Testosterone replacement and the aging male

I recently read the following about testosterone and testosterone replacement  “Last summer I took Bruno, my ten-year-old cairn terrier, to the vet for his annual check-up.  “Wow, he has some energy level for an older dog,” commented my vet as he watched Bruno dart around the exam room. My vet started to examine Bruno. “Aha”, he exclaimed. “He’s intact. That’s why he’s still so quick moving and trim. It’s all that testosterone.”

The Vet’s findings are similar to what we find in men. Adequate testosterone levels benefit the aging male. Over the last ten years, prescriptions for testosterone for men over forty have tripled. Testosterone is essential for maintaining muscle and lean body mass, strength and energy levels, fertility, libido and sexual performance. It is needed to maintain normal bone density and prevent osteoporosis. It also positively impacts cognitive function and mood. Unfortunately for men, testosterone progressively declines as they age. Sometimes to levels low enough to impair the numerous functions listed above, leading to adverse health conditions and significant changes in quality of life. So it is easy to see why healthcare providers and their aging male patients would consider testosterone replacement therapy to reverse symptoms related to low testosterone and restore better quality of life.

Several recent studies, however, indicate that testosterone replacement therapy may not be as beneficial to the aging male as originally thought. We need to consider the balance between the risks and benefits.  Their findings link testosterone replacement therapy to an increase in cardiovascular problems. The New York Times and several other national news outlets ran features last month highlighting the findings of a recent study that showed a correlation between testosterone replacement therapy and increased cardiac risk, setting off a bit of a frenzy over the need to better scrutinize how and to whom this medication should be dispensed. There is also discussion over the need for pharmaceutical companies to put a warning label on testosterone replacement therapies and their relevant advertising material, and for doctors to have patients sign a consent indicating an awareness of the potential side effects of testosterone prior to being prescribed this drug.

So how concerned should you be if you are currently on testosterone replacement therapy, or you are experiencing symptoms of low testosterone and are considering discussing testosterone replacement therapy with your health care provider? Will testosterone replacement therapy increase your risk of having an adverse cardiac event?

The study receiving so much recent media attention was funded by the National Institute of Health (NIH) and was published in the journal PLoS ONE. It found that men over the age of 65 had double the rate of heart attacks within the first 90 days of starting testosterone. Men younger than 65 with a history of heart disease had triple the rate of heart attacks within the first 90 days of starting testosterone. Men younger than 65 with no history of heart disease showed no increased risk of heart attack.  Other studies have also produced similar findings. None of these studies have been able to demonstrate specifically how testosterone is causing adverse cardiovascular incidents. Some are suggesting increased physical activity elicited by the physical improvements gained from testosterone replacement therapy is placing too much stress on the cardiovascular systems of men already at risk. However, if you are over 65 or have a history of cardiovascular disease, testosterone replacement therapy may not be for you.

Another source of concern is the growing number of health clinics that cater to the needs of men interested in extending the vigor and virility of youth into old age with the help of testosterone replacement therapy.  Many of these “male rejuvenation” clinics are billing testosterone as a panacea for all that ails the aging male. These clinics are prescribing testosterone without properly screening for this condition and without properly following up with those patients given prescriptions and refills.  Testosterone replacement therapy benefits many aging men, but it is not for all.  Like all medications, testosterone can pose health risks if prescribed to men who do not need it or have pre-existing conditions that contradict it.

Because of the steep increase in the number of prescriptions being written for testosterone, as well as the number of clinics actively marketing testosterone replacement to aging men, the Endocrine Society updated its clinical practice guideline in 2010 to provide a better protocol for evaluating and treating patients with low testosterone.

If you are currently on testosterone replacement therapy (TRT) or considering seeing a healthcare professional about starting it, your initial and follow-up evaluations should adhere to the Endocrine Society’s guidelines.  A healthcare professional should never, ever prescribe testosterone based solely on a patient having symptoms of low testosterone. Your initial examination should include a serum (blood) sample evaluated by a reference lab using a standardized method for testosterone measurement. Initial blood tests often include a total and free testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), prostate specific antigen (PSA), prolactin, and hematocrit (measurement of red blood cells). The sample should be drawn between 7:00am and 11:00am particularly for men under 50, as testosterone levels are highest in the morning.

Due to the lack of standardization in testosterone measurement there is not a level below which testosterone is considered ‘low’.  However, a total testosterone level below 300 ng/dl is usually considered the lower limit of normal.  If your total testosterone level is low, evaluating hormones secreted by the pituitary, LH and FSH will help your healthcare provider determine if the cause is impaired production in the testes (primary hypogonadism) or a problem with the hypothalamus and/or pituitary (secondary hypogonadism). If secondary hypogonadism is suspected, additional testing should be done to determine the cause. If your total testosterone level is low or borderline-low, bone mineral density should be evaluated with a DEXA scan to determine if you have decreased bone density (eg osteopenia or osteoporosis).

A clinical diagnosis of low testosterone based on symptoms and blood work demonstrating low serum testosterone makes you a good candidate for TRT. However your healthcare provider might not suggest TRT if:

  1. You are 65 years of age and older.
  2. You have a history of cardiovascular disease.
  3. You have prostate cancer or a PSA level above 4 ng/ml. (TRT can stimulate the growth of prostate cancer in men with prostate cancer.)
  4. You have severe lower urinary tract symptoms.
  5. You have who have a history of breast cancer.
  6. You have hematocrit above 50%. (TRT stimulates the production of red blood cells. Excessive levels can cause formation of blood clots.)
  7. You have severe sleep apnea. (Severe sleep apnea might be a sign of cardiovascular disease.)
  8. You are concerned about your fertility. (TRT impairs sperm production in testes.)

Once you have started testosterone replacement therapy, your healthcare provider should monitor your progress. You should be evaluated every three to six months to determine if your symptoms are improving. Your serum testosterone level and several other hormones should be measured, and the goal should be to maintain a testosterone level in mid-normal range (ie, 400 to 600 ng/dl). You should be assessed for any adverse effects (cardiovascular disease, PSA/prostate cancer, hematocrit/erythrocytosis). You bone density should be re-evaluated by DEXA scan every one to two years.  Your healthcare provider should not be refilling your prescription without doing this type of periodic assessment.

Before I end this blog, I want to mention that life style interventions have been shown to improve testosterone levels. Studies show there is a link between obesity and low testosterone. Men who are overweight tend to have lower testosterone levels than men who are normal weight. Weight loss, improved diet, and exercise have been shown to boost testosterone levels.

Testosterone replacement therapy, when prescribed and monitored properly, has been proven to be safe and effective for men over forty with low testosterone. It has been shown to improve energy level, libido, muscle and bone loss, and mood. Studies have shown it can lower blood pressure and blood sugar and can improve cholesterol levels.  Studies also demonstrate that men with normal testosterone levels have a 40% lower death rate compared with men who have low testosterone levels.  If you think you suffer from low testosterone, testosterone replacement therapy could be of great benefit. Just make sure you are evaluated and monitored by a physician who is experienced with hormone replacement therapy in men.

References:

 Bhasin S, Cunningham GR, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010 Jun; 95(6): 2536-2559.

Finkel W, Greenland S, et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLOS ONE. 2014 Jan; DOI: 10.1371.

Brawer MK. Testosterone replacement in men with andropause: an overview. Rev Urol. 2004; 6(Suppl 6): S9-S15.

O’Connor A. New concern about testosterone and heart risks. NYT, Jan 29, 2014.

La Puma J. Don’t ask your doctor about low T. NYT, Feb 3, 2014.

Male menopause: testosterone therapy marketing frenzy draws skepticism. From voxxi.com, Sep 9, 2012.

 

 

 

 

Fertility Preservation and Gender Transition: The Decision to Bank Sperm

The desire to have children is common among individuals transitioning with 38% of respondents of the National Transgender Discrimination Survey indicating they are parents1. A Belgium study surveyed 121 patients transitioning and found that 40% would want children and that half of these would like a biologic child2.  Also in this study, 77% of 101 trans women wanted the professionals treating them to discuss fertility options with 51% stating that they would have cryopreserved sperm, or at least seriously considered this, if it had been discussed.

The World Professional Organization for Transgender Health (WPATH, http://www.wpath.org) first developed the Standards of Care for the Health of Transsexual, Transgender, and Gender Nonconforming People in 1979. However, it wasn’t until 2011 that they introduced specifics on the Reproductive Health needs of transgender people3. In the current WPATH Standards (http://bit.ly/2msEoQl) they recommend that prior to the initiation of therapy fertility preservation options are discussed, even if the person is currently not interested in future fertility.

Ideally, sperm should be collected before hormones are prescribed. However, it is possible in male to female transitioning that stopping feminizing hormones might provide a window to retrieve sperm. Even in the individual who does not have sperm in the ejaculate, or cannot produce an ejaculate, the potential for sperm retrieval and banking is possible with other modalities. Testicular biopsy with banking of tissue excised during the procedure can be used for conception with in vitro fertilization (IVF) couple with single sperm injection (ICSI). In addition, a recent study4 found normal spermatogenesis in 24% of testes removed at the time of sex reassignment surgery for individuals on long term estrogen therapy.  This suggests that banking of testicular tissue may still be possible in 1/4 of patients treated with long term hormonal therapy.  However, it must be noted that 75% of patients treated with long term estrogen therapy did not have sperm in the ejaculate or on biopsy.

At one fertility clinic511 patients were referred for sperm banking between January 2010 and May 2014. Nine of these patients banked sperm for future potential use. During this 52 month period, 1 couple used the stored sperm, which resulted in a pregnancy. It should be noted however, that the mean age of the patients preserving sperm was 26.5 years of age which might account for the low usage rate of the banked sperm during this study. What was interesting in this study is that there was an increase in yearly referrals to their clinic over the 4.3 years they collected data. However, they found that referrals remained low which they postulated was due to both cost of sperm banking as well as lack of awareness that fertility preservation was an option.

Unfortunately, the reproductive needs of transgender individuals are still largely unmet6. Hopefully, this will be changing as more health professionals provide much needed information on reproductive health to individuals undergoing gender transitioning.

References:

  1. James SE, Herman JL, Rankin S, Keisling M, Mottet L, Anafi M. 2015 U.S. Transgender Survey. December 2016:1-302.
  2. De Sutter P, Kira K, Verschoor A, Hotimsky A. The Desire to Have Children and the Preservation of Fertility in Transsexual Women: a Survey. International Journal of …; 2002.
  3. Coleman E, Bockting W, Botzer M, et al. Standards of Care for the Health of Transsexual, Transgender, and Gender-Nonconforming People, Version 7. International Journal of Transgenderism. 2012;13(4):165-232. doi:10.1080/15532739.2011.700873.
  4. Schneider F, Neuhaus N, Wistuba J, et al. Testicular Functions and Clinical Characterization of Patients with Gender Dysphoria (GD) Undergoing Sex Reassignment Surgery (SRS). The journal of sexual medicine. 2015;12(11):2190-2200. doi:10.1111/jsm.13022.
  5. Jones CA, Reiter L, Greenblatt E. Fertility preservation in transgender patients. International Journal of Transgenderism. 2016;17(2):76-82. doi:10.1080/15532739.2016.1153992.
  6. HUNGER S. Commentary: Transgender People Are Not That Different after All. Cambridge Quarterly of Healthcare Ethics. 2012;21(2):287-289. doi:10.1017/S0963180111000818.

 

Zika virus found inside spermatozoa

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Spermatozoa infected by Zika virus (green; arrowhead)

The Zika virus has been shown to be present in semen for as long as 6 months. However, recent work by Martin-Blondel et al  of the Infectious and Tropical Diseases Department of Toulouse University Hospital are the first to demonstrate the presence of the Zika virus in sperm. What is facinating is that in their index case the “ Zika virus was found to be present in all sperm samples only up to the 37th day. Beyond that point, the virus was found only in the semen, where it persisted for over 130 days.”

 

Implications of this does not change the recommendations for use of a barrier contraceptive however does support the use of washed sperm in in vitro fertilization sooner than 6 months after male exposure to the Zika virus. It also gives more impetus to test sperm donations for the Zika virus in fertility clinics. http://bit.ly/2cYlhrF

ZIKA Alert: Should Men be Banking Sperm?

A Liquid Nitrogen refrigerator containing sperm and eggs samples. High tech lab equipment used in the in vitro fertilization process.

A Liquid Nitrogen refrigerator containing sperm and eggs samples. High tech lab equipment used in the in vitro fertilization process.

As a specialist in male fertility and owner/director of a sperm bank (http://NYCryo.com) , I have been increasingly asked this question by my colleagues and patients over the past several weeks. Interest in the Zika has been ignited recently by news coverage of celebrities including Pau Gasol of the Chicago Bulls talking about freezing his sperm in the Washington post (http://wapo.st/293BkUP) ….if he even decides to go to the Olympic games. In fact, golf greats like Jason Day, Dustin Johnson, Shane Lowry and Rory McIlroy together with Basketball legends LeBron James and Stephen Curry have pulled out of the  games entirely (http://wapo.st/293Cob5, http://wapo.st/29g036u) while others like Jordan Spieth are weighing their options (http://wapo.st/293DG5U). To add to this concern, the Center for Disease Control (CDC) had issued warnings earlier this year on travel for pregnant women and continue to monitor/update their recommendations (http://bit.ly/29ewocX) . In this brief blog I will try to provide a well referenced overview of what is known about the Zika virus to help you decide what is best for you and your future family. A great review article on Zika virus in pregnancy can be found at http://bit.ly/29dWhfn .

 

First the facts provided by the CDC (http://1.usa.gov/294JyZ0) .

  • A man with Zika virus can pass it to his female or male sex partners through their semen….even if they have never had symptoms. In addition, Zika viral RNA level were higher in semen samples then in blood urine or saliva (http://bit.ly/29dkujA) .
  • Using condoms or delaying sex can reduce the risk of getting Zika from sex…however it is not known where saliva or vaginal fluids can pass the virus on.
  • Zika virus RNA has been detected in semen up to 62 days after the onset of symptoms (http://bit.ly/299BJBd) . CDC therefore recommends that men who have been diagnosed with Zika should consider using condoms or not having sex for at least 6 months.

 

It is clear from these statements that we need to know much more about how the Zika virus. In particular, how the virus is transmitted and even more about the longevity of the virus in the human host. So how should men interested in their future fertility protect themselves? Should they bank their sperm as Pau Gasol believes one should? That question is not a simple one to answer given the paucity of data presently available on the Zika virus. Many questions remain before a definitive answer can be given. In fact, there are more questions then there are answers.

  1. Should all pregnant couples be screened for the Zika virus and what exactly should be tested? One problem is that not also tests are as sensitive and many correctly performed tests yield incorrect results (http://n.pr/299L93j) .
  2. What are the best methods to test for the ZiKa virus (http://bit.ly/29kyR9s) ? There are most sensitive test is the Reverse Transcription-Polymerase Chain Reaction which tests for the presence of a piece of the virus. However, it is only positive for 1 to at most 4 weeks after the virus is in the host. The Zika MAC-ELISA is a better test which detects the virus for up to 12 weeks after exposure. However, the possibility still exists that the virus is present after this time but just not detectable.
  3. Should pregnant women have screening during pregnancy and if so at what frequency? Although there are recommendations for screening during pregnancy (http://bit.ly/29kyyeT) who to handle positive results is still evolving.
  4. Does screening guarantee the absence of virus RNA (http://bit.ly/29kyR9s) ? The answer is no. In addition, since screening is usually done on symptomatic individuals and the Zika virus can be asymptomatic in a large number of men, we would need to screen all men considering conceiving with their partner…which is not practical or even possible.
  5. What fluid type should be screened? Cerebrospinal fluid, blood, urine, saliva and semen all seem to have the virus in them…however, which is the best to test is not yet known.
  6. Does the virus directly affect the sperm or egg cell or the genetic material in these cells is also not yet known. However the FDA has imposed restrictions (http://bit.ly/29p4fAF)  on the freezing of sperm and eggs (oocytes) from men and/or women that have had:
    1. A diagnosis of Zika in the past 6 months
    2. A residence, in or travel to, an area with active Zika transmission within the past 6 months
    3. Sex within the past 6 months with a partner who is known to have lived, traveled, or has been diagnosed with Zika in the past 6 months?

 

Men have been banking sperm prior to therapy that might affect their fertility as well as a protection form hazards to their reproductive health from their occupation. It is therefore entirely appropriate for them to bank sperm prior to travel to an area known to have the Zika virus. However, as discussed above, even if they undergo testing for the Zika virus prior to freezing sperm there is no guarantee that the specimen stored is free of the virus from possible prior exposure. In addition, sexual relations with their partner anytime during the 6 months after their return from an area endemic for the Zika virus might predispose their partner to the infection. No easy answers at this time…..just more questions.