Exogenous Androgens / Anabolic Steroids and Male Infertility
Introduction to the Impact of Exogenous Androgens / Anabolic Steroids on Sperm Numbers and Quality
Hypogonadism (low testosterone, or “low T”) is a common problem that is being increasingly diagnosed by the medical community, primarily due to an increased awareness of the problem. Some studies have shown that as many as 20 percent of men being treated for fertility issues have hormone problems such as low testosterone. Normalization of testosterone levels can potentially result in improvements in energy, libido, sexual function, and fertility. However, the types of hormonal treatment that a man chooses to use can have a dramatic impact on his fertility.
Terminology note: the word “androgen” refers to any substance or compound which has male hormonal activity. Testosterone is a common androgen.
When a man has low testosterone levels, there are two ways in which they can be increased:
1 )Exogenous androgen replacement
Exogenous replacement in when androgens are given through pills, patches, gels, injections, or pellets
2) Increased endogenous production
Increased endogenous production involves giving a medication that causes the man’s own testicles to increase their production of testosterone. Medications such as clomiphene, anastrazole, and HCG cause increased endogenous production of testosterone. See the "Low Testosterone" section of this website for more information on these medications.
Both of these approaches effectively increase blood testosterone levels. However, sperm production is dependent upon high testosterone levels within the testicles, not just in the bloodstream. Therefore, if a man is trying to have a child, medications that increase endogenous testosterone production should be used. Exogenous androgens, on the other hand, cause the pituitary gland to decrease the release of FSH and LH. Without sufficient FSH and LH, testicular production of testosterone and sperm dramatically decreases, with significant negative implications for male fertility.
Exogenous androgens come in four basic types:
1) Prescription testosterone replacement therapy
2) Anabolic steroids
3) Prohormones
4) T boosters.
Prescription Testosterone Replacement
Over the last decade, there has been a significant increase in awareness and treatment of low T in men. Many people are now aware that certain aging-related problems in men, such as decreased libido, erectile dysfunction, decreased lean body mass, and osteoporosis, are associated with decreased testosterone levels and are at least partially reversible with testosterone replacement therapy. Between 2008 and 2013, there was a 170 percent increase in testosterone prescriptions written in the United States. Most of these prescriptions are for older men in whom fertility is not a concern. However, as part of this trend of increasing usage, more young men are being prescribed exogenous T replacement as well, typically without the doctor knowing of its significant negative impact on male fertility. Most men who receive exogenous T replacement wind up with sperm counts of under 1 million sperm per cc after just three to four months of therapy.
Types of Androgen Replacement
Side effects of prescription testosterone include:
1) Acne
2) Gynecomastia (breast enlargement)
3) Fluid retention
4) Sleep apnea (though not all experts agree on this)
5) Testicular atrophy
6) Erythrocytosis (increase in red blood cells as a percentage of total blood volume; can make the blood more viscous and lead to
heart attack or stroke)- see "Erythrocytosis/Polycythemia" section for more detailed information.
Anabolic Steroids
Anabolic steroids are androgens that are particularly effective at increasing muscle and bone mass. They accomplish this by promoting protein metabolism and storage.
There are some legitimate medical uses for anabolic steroids, including the treatment of anemia and to reverse protein loss in patients who have prolonged immobilization following severe illness, trauma, or surgery. Anabolic steroids are also used for appetite stimulation and maintenance of muscle mass in patients with diseases such as cancer and AIDS.
Most commonly, however, anabolic steroids are used illicitly by bodybuilders and athletes to increase muscle mass and strength, and also by athletes to help speed their recovery following sports-related injuries. Some take oral forms, such as oxymetholone (Anadrol), oxandrolone (Anavar, Oxandrin), stanozolol (Winstrol), or methandrostenolone (Dianabol, also called “Dbol”). Others use injections of nadrolone decanoate (Deca-Durabolin, also called “Deca”), nandrolone phenpropionate (Durabolin), or Boldenone undecylenate (Equipoise). There’s also an ointment form, tetrahydrogestrinone (known as THG, “the cream,” or “the clear”).
All anabolic steroids, however, still have androgenic hormonal activity as well. Men who abuse anabolic steroids for bodybuilding purposes often take the equivalent of as much as 5,000 mg of testosterone per week, an amount far greater than the body naturally produces. The result is blood testosterone levels than can be up to twenty times higher than what is considered normal. As discussed above, high blood levels of testosterone cause the pituitary gland to decrease the release of FSH and LH, which causes testicular production of testosterone and sperm to drop significantly.
The use of anabolic steroids is banned by all major sports leagues because of the unfair competitive advantage these substances provide. Anabolic steroids are listed as controlled substances, which means that it is technically illegal to possess these substances without a prescription. Production and distribution by non-physicians is also illegal, and therefore most anabolic steroids used for non-medical reasons are manufactured in other countries and smuggled into the United States. This makes quality control and safe manufacturing supervision by such agencies as the FDA not possible.
Anabolic steroid users commonly believe that warnings about the risk of anabolic steroid use are overblown and exaggerated. However, the use of anabolic steroids is associated with many potential side effects, including:
1) High blood pressure
2) Erythrocytosis (increase in red blood cells as a percentage of total blood volume; can make the blood more viscous and lead to
heart attack or stroke)- see the "Erythrocytosis/Polycthemia" link above for more information.
3) Gynecomastia (breast enlargement)
4) Abnormal cholesterol levels
5) Blood sugar control problems
6) Acne
7) Increased male-pattern baldness
8) Increased risk of low testosterone levels later in life
Anabolic steroids have also been linked to an increased risk of coronary artery disease as well as potential direct damage to left ventricular heart function. Liver damage and failure are other serious conditions seen with oral anabolic steroid use. Mood disorders have also been found to be more common in users of anabolic steroids.
It’s estimated that more than a million men in the United States have used anabolic steroids for non-medical reasons at some point. True rates of usage are difficult to determine, as studies have shown that over half of men who use anabolic steroids for non-medical reasons do not tell their physicians they’re using these substances. However, the impact of anabolic steroid use on male fertility is quite clear, with almost all men suffering a significant negative impact on sperm production and quality. It is therefore very important for all men using anabolic steroids to report their use to their fertility doctor if they are trying to conceive.
Prohormones
Prohormones are precursors to androgens. Prohormones have minimal hormone activity themselves, but they are converted by the body’s metabolic processes into active androgens. Interest in prohormones increased following the Anabolic Steroid Control Act of 1990, which made anabolic steroids controlled substances in the United States. Through the use of prohormones such as androstenedione, 4-androstenediol, 1-androstenediol, and 19-norandrostenedione, bodybuilders and athletes found a way to use androgenic compounds legally. In an attempt to close this loophole, the Anabolic Steroid Act of 2004 included prohormones on the list of illegal anabolic steroids.
Since 2004, producers of prohormones have taken several different strategies to keep their products on the market. One (illegal) strategy is to use estrogen derivatives (which are not particularly effective at increasing muscle mass) and illicitly add other undeclared anabolic steroids to these. A second approach is the use of plant-based phytoandrogens (plant substances with androgenic actions), which are currently available over the counter in the United States. Examples of phytoandrogens include triterpenoids and pine pollen. A third approach is through the use of “designer steroids” that are specifically produced to bypass the legal restrictions on anabolic steroids and prohormones, while maintaining androgenic and anabolic actions. Some examples of these designer steroids include Helladrol or H-Drol (4-chloro-17a-methyl-androsta-1,4-diene-3,17-diol), Methastadrol or M-Drol (2a, 17a-dimethyl-etiocholan-3-one, 17b-ol), Epi-MAX (2a, 3a-epithio-17a-methyl-17b-hydroxy-5a-androstane), and 11-OXO (adrenosterone).
Controversy continues to surround prohormones in regards to their legality and effectiveness. From a fertility perspective, however, little controversy exists. The goal of prohormones is to mimic the effects of other exogenous androgens, which have a known significantly negative impact on male fertility.
DHEA
Dehydroepiandrosterone, or DHEA, is a hormone precursor to testosterone that is naturally produced by the body. It was exempted from the Anabolic Steroid Control Act of 2004 due to its designation as an “old dietary ingredient.” It is therefore legally for sale in the United States as a dietary supplement, but its use is banned in organized sports competitions. DHEA has some degree of direct exogenous androgenic activity, and therefore should be avoided in men trying to conceive a child.
T Boosters
T boosters are substances that are supposed to increase the natural production of testosterone by the body. The most common use of T boosters is in men using anabolic steroids who want to promote the return of natural testosterone production between anabolic cycles. Commonly used T boosters include Tribulus terrestris (also known as puncture vine), ginseng (from the Panax genus), and D-aspartic acid (DAA), an amino acid. Examples of commercially available T boosters include Perform, T-Force, Testogen XR, and Testopro, among many others.
T boosters are not regulated by the FDA, and questions remain as to their efficacy and potential mechanisms of action, as most have not been closely studied. The few available controlled studies failed to find an increase in testosterone levels associated with their use, or any improvement in strength. From a fertility standpoint, if they really did enhance endogenous testosterone production, then there should be no detrimental impact on sperm production. However, I recommend that men who are trying to optimize their fertility stop taking T boosters, for two reasons: (1) their production is not regulated by the FDA, so quality control and review of actual ingredients are not under any supervision, and (2) their mechanism of action has not been carefully studied, and therefore certain T boosters may actually have negative hormonal effects on male fertility. For example, ginseng has been shown to contain phytoestrogens, which have female hormonal activity.
Fertility Management of Men Taking Exogenous Androgens
As mentioned earlier, most men taking stronger exogenous androgens—prescription testosterone, anabolic steroids, and some prohormones—see their sperm count drop significantly (oligospermia), and often go to zero (azoospermia), after taking these substances for only three to six months. When they stop taking exogenous androgens, most men will have sperm production return. In some men this may happen as little as three months after the exogenous androgens, but normally it takes four to six months before sperm production resumes, and it can even take two to three years or longer in some circumstances. Some men never regain their prior sperm production capacity, and a minority (5 percent or so) can remain permanently azoospermic. Factors that affect the speed and degree of sperm production recovery include the type and strength of exogenous androgens used, the length of time they were used, and each person’s individual physiologic response. For example, men using transdermal testosterone preparations (patches, gel) tend to require a longer sperm recovery time than men taking testosterone injections.
Men who stop taking exogenous androgens typically experience subsequent low testosterone levels. This can be because their baseline T levels are low (which is why they started taking the androgens in the first place), because their body’s endogenous T production remains suppressed even after going off the exogenous androgens, or both. These men therefore frequently need to be started on medications that increase endogenous testosterone production (such as clomiphene, anastrazole, or HCG), both to improve the hormonal environment for sperm production as well as to decrease the adverse symptoms of low testosterone, such as low energy levels and low libido.
I have found that if a man does not feel terrible after stopping his exogenous testosterone, then he is more likely to continue with the recommended treatment plan to maximize his fertility. That’s why I will often prescribe medications that increase endogenous testosterone production at the same time that the exogenous androgens are stopped. I usually recommend starting with either a higher dose of clomiphene (50 mg daily) or HCG (2000 IU three times per week) and let the patient make the choice between which of these he wants to start with. Clomiphene is cheaper and can be taken by mouth, but it may not increase the testosterone levels quite as much as HCG. HCG involves injections three times a week and is more expensive than clomiphene. Some men do well on just clomiphene, but a substantial majority will need to be switched over to HCG, and they may feel the effects of low testosterone (low energy, etc.) before they make the switch. I typically repeat a hormone profile two weeks after starting a medication or changing doses, and adjust the medications and dosages as necessary, while also taking into consideration the patient’s symptoms. I check a semen analysis three months after the hormone levels have normalized.
For detailed information on endogenous testosterone replacement therapy, see the "Low Testosterone" section of this website.
Can Men Who Want to Have Children Ever Take Exogenous Androgens?
In couples where the man has stopped taking exogenous androgens and the wife becomes pregnant, a common question is whether he can restart taking exogenous androgens if they want to have more children in the future. Emerging scientific evidence suggests that he should stay off all exogenous androgens while he is still interested in conceiving children. When men use exogenous androgens intermittently, their sperm production typically rebounds each time they are “off cycle”—but often sperm numbers and quality do not recover to the same baseline levels that they had prior to restarting the exogenous androgens. This progressive decrease in sperm quality can impair a couple’s future fertility chances, so it is best to stick with increased endogenous production alone until the couple’s fertility efforts are complete.
Some men are very reluctant to stop exogenous testosterone therapy (for example, professional bodybuilders). I think that if the couple really wants the best chance of conceiving a child, then the man should stop taking exogenous androgens and switch over to medications that increase endogenous T production. However, for men who refuse to stop taking anabolic steroids or other exogenous androgens, there have been some studies that show that being on low-dose HCG at the same time as exogenous androgens may somewhat protect sperm production.
In one study, men were given exogenous testosterone by injection or gel, as well as low-dose HCG injections (500 IU three times per week). The study found that these men were able to maintain elevated intra-testicular testosterone levels on this regimen. Semen parameters were decreased, but no men experienced azoospermia.* Again, these results are preliminary, and clearly sperm counts would likely be optimized by stopping all exogenous androgens, but this type of combined regimen is a potential option for some men who wish to preserve some degree of fertility despite using exogenous androgens.
* T. C. Hsieh, A. W. Pastuszak, K. Hwang, and L. I. Lipshultz, “Concomitant Intramuscular Human Chorionic Gonadotropin Preserves Spermatogenesis in Men Undergoing Testosterone Replacement Therapy,” Journal of Urology 189, no. 2 (February 2013).