalities in semen parameters. [El-beheiry AH. ArchAndrol 1982]
Anti-seizure Medications and male infertility
Untreated epilepsy has been shown to be associated with decreased semen parameters. Unfortunately, the antiseizure medications that are used to treat epilepsy also appear to have the potential to cause further problems with semen parameters. [Webber MP. Epilepsia 1986]. Lower sperm density, motility, and morphology have all been reported with medications such as carbamazepine, phenytoin, oxcarbazepine, and valproate. [Brezina PR. JReprodInfert 2012]. From a practical standpoint, these medications often cannot be safely stopped due to the health and safety risks involved with recurrent uncontrolled seizures. [Semet M. Andrology 2017] Aside from one study which showed improved semen parameters in men who changed from sodium valproate to phenytoin, there is not much data on “better” antiseizure medications to possibly switch to which could potentially decrease the impact on semen parameters. [Hayashi T. IntJUrol 2005] However, there is some evidence that the negative impact of male fertility may be related at least in part to imbalances in the normal testicular-pituitary axis function, so treatment with hormonal medications (such as SERMs or HCG) may be able to mitigate some of the negative impact on fertility while men are taking anti-seizure medications. [Herzog AG. ArchNeurol 1986]
Anti-Psychotic Medications and male infertility
Antipsychotic medications can potentially impact male fertility indirectly. [Semet M. Andrology 2017] The “typical” anti-psychotics (phenothiazines: Haloperidol, Amisulpide) are known to have the ability to increase prolactin levels, which can lead to decreased levels of FSH, LH, and testosterone. This can potentially lead to abnormalities in sperm production and quality. These medications and their hormonal effects can also lead to decreased libido as well as erectile and ejaculatory problems (though the medication effects in these areas are sometimes difficult to distinguish from the impact of the underlying medical conditions themselves). [Semet M. Andrology 2017].
In contrast, the “atypical” anti-psychotics (e.g. Quetiapine, Ariprazole, Olanzapine, Clozapine) do not generally increase prolactin levels and therefore have less of a negative impact on hormone levels. Switching medication classes can be quite difficult but may offer a benefit to some men with fertility problems who are currently taking a “typical” class anti-psychotic medication. [Semet M. Andrology 2017]
Cardiovascular Medications and male infertility
There are many types of medications that are used to treat various cardiovascular problems. Some do not direct impact semen parameters but have the potential to affect fertility through an increased risk of erectile dysfunction, while other medications can potentially have a negative impact on sperm quality itself.
1) Spironolactone- This is a diuretic used to control hypertension. This medication has been shown to sometimes decrease testosterone levels and negatively impact sperm function. [Semet M. Andrology 2017]
2) Calcium channel blockers- Treatment of hypertension- examples: verapamil, nifedipine, diltiazem, amlodipine. Although the data in humans in sparse, there is quite a bit of laboratory data showing a negative effect of calcium channel blockers on sperm function. In the lab, when sperm are subjected to calcium channel blockers, there has been observed a decrease in both sperm motility and viability as well as changes in the structure of the head and tail regions. [Brezina PR. JReprodInfert 2012]. Lab studies have shown that sperm exposed to calcium channel blockers were unable to bind with an egg, but these findings have not been reproduced in small human studies and were contradicted by a 1997 study which showed normal fertilization rates in men taking these medications who were undergoing standard IVF. [Katsoff D. HumReprod 1997]. Changes in sperm concentration have been reported in retrospective studies but these have not been confirmed in randomized controlled trials [Guo D. WorldJMensHealth 2017] and the use of verapamil has been linked to hyperprolactinemia. [Romeo JH. ClinEndocrinol 1996]. Calcium channel blockers have also been suggested to potentially have an impact on ejaculatory abnormalities because of their effect on smooth muscle function. [Semet M. Andrology 2017]
3) Beta blockers- Treatment of hypertension, CHF and arrhythmias- examples: propranolol, metoprolol, carvedilol, atenolol, nebivolol. Animal studies have shown lower testosterone levels with use of beta blockers. There is limited data on the fertility effects of beta blockers in humans but a retrospective study in 2017 showed some negative impact on sperm volume, counts and motility but these have not been confirmed in randomized controlled trials [Guo D. WorldJMensHealth 2017]. One clear impact is that beta blockers can potentially have a negative effect on erectile function in some men. [Semet M. Andrology 2017]
4) ACE-inhibitors (ACE-Is)- Treatment of hypertension- examples: captopril, enalapril. Some animal studies and tests on sperm in the lab have shown a negative impact on sperm motility [Semet M. Andrology 2017] while others have actually shown an improvement in sperm counts and motility in rats taking this class of medication. [Okeahialam BN. ArchAndrol 2006]. In one retrospective human study, the use of ACE-Is was associated with lower ejaculate volumes and sperm motility [Guo D. WorldJMensHealth 2017]. However, two randomized trials actually showed improvements in sperm counts and motility on men taking ACE-I’s [Mbah AU ClinPharmacolTher 2012][Schill WB FertSteril 1994]
5) Methyldopa- A central-acting medication used to treat hypertension. Has the potential to increase prolactin levels, thereby leading to hypogonadism. [Semet M. Andrology 2017]
6) Digoxin (Lanoxin)- Cardiovascular medication used to treat heart problems like atrial fibrillation, atrial flutter, and heart failure. It has been associated with decreased testosterone levels in some men as well as lower libido and erectile dysfunction. No recommendations have been made on this medication in men trying to conceive. [Semet M. Andrology 2017]
7) Lipid-lowering medications- These include the statins (pravastatin, simvastatin, atorvastatin) and gemfibrozil. In rats, pravastatin has been associated with decreases in semen parameters. [Semet M. Andrology 2017]. However, human studies have not found any negative impact of the use of statins on male fertility potential. [Keihani S. Andrologia 2018]. Simvastatin and pravastatin also have the potential to impact androgen synthesis, while this is not seen with atorvastatin. [Semet M. Andrology 2017] A reduction in the fertility of rats has been found with the use of gemfibrozil but there is no data showing any negative impact in humans. [Semet M. Andrology 2017]
Summary of Cardiovascular Medications
Men trying to conceive with a new diagnosis of hypertension may want to start with an ACE-inhibitor if possible. [Semet M. Andrology 2017]. Beta blockers likely have minimal impact on sperm quality as well, but are associated with an increased risk of erectile dysfunction. Changing from spironolactone and/or calcium channel blockers to another class of anti-hypertensive medication may provide some fertility benefit but should always be done under the close supervision of the man’s medical provider who is managing their hypertension (i.e. primary care provider or cardiologist).
Chemotherapeutic Agents and male infertility
See “Cancer Treatment” in the "Medical Conditions and Male Fertility" section of this website for more information regarding the impact of chemotherapy on male fertility.
Erectile Dysfunction Medications and male infertility
Type 5 Phosphodiesterase inhibitors (PDE5i) are commonly used medications for erectile dysfunction, and include sildenafil (Viagra), vardenafil (Levitra) and tadalafil (Cialis). Multiple studies have shown that the medications in this class do not impact semen parameters [Purvis K. BrJClinPharmacol 2002][Aversa A. HumReprod 2000][Burger M. IntjImpotRes 2000], and other studies have even shown an improvement in counts and motility with these agents. [Dimitradis F. AsianJAndrol 2008][Rago R. JEndocrinInvest 2012]Dimitriadis F. BJUInt 2010] One study found a decreased motility in men taking tadalafil [Pomara G. FertSteil 2017] while another showed a potential impact on the sperm acrosomal reaction. [Fisch JD HumReprod 1998]. Shared decision making is recommended for use of these medications, but the majority of studies do not show a significant negative impact, and the positive impact on overall fertility with improved erectile function can be significant. [Alhamam A. FertSteril 2023]
PDE5i medications have been shown to cause prolonged latency of ejaculation in some men. [Ekmekcioglu O. Urology 2005] These medications are considered to be a potential treatment option for men with premature ejaculation. [Aversa A. IntJImpotRes 2011] However, due this effect, some men may experience delayed ejaculation and ejaculatory failure while using these medications. [Nacchia A. Urology 2024]
Alprostadil is a vasodilatory that either can be injected directly into the penis or absorbed through the urethra when placed as a small pill through the meatus (Muse). Alprostadil itself has not been found to negatively impact sperm motility and viability when tested in the lab. [Hellstrom WJG. JUrol 1998]. However, when medications are directly injected into the penis, some of the medication has been found to enter into the bloodstream. Alprostadil is often mixed with other medications whose impact on sperm have not been extensively studied, so penile injections should be used with caution in men trying to conceive. [Semet M. Andrology 2017]
Gastrointestinal Medications and male infertility
A number of drugs used to treat gastrointestinal problems may be problematic for men trying to conceive.
Medications for Inflammatory Bowel Disease (IBD). The following is a review of medications used to treat IBD. [Shin T. WorldJGastrointPharTher 2016] For more information on managing IBD, please see the “Medical Conditions and Male Infertility” section of this website.
1) Sulfasalazine- commonly used in the treatment of IBD, but also has uses in the management of rheumatoid and psoriatic arthritis. Numerous studies have shown that this medication is known to have a reversible negative impact on semen parameters in the majority of men who take it. [Mouyis M. SemArthRheum 2019] Studies have shown improved parameters and pregnancy in men wth IBD changing to mesalamine (5-ASA). The mechanism of action for the anti-fertility effect of sulfasalazine is currently not known. [Alhamam A. FertSteril 2023]. Most studies have not shown adverse pregnancy outcomes (in terms of the health of the baby) in men who conceive while taking sulfasalazine. [Mouyis M. SemArthRheum 2019]
2) Mesalamine (5-ASA)- this medication is generally felt to be much safer for male fertility than sulfasalazine. There have been case reports of decreased semen parameters in men started on mesalamine, but the general recommendations are to only stop this medication in men with very stable IBD. [Kjaergaard N Scand J Gastroent 1989]
3) Corticosteroids- used to treat relapses of IBD but not generally used for maintenance therapy. Short term use of corticosteroids generally not negative impact semen parameters or health, though prolonged use in high doses can lead to significant general health problems.
4) Thiopurines- include azathioprine and its active metabolite (6-MP)- used and an adjunct treatment for IBD. Although no significant changes are generally seen in sperm counts, one study did find lower sperm motility. [Grosen A. J Crohns Colitis 2019]. The literature also suggests a small potential increased risk of miscarriage and congenital abnormalities of offspring. It is therefore recommended to use contraception for men taking azathioprine and 6-MP. [Semet M. Andrology 2017].
5) Methotrexate- immunosuppressant medication used to treat autoimmune problems, and is a second line treatment for men with IBD not responding to thiopurines. [See “immunomodulator’ section below for more information]
6) Calcineurin inhibitors- these include cyclosporin A (CSA) and tacrolimus. Used for immunosuppression as calcineurin activated immune T cells. There is only limited data on the fertility impact of these medications in humans. [Alhaman A. FertSteril 2023]. In rats, the use of CSA has been associated with decreased testicular weight along with lower testosterone levels and semen parameters. To date, only small studies in humans have been performed, but these do not appear to show any significant decrease in male fertility potential. [Haberman JUrol 1991].
7) Antitumor necrosis factor (anti-TNF) medications: infliximib, natalizumab, vedolizumab, ustekinumab- these are biologic agents which are monoclonal antibodies against TNF-alpha, an immune system cytokine. Multiple studies have not found a negative impact on male fertility, semen parameters, or sperm DNA integrity. [Alhaman A. FertSteril 2023].
General recommendations for IBD medications: In men taking sulfasalazine, it is recommended to change to mesalamine at least 4 months prior to trying to conceive. In men taking mesalamine who have abnormal semen parameters, a trial of short periods off mesalamine could be tried if the man’s IBD symptoms are stable. There is insufficient evidence to support the stopping of methotrexate in men who need this medication to control their symptoms. [Shin T. WorldJGastrointPharTher 2016].
A few other GI-related medications for which there is some evidence that they may have a negative effect on sperm quality include:
1) Cimetidine (Tagamet)- H2 blocker for the treatment of gastroesophageal reflux (GERD), heartburn, and stomach ulcers. This medication has been found to have anti-androgen properties, with the ability to cause reversible decreases in semen parameters. [Semet M. Andrology 2017]
-Potential other H2 blocker alternatives: ranitidine (Zantac), famotidine (Pepcid), nizatidine (Axid)
2) Pantaprazole (Protonix)- proton pump inhibitor- found in one human study to negatively impact sperm motility and capacitation.
Potential PPI inhibitor alternatives which were not found to have a negative impact on sperm quality included: omeprazole (Prilosec) and lansoprazole (Prevacid). [Escoffier J. Andrology 2020]
Gout Medications and male infertility
Medications which are used to treat gout have the potential to impact semen parameters. The most information is available on colchicine which has been shown to cause testicular dysfunction in rats and decreases in the semen parameters of some men taking the medication. [Haimov-Kochman R. HumReprod 1998]. Rare cases of azoospermia have also been linked to colchicine in humans. [Merlin HE. FertSteril 1972]. However, a larger study of 540 young patients taking colchicine for an average of approximately 20 years did not show decreases in fertility potential as well as no increase in the health problems of their offspring. [Yu TF. SemArthritisRheum 1982.
Allopurinol is another gout medication with much less data available on its impact on male fertility. There is some evidence that men taking allopurinol have normal semen parameters but possibly a potential for a decrease in the fertilizing capacity of their sperm. [Simsek M. ReprodToxicol 2018]
Potential alternatives for treating gout include probenecid, NSAIDs, corticosteroids, and dietary modification.
Hormonally Active Agents and male infertility
Medications that impact hormone levels can have a significant negative impact on sperm production and quality. Examples of these medications include:
1) Exogenous androgens. These are a very common source of male fertility problems and are covered in their own section "Exogenous Androgens/Anabolic Steroids" in this website.
2) Treatments for advanced prostate cancer. These include gonadotropin-releasing agonists such as cyproterone, leuprolide (Lupron) and goserelin (Zoladex), as well as gonatropin-releasing hormone antagonists such as degarelix (Firmagon) and abarelix (Plenaxis). These medications cause a nearly complete suppression of gonadotropin secretion with subsequent decreases in testosterone and FSH stimulation of the testicles. Antiandrogen medications such as bicalutamide (Casodex) can decrease testosterone production. The results are typically reversible decreases in sperm counts and motility with potential azoospermia. [Alhaman A. FertSteril 2023]
3) Estrogen therapy. This may decrease sperm function and potentially increase the risk of testicular cancer.
Immunomodulators and male infertility
Monoclonal antibodies- trastuzumab, alemtuzumab, rituximab, cetuximab, bevacizumab, omalizumab, anakinra. These medications can be used in the treatment of certain types of cancer as well as rheumatoid arthritis. There is little to no evidence of a negative impact on fertility potential in humans and animal studies have not shown significant concerns as per a review of the literature in 2017. [Semet M. Andrology 2017] Current recommendation on its use in men are not possible due to a lack of data.
TNF-alpha inhibitors- infliximab, adalimumab, etanercept, golimumab, certolizumab. These medications reduce inflammation and are used to treat problems such as rheumatoid arthritis, ulcerative colitis and Crohns disease. There is very little data available on these medications and their impact on fertility. Infliximib has been correlated with an increase in ejaculate volume and decrease in motility, but no impact on overall infertility has been reported. [Semet M. Andrology 2017]. Some studies have reported an increase in semen parameters with better control of a man’s inflammatory condition with the use of these TNF-alpha inhibitors. [Mouyis M. SemArthRheum 2019] These medications are currently not recommended to be discontinued in men trying to conceive.
Dabrafenib (Tafinlar) is a medication which is used to treat melanoma, and vismodegib (Erivedge) is used to treat basal cell carcinomas of the skin. These medications have shown testicular toxicity seen in animal studies. Recommend freezing sperm if possible before treatment and stopping this medicine prior to conceiving. When the female partner is pregnant it is recommended to use safe sex (e.g. condom use) due to teratogenic concerns. [Semet M. Andrology 2017]
Ipilimumab (Yervoy)- monoclonal antibody used to treat cancer. Decreased testicular volume has been seen in animals as well as decreases in pituitary function. Recommended to freeze sperm prior to starting treatment. [Semet M. Andrology 2017]
Leflunomide (Arava)- Treatment of rheumatoid arthritis. Testicular toxicity seen in animal studies but effect in humans unknown. Recommendation to use contraception in men taking this medication. [Semet M. Andrology 2017]
Thalidomide (Thalomid)- Used to treat skin problems and multiple myeloma. Testicular atrophy in animal studies and the drug is found in the semen of men taking it. Recommended to stop this medication in men trying to conceive due to teratogenic concerns. [Semet M. Andrology 2017]
Interferon alpha- Used to treat certain cancers as well as chronic viral infections. Changes in semen parameters in animal studies but no known problems seen in humans. Recommendation that patients taking this medication do not need to freeze sperm or stop medication when trying to conceive. [Semet M. Andrology 2017]
Immunoglobulins- used to treat primary immunodeficiency. No animal or human studies and therefore no recommendations possible. [Semet M. Andrology 2017] treat certain types of cancer.
Sorafenib (Nexavar)- tyrosine kinase inhibitor used to animal studies but reversible effect 10 weeks after finishing treatment. [Semet M. Andrology 2017]
Azathioprine (Imuran]- immunosuppressive medication used to treat medical conditions such as SLE. Most studies on male use of azathioprine have shown no detrimental impact on semen parameters or birth defects with only one case report showing decreased morphology. Multiple studies have shown trends toward improved semen parameters with better control of the underlying medical condition with the use of azathioprine. [Mouyis M. SemArthRheum 2019]
Leflunomide [Arava]- pyrimidine synthesis inhibitor. Used to treat immunologic problems like rheumatoid arthritis. Very little data is available but individual case reports have not found an association with fertility problems in men. [Mouyis M. SemArthRheum 2019]
Methotrexate- dihydrofolate reductase inhibitor that can be used both as a cytotoxic chemotherapeutic agent as well as to treat inflammatory arthritis. Reversible decreases in semen counts have been reported in some men taking methotrexate for psoriasis [Sussman Arch Derm 1980] and small studies have shown increases in sperm DNA fragmentation as well. [Ley D. Gastroenterol 2018]. Earlier recommendations were to stop the medication 3 to 4 months prior to starting to try to conceive. However, subsequent studies have not confirmed decreases in semen parameters or DNA fragmentation in men on methotrexate for rheumatology problems. [Grosen A. Inflamm Bowel Dis 2022][Perez-Garcia LF. AnnRheumDis 2023]. In summary, the majority of studies have shown no negative impact of methotrexate on semen parameters and that low-dose methotrexate used in the treatment of inflammatory disorders does not increase the risk of fetal malformations. [Mouyis M. SemArthRheum 2019]. A study of 223 children born to men taking methotrexate confirmed no increased risk of congenital anomalies, pre-term births, or being small for gestational age. [Zaren P. FertSteril 2023]
Baricitinib (Olumiant)- immunomodulatory agent used in the treatment of rheumatoid arthritis, alopecia areata, and Covid-19. Birth defects have been noted in animal studies so it has been recommended to stop this medication for 1 month prior to trying to conceive. [Hui EX. Andrology 2022]
Sulfasalazine- (see Gastrointestinal Medications” section above)
Immunosuppressant Agents and male infertility
1) Calcineurin inhibitors (CNIs)- these commonly used immunosuppressive medications include cyclosporin A (CSA) and tacrolimus. In rodent models, CSA has been found to have a negative impact on testicular function and semen parameters [Gawish AM. JBasApplZoo 2016], although human studies have not shown dramatic decreases in fertility potential of men taking these medications. [Semet M. Andrology 2017]. Animal studies on tacrolimus point to less of a negative impact on semen parameters, but data from human studies are limited. [Lundy SD. TranslAndrolUrol 2019]. The impact on hormone levels appears to be similar between men taking CSA and tacrolimus. [Kantarci G. TranplantProc 2004]. Recommendations are that CSA does not need to be discontinued in men who are trying to conceive, but no recommendations are currently available for tacrolimus due to a lack of data. [Semet M. Andrology 2017].
2) mTOR (rapamycin) inhibitors- these medications include sirolimus, everlimus, and temsirolimus and inhibit lymphocyte proliferation. These medications have been associated with reversible negative changes in semen sperm counts and motility along with decreased pregnancy rates. [Zuber J. AmJTransplant 2008]. Testicular atrophy and azoospermia have also been reported with the use of mTOR inhibitors. [Alhaman A. FertSteril 2023]. Potential teratogenic changes seen in sperm with animal models. It has been recommended to cryopreserve sperm in men to be started on medications like sirolimus and use contraception while men are taking this medication. [Semet M. Andrology 2017].
3) Mycophenalate [Cellcept]- antimetabolite immunosuppressant agent used in transplantation patients and inflammatory conditions like SLE. This medication has been shown to decrease semen parameters in animals, though this has not been studied in human studies. [Lundy SD. TranslAndrolUrol 2019] Human studies have not shown significant negative impacts on male fertility or adverse birth outcomes in children fathered by men taking mycophenalate. [Mouyis M. SemArthRheum 2019]
4) Corticosteroids- Studies have not shown significant long-term negative effects on sperm production in men taking shorter course of oral corticosteroids. [McDonald JH. JUrol 1956]. Long-term high dose corticosteroid use has the potential to impact the hypothalamic-pituitary-gonadal axis, and can lead to a number of other general health problems such as osteoporosis, thinning of the skin, weight gain, fluid retention, and an increased risk of infection and tumors. [Alhamam A. FertSteril 2023] In the treatment of immunologically-related fertility problems such as anti-sperm antibodies, low dose corticosteroids have been associated with improved semen parameters. [Omu AE. EurJObsGenReprodBiol 1996]
In summary, low dose corticosteroids are not generally recommended to be stopped for fertility reasons in men who are trying to conceive and the potential benefits of stopping long term higher dose corticosteroids must be weighed against the negative health impact of stopping treatment for that particular health problem which it is helping to manage. [Semet M. Andrology 2017]
PAIN MEDICATIONS and male infertility
NARCOTICS/OPIOIDS
The United States is in the midst of an opioid crisis with over 1.5 million people suffering from prescription opioid use problems. Commonly used opioids used in the U.S. include:
1) Codeine (Tylenol #3, Paramol, Nurofen Plus)
2) Hydrocodone (Vicodin, Norco, Lorcet, Lortab)
3) Oxycodone (OxyContin, Percocet, Roxicodone, Tylox)
4) Morphine (Duramorph, Avinza, Kadian)
5) Fentanyl (Durogesic, Actiq)
6) Methadone
Opioid receptors can be found in the male reproductive tract. Although short-term use of narcotics for acute pain does not appear to have any significant impact on male fertility potential, the long term use of these medications has been linked to decreases in sperm motility, morphology, and testosterone levels. [Safarinejad MR. ReprodToxicol 2013]. Suppression of the HPG axis occurs in 21-86% of men taking long term opioids with subsequent risk of hypogonadism and decreased sperm production. [Alhamam A. FertSteril 2023] Some narcotics seem to have more of a negative impact on the HPG axis than others. In men on chronic opioid treatment, buprenorphine appears to have less of a negative impact on gonadotropins than methadone. [Yee A. JSexMed 2018][Hallinan R. InJAndrol 2009]. There is also evidence of a direct negative impact on testicular function with long term opioid use as well which can lead to decreases in sperm abnormalities as well as elevations of levels of sperm DNA fragmentation. [Drobnis EZ. AdvExpMedBiol 2017]. Other specific opioids which have been associated with negative impacts on semen parameters include heroin, morphine, butorphanol, fentanyl, and tramadol. [Alhamam A. FertSteril 2023]
NON-OPIOD PAIN MANAGEMENT
Acetaminophen (Tylenol) is a commonly used over-the-counter (OTC) pain medication that is considered to be relatively safe (but can cause severe liver damage if taken in overdose quantities). Although there is no good data in humans, a study of rats taking acetaminophen daily for between 3 to 9 months showed decreases in semen parameters as well as increases in sperm DNA fragmentation. [Adebi N. MiddEastFertSocJ 2017].
Aspirin and non-steroidal anti-inflammatories (NSAIDs)
Studies on these medications suggest that long term (>6 months) use can lead to decreases in sperm counts and quality in some men. These were generally dose-related and reversible. [Semet M. Andrology 2017]. A study of 31 men in 2018 found that taking ibuprofen (Aleve/Motrin) at a dose of 600mg twice a day showed alterations in their testicular-pituitary axis function resulting in hypogonadism (low testosterone), though the direct impact on semen parameters was not evaluated. [Kristenen DM. PNAS 2018]
SUMMARY OF PAIN MEDICATION USE
There is ample evidence that long-term narcotic use is detrimental to sperm quality, though short-term use of these medications for an acute event (such as recovery after a surgical procedure) likely has no significant impact. The prolonged use of acetaminophen and ibuprofen may have some negative impact on fertility potential in men, though the data is extremely sparse. However, if these medications are needed for a man to avoid long-term narcotic use, these non-opioid alternatives appear to be a much better choice in terms of maintaining good sperm quality. The general recommendation for non-narcotic pain medications such as NSAIDs is that they generally do not need to be stopped in men trying to conceive, especially if semen parameters are normal. [Semet M. Andrology 2017].
Prostate Medications and male infertility
Benign enlargement of the prostate (BPH) can cause voiding symptoms (such as slow urinary flow and decreased bladder emptying) and has been associated with an increased risk of ejaculatory problems as well. [Avellino G. FertSteril 2017] However, many of the treatments for BPH can actually worsen male fertility potential further. There are 2 main classes of medications (as well as some non-prescription supplements) which are commonly used to treat BPH, and all have the potential to negatively impact male fertility.
1) Alpha-blockers
Alpha-blockers medication help to relax the smooth muscle in the prostatic urethra and bladder neck region, thereby opening up the channel to the flow of urine. Unfortunately, some alpha blockers cause ejaculatory problems, including retrograde ejaculation and even complete ejaculatory failure in some circumstances. Alpha blockers also have been shown to decrease the quality of semen parameters as well, including sperm counts and motility. [Hellstrom WJ. JAndrol 2009]. However, not all alpha blockers have the same impact on male fertility. Tamsulosin (Flomax) is a commonly used and effective oral medication for BPH. Unfortunately, many men taking tamsulosin experience a decreased ejaculatory volume with complete ejaculation failure seen in about 35% of men in some studies. [Kusman AM. FertSteril 2020]. Rates of reported reversible clinical ejaculatory problems with the use of tamsulosin generally range from 6%-18% depending on the dosages used. [Bearelly P. FertSteril 2021]. One study showed that changing to every other day dosing of tamsulosin resolved ejaculatory symptoms in 63% of patients without an appreciable worsening of urinary symptoms. [Goktas S. JUrol 2006]. Even higher rates of ejaculatory dysfunction have been seen with the use of silodosin (Rapaflo) in multiple studies. [Sakata K. BMCUrol 2012][Bearelly P. FertSteril 2021] In contrast, alfuzosin (Uroxatral) does not appear to have a negative impact on sperm transport in most men. [Andersson KE. BJUInt 2003] Older alpha blockers (terazosin and doxazosin) also seem to have very low rates of ejaculatory dysfunction associated with their use. [Bearelly P. FertSteril 2021]
2) 5-alpha reductase inhibitors (5ARIs)
These medications are used to shrink the size of enlarged prostates over time and include finasteride (Proscar), dutasteride (Avodart). Unfortunately, this class of medications can also decrease semen quality even in low doses. [Overstreet JW. JUrol 1999] A 2013 study of 14 men being seen for infertility showed a 11.6 fold increase in sperm counts (from 1.48 million sperm/cc to 23.54 million/cc) when finasteride was discontinued, with a smaller increase in sperm motility (from 16.8% to 25.9%). [Samplaski MK. FertSteril 2013]. Reversible decreases in total sperm count and motility were noted with the use of 5ARIs, with a return to baseline parameters 24 months after discontinuation. [Amory JK. JClinEndocrinolMet 2007]
3) Saw palmetto
Saw palmetto is an herbal supplement made from the berries of the Serenoa repens plant. It is a commonly used over-the-counter treatment for BPH and its mechanism of action is felt to be similar to that of 5-alpha reductase inhibitors. The impact of saw palmetto has not been extensively studied, but laboratory studies subjecting sperm to high levels of saw palmetto were noted to have a negative impact on sperm motility. [Ondrizek RR. Andrology 1998]
OTHER MEDICATIONS THAT CAN AFFECT SPERM PRODUCTION
A number of other drugs may cause fertility-related problems in men:
1) Hydroxyurea- an antimetabolite medication used in the treatment of sickle cell anemia (as well as leukomia and other malignancies). Sickle cell anemia can reduce male sperm production itself through ischemic end-organ damage of the pituitary gland and testicles. However, hydroxyurea can have a further significant impact on sperm production as well, with studies showing 86% of men decreasing total sperm counts at 6 months. Decreases in sperm counts can be severe leading even to complete azoospermia. [Bachir D. Blood 2012] Case studies have shown that impairments in sperm production can sometimes recovery upon cessation of treatment but often persist. [Grigg A. IntMed J 2007]. Newer alternative treatments for sickle cell anemia include crizanlizumab (Adakveo) which is a monoclonal antibody therapy. Another treatment option not felt to significantly impact male fertility is voxelotor (Oxbryta) which works by restoring RBCs to their normal shape.
2) Ribavirin (Moderiba)- This is an anti-viral medication which is used to treat chronic hepatitis C as well as severe viral lung infections from respiratory syncytial virus (RSV). Reversible decreases in semen parameters as well as increased DNA fragmentation have been found in human studies, with DNA changes lasting up to 8 months after stopping the medication. It is recommended to freeze sperm prior to starting therapy and stopping the medication 7 months prior to starting to try to conceive. The use of contraception is also recommended in patients taking this medication. [Semet M. Andrology 2017]
3) Anti-retroviral medications- These medications are used to treat HIV infections. Some studies have shown improvements in semen parameters treated for HIV. [Robbins WA. JInfectDis 2001][Akang EN. Andrologia 2022]. However, other studies have shown a negative impact on sperm motility and morphology with anti-retroviral treatments. [Kehl S. ArchGynecolObstet 2011][Bujan L. JAndrol 2007]. Despite the decrease in semen parameters shown in prospective studies, these medications are obviously not recommended to be discontinued as their impact is balanced by the positive role in controlling the chronic viral infection which itself often has a significant negative impact on male fertility potential. [Semet M. Andrology 2017]
4) Acyclovir (Zovirax)- used to treat herpes infections, chicken pox, and shingles. Animal studies have shown decreases in semen parameters, though no negative impact has been seen in humans. There are no current recommendations to stop the medication in men trying to conceive and any negative impact should resolve within 70 days of stopping the medication. [Semet M. Andrology 2017]
5) Danazol: A synthetic steroid with a structure similar to testosterone. Used to treat rare problems like idiopathic angioneurotic edema. Its androgenic effects are like exogenous androgens thereby causing decreases in FSH and LH secretion which can negatively impact sperm production. [Dmowski WP. FertSteril 1979]
6) Low dose oral finasteride (Propecia): used in the treatment of male pattern hair loss. Propecia is low dose finasteride (1mg). Multiple studies have shown conflicting results on potential negative impacts on sperm numbers and quality as well as DNA fragmentation. Shared-decision making is recommended for men with abnormal semen parameters taking these oral low dose finasteride. [Alhaman A. FertSteril 2023]. Potential alternatives for men with male pattern baldness is minoxidil (Rogaine) as well as topical finasteride.
7) Retinoic agents- isotretinoin, retinoic acid, acitretin- metabolites of vitamin A, these medications are used in the treatment of acne as well as certain types of leukemia. Although no human studies have shown a negative impact on semen parameters, animal studies have shown damage to testicular sperm cells. There have also been case reports of birth defects in children with paternal exposure to isoretinoin. [Hui EX. Andrology 2022]. It is recommended to stop these medications when a man is trying to conceive. When the female partner is pregnant, it is recommended to use barrier protection (e.g. condoms) due to teratogenic concerns. [Semet M. Andrology 2017]
Herbal Medications / Supplements and male infertility
Herbal medications are widely used in the United States; many people believe that these “natural” remedies have a lower risk of adverse side effects than prescription medications. The use of herbal supplements in men with fertility problems is widespread. A 2004 study looked at 481 men evaluated in an infertility clinic and found that 31 percent of them were taking alternative medications, and that 17 percent of these supplements had clear hormonal activity that was potentially detrimental to sperm production. [Zini A. Urology 2004]
This is not to say that all herbal supplements are necessarily detrimental or provide no beneficial effects on sperm counts and quality. Rather, at this time there are multiple problems with the way that natural supplements are tested, manufactured, and marketed. You may think what you want about vast federal bureaucracies and their inevitable shortcomings and inefficiencies, but the FDA does provide a very powerful and beneficial service in terms of securing a degree of safety and fraud prevention in the manufacture, marketing, and distribution of prescription medications. The days of snake-oil salesmen peddling ineffective and sometimes dangerous homemade remedies are thankfully behind us, at least when it comes to medications requiring a prescription.
Unfortunately, natural supplements do not fall under the jurisdiction of the FDA, and therefore they do not undergo the same intense levels of scrutiny that prescription medications need to pass before being approved for use. The criteria for safety and efficacy testing are much less stringent with natural supplements. When it comes to male fertility, a huge number of alternative treatments, ranging from specific natural supplements to eating more avocados or oysters, have been found by small, uncontrolled studies to potentially be associated with an improvement in semen parameters. In the field of prescription medications, most medications that small uncontrolled studies have suggested may have some positive effects are later shown to not have significant positive outcomes after being tested in the much larger, more rigorous studies required to attain FDA approval. Natural supplements, however, do not have to undergo these larger studies, and therefore claims from these small initial studies are rarely proven or disproven. These small studies also do not produce the same kind of safety data seen with larger, more rigorous studies.
The other problem with a lack of FDA oversight is that the manufacturing process is much less stringently regulated for nonprescription substances. Therefore, purity and amounts of active ingredient can vary significantly between products from different manufacturers. Another alarming trend is the undisclosed addition of certain pharmaceutical agents into allegedly “natural” supplements. Sildenafil (Viagra) has been found in supposedly natural nonprescription supplements for erectile dysfunction, for example, and testosterone derivatives have been found in supposedly natural bodybuilding supplements.
In addition, many natural substances (such as root and bark extracts) have not been thoroughly studied and may in fact contain hormonally active chemicals that are actually detrimental to male fertility. The argument can be made that large scientific studies are expensive, and no company is going to spend the money to conduct these studies on natural supplements for which a patent cannot be obtained. I think that there may be a role for government financial support of such studies for particularly promising supplements. However, until larger controlled studies show measurable and reproducible improvements in fertility, I do not feel that these supplements are worth the money or the risk of potentially negative side effects.
A Review of Frequently Used Herbal Supplements for Male Infertility
1) Red ginseng (Panox or Korean)- This is the most commonly used ingredient in men’s sexual health and comes from root of the Panox plant. Studies have shown some positive impact on erectile dysfunction, possibly through its impact on nitric oxide levels. Though information is scarce, a review of the literature did show some improvements in sperm density, motility, and morphology in 2 small studies. [Kulchakulla M. JUrol 2019]. In terms of safety, concerns of hypoglycemia have been mentioned with the use of ginseng, so care should be taken in men with diabetes. [Cui T. JSexMed 2015]
2) Ashwagandha extract (Withania somnifera)- This is a traditional Indian treatment for infertility and erectile dysfunction. There is some evidence in rat studies of reductions in oxidative stress as well as improvements in the function of seminiferous tubules in rats. [Ambiye VR. EvidBasedComplAltMed 2013]. Two small studies have shown improvements in semen parameters with the use of Ashwagandha. [Kuchakulla M. JUrol 2019]
3) Pine bark (Pycnogenal)- This supplement is made from the French maritime pine tree bark extract and is felt to have antioxidant properties. One small study showed that taking 200mg daily showed some improvements in semen parameters. [Kuchakulla M. JUrol 2019]
4) Shuddha shilajit- Another traditional Indian medicine, this substance is found on the rocks of the Himalayan mountains and is derived from the slow breakdown of plant material. There are questions of antioxidant and anti-inflammatory effects as well as a possible increase in testosterone levels. There is one small study showing increases in sperm density with the use of this supplement. [Kuchakulla M. JUrol 2019]
5) Tribulus terrestris- This supplement is derived from a common low growing vine and is often marketed as a “testosterone booster”. Increased testosterone levels have been reported in animal studies. [Cui T. JSexMed 2015]. However, a randomized double-blind trial in men found no change in testosterone levels with its use. [Santos CA. ActasUrolEsp 2014]. Case reports of kidney and liver toxicity have been reported when used in high doses in young men. [Cui T. JSexMed 2015]
6) Horny goat weed- This supplement is made from an extract of the epimedium plant found in Asia and Southern Europe. Commonly used for erectile dysfunction, this supplement contains small amounts of icariin which is felt to have effects similar to PDE-5 inhibitors (like sildenafil). While improvement erectile function has been found in rats, no evidence of improvements in ED have been yet shown in studies on humans. [Cui T. JSexMed 2015]
7) Fenugreek (trigonella foenum graecum)- This supplement is felt to contain certain sex hormone precursors as well as impact estrogen receptors. [Cui T. JSexMed 2015]. A double-blind placebo controlled study showed improvements in libido while testosterone and prolactin levels stayed within the normal range. [Steels E. PhytotherRes 2011]
8) Maca- This supplement is derived from the root of the Maca plant found in the region of the Andes mountains. Although there is minimal evidence in humans, mice studies have shown improvements in sexual function and semen parameters. [Cui T. JSexMed 2015].
9) DHEA (dehyrdoepiandosterone)- DHEA is a weak prohormone produced by the adrenal gland. It is converted to testostosterone and estradiol in the peripheral tissues of the body. [Cui T. JSexMed 2015]. Since it is an exogenous androgen, it should not be used in men trying to conceive.
10) Ginkgo biloba- Derived from Ginkgo (or maidenhair) tree, this supplement has been used in the treatment of erectile dysfunction. It has been proposed to influence nitric oxide metabolism but there is not currently good evidence supporting its use. [Cui T. JSexMed 2015]. Associated toxicity includes potential headaches and bleeding problems. In the lab, high concentrations of this supplement have been associated with decreases in sperm motility. [Ondrizek RR. Andrology 1998]
11) Yohimbine- Derived from the yohimbe tree in Africa, Yohimbine is commonly used as a treatment for erectile dysfunction. There is some evidence that this supplement can impact nitric oxide metabolism and may be superior to placebo in the treatment of erection problems. [Cui T. JSexMed 2015]. Potential side effects include headaches, sweating, hypertension, insomnia, and agitation.
12) Saw palmetto- An herbal supplement made from the berries of the Serenoa repens plant, this supplement is commonly used for the treatment of BPH (benign prostatic hypertrophy). and its mechanism of action is felt to be similar to that of 5-alpha reductase inhibitors. Laboratory studies subjecting sperm to high levels of saw palmetto were noted to have a negative impact on sperm motility. [Ondrizek RR. Andrology 1998]
13) St John’s Wort- A supplement from the flowing plant Hypericum perforatum, St John’s wort is sometimes used for depression. Studies on sperm exposed to St John’s wort in the lab showed significant decreases in motility. [Ondrizek RR. JAssistReprodGenet 1999]
Summary of Herbal Supplements for Male Infertility
There is no solid evidence to date that any herbal supplement helps significantly with semen parameters and fertility potential in men. A few small studies show that Ashwagandha extra, red ginseng, pine bark extract, and Shuddha shilajit may have the potential to improve semen parameters, but the evidence is not strong enough to recommend their use at this time. Larger randomized trials are clearly needed to define the role of herbal supplements in the management of male infertility.