By: Zane Basrawala, MD, FACS
Urology Specialists of the Carolinas
There has been a recent surge in awareness regarding testosterone deficiency. In fact, it seems difficult to go for a couple of days without exposure to a commercial or newspaper ad containing information about low testosterone (“Low T”) and its associated symptoms. As a result, in my practice and with my colleagues at Urology Specialists of the Carolinas, we are seeing many more inquiries from men about testosterone deficiency. Judging by referral patterns, this seems to be the trend at the primary care level as well. This increased popularity in this topic is not unfounded as half a million men per year will be diagnosed with low T levels in their Fifth, Six and Seventh decades of life. (1) Since, this topic is usually well understood amongst our Primary Care and Endocrine colleagues, I wanted to use this article to relay issues that we see specifically with testosterone replacement therapy as it relates to urologic issues.
1) What type of patients do we (as Urologists) typically see regarding hypogonadism and T replacement?
A typical patient comes to us unreferred with classic symptoms of low T such as erectile dysfunction (ED), low libido, decreased energy, decreased muscle mass and mood swings. As expected, a number of referred patients will come in the chief complaint of ED and upon screening will have symptoms and lab values consistent with low T. A more unique and complicated scenario presents with a patient with low T and an elevated PSA (prostate specific antigen). Another unique scenario presents with infertile patients that have low T. Finally, because certain prostate cancers are treated by hormonal therapy (or castration), we find ourselves managing medically induced hypogonadism amongst our own patients.
2) What is a standard evaluation in the work up for a patient suspected of hypogonadism and eligibility for testosterone replacement?
In my practice, I will take patients through a series of basic questions regarding classic low testosterone symptoms. In addition, I search for possible etiologies for low T including testicular insults (testes cancer, mumps, trauma, undescended testis), pituitary dysfunction, medical (anabolic steroids, chronic opiote usage, estrogens, chemo/radiation, prostate cancer hormonal manipulation) and metabolic syndrome.
The physical exam will focus on any obvious neurological defects including visual fields (to rule out pituitary lesions), genitourinary exam with specific attention to testes mass, size and consistency (to rule out causes of primary testes failure). Patients with metabolic syndrome may present with a visceral type obesity. Finally, a digital rectal exam and breast exam will be important to rule out prostate and breast cancer.
Laboratory evaluation is critical. Because of circadian rythems, a T level in the morning is ideal. As we age, this variation is less marked and fluctuation will be seen less in older patients. I will often times initially get a T level in the morning. If this is abnormal, then I will get another T level (ideally around the same time as the first) along with a free T, FSH, LH and prolactin (to rule out secondary causes). If T replacement is considered, then a PSA and CBC are needed to rule out prostate cancer, polycythemia and most practically to get a baseline before starting therapy.
Many men will complain of low energy, low libido and ED but have absolutely normal T levels. This is why I stress to all patients with these symptoms that proper rest , diet, exercise and reducing stress are of critical importance to improving the above symptoms with or without low T. Smoking cessation and normal weight should go without saying but of course we know how important it is to actually say it to our patients!
3) What are the main considerations before starting T replacement therapy?
I find patients to be appropriately concerned about potential side effect regarding testosterone replacement and thankfully, few seem to take this lightly. I will review the risks of uncovering an occult prostate or breast cancer while replacing testosterone. I stress that replacement doesn’t CAUSE these diseases. If patients have a history of polycythemia, fluid overload, CHF or sleep apnea, I will often enlist the help of a cardiologist or primary care provider to get these disorders “tuned up” as much as possible. I have had these physicians communicate that risks outweigh benefits and T replacement is put on hold.
Because families are delaying childbirth, it is not uncommon for a man attempting to conceive a child to consider T replacement. In a simplistic thought process, testicles make sperm and testosterone. If exogenous T is replaced, spermatogenesis decreases significantly (by a negative feedback loop) and conception is less likely. Central acting agents (Such as HCG) work at the level of the pituitary and are more appropriate in this scenario.
4) How does one choose between different T replacement options?
In choosing between Intramuscular Injections, Patches, Gels and Depot Pellets, I find that patients will help guide me based on cost, lifestyle, previous experiences, and exposure to children.
In general, I try to steer patients away from Intramuscular Injections since this doesn’t replicate natural testosterone ryhtems with a high surge of levels and coming down quickly in 2-4 weeks. The need for an injection and the fact that these injections are repeated every 2-6 weeks also make this less desirable. With that being said, this is still a popular means of replacement because of its low cost and high reproducibility. A Patch is a reasonable approach but I have seen poor compliance due to irritation. There are multiple Gel formulations on the market and these seem to do well from a steady state approach. However, the FDA has placed a black box warning on all gels regarding unknown effects when exposed to young growing children. In addition, gels seem to be the costliest option. Compliance and poor absorption also can be problematic. Pellets are easily placed in the subcutaneous fat around the hip with a 10 minute office procedure. These are meant to release over 4 to 6 months. Cost is reasonable compared to gels over this time period and compliance is obviously not an issue. Soreness and small rates of infection seem to be its drawback. I find that patients rarely make it 6 months with normal testosterone levels and repeat pellets placements are needed at 4 and even 3 months on occasion.
5) What is the relationship between Testosterone Replacement and BPH /LUTS (lower urinary tract symptoms)?
Studies have shown that after T replacement, prostate volume did show a slight increase. (2,3). However, other studies have shown flow studies, episodes of retention, post-void residuals and overall voiding symptoms were essentially unchanged (4,5). I personally have found little correlation with worsening of urinary symptoms after initiation of testosterone replacement.
6) What is the relationship between Testosterone Replacement and PSA?
Because prostate epithelial cells make PSA and growth of these cells is driven by T, the relationship between PSA and T replacement has been studied. In general, there seems to be a small increase in PSA levels for the first 3 to 6 months above a patient’s baseline (6). However, the decision for referral and evaluation for elevated PSA should be the same for patients on testosterone replacement compared to those who are not.
7) What is the relationship between Testosterone Replacement and Prostate Cancer?
In the past, a history of prostate cancer was an absolute contraindication to T replacement. However, a recent evaluation of multiple studies revealed very little risk in T replacement in patients treated for prostate cancer (7). A compilation of 147 men in 3 studies showed no significant recurrences greater than expected in men receiving replacement T after successful prostate cancer treatment in the form of surgery, external beam radiation or brachytherapy. When I counsel patients who have been treated for prostate cancer and considering T replacement, I remind them that there are many treated prostate cancer patients with normal endogenous T production. Often times, we just want to get our patients back to this normal T level. Lastly though, studies noted above are small in number and retrospective in nature so caution is still paramount in these cases.
8) What is the role in T replacement and sexual function?
The main benefit of T replacement in sexual function has thought to be its effect on improved libido. However, it also appears from studies that T may enhance the ability of PDE-5 receptors in the corpora cavernosa. Thus, T replacement may work in synergy with PDE-5 inhibitors such as Viagra, Cialis and Levitra for treatment of erectile dysfunction. In my practice, I find that T replacement may aid ED but rarely works as effectively as PDE 5 inhibitors.