Low Testosterone with elevated PSA

[Aaron Hartman]

I have a 76 year old male whose testosterone was 250 and LH=7. So seems like he could use some T, however his PSA is 5.9. I was thinking about using peptide support (maybe CJC/Ipa) but wondered what others would do with this and if they would be worried about the risk for prostate cancer. Of note he is seeing a urologist and had negative biopsy and normal MRI. I also am not considering clomid due to his age but with the LH up a bit wonder if others would consider that.

Thanks

Aaron

[Carl Paige, MD]

Testosterone in prostate cancer. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4647137/

Hypothalamic/pituitary/gonadal axis.  https://www.ncbi.nlm.nih.gov/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&p=PMC3&id=2948422_ijcp0064-0682-f1.jpg

SARMS and BPH.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2098692/

T replacement vs Clomiphene  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5508437/

With LH in normal range but low for his suboptimal T levels clomiphene, enclomiphene may not have a significant impact.  It would be helpful to evaluate his estradiol/estrone levels as they will suppress LH response to low T levels    LH, FSH, DHT levels (blood) and alpha reductase / aromatase assessment would be useful (DUTCH) test to get a more complete picture of  to determine whether T replacement,  hypothalamic (kisspeptin) / pituitary (clomiphene),  estrogen detox support, or possible SARMS would be the most apporpriate management  In any case inform, consent, document, correspondence with urologist should be done for risk management purposes which ever path is choosen

CJC/IPA will enhance T receptors peripherally and overall hormone funciton pletropically and I often use this first before initiating direct T modulation by any of the above then reevaluate labs mentioned and determine best approach.

GH pleitropic effects   https://www.mdpi.com/ijms/ijms-19-00290/article_deploy/html/images/ijms-19-00290-g001.png

Carl

 

[Aaron Hartman]

Carl,

Thanks for the detailed response. Didn’t think about kisspeptin so that is an interesting option in low LH patients. I did get my LH backwards in regards to clomid, thanks for the gentle reminder

Aaron

[Bruce Sloane]

With a negative prostate biopsy I do put this patient on testosterone replacement therapy and monitor the PSA.  If the PSA remains stable or only mildly increases I continue testosterone placement therapy.  If it increases significantly I consider repeat biopsy or observation off TRT. Hope that helps

[Aaron Hartman]

Thanks for the input. I’ll discuss options with him at follow up.

[Claude Fortin]

I have recently reviewed the literature on the subject of TRT in patients with elevated PSA with or without associated prostate cancer. Of note is the estimate that 15% of older men have a nidus of prostate cancer even with normal PSA.

LITERATURE REVIEW OF TRT IN PATIENTS WITH PROSTATE CANCER
There has been a paradigm shift in medical science-based thinking with respect to use of
TRT in patients with a history of prostate cancer. Past dogma was that TRT was contraindicated
in patients with prostate cancer, based on studies by Huggins and Hodges in the 1930s that
showed prostate cancer was influenced by androgens by increasing acid phosphatase, and that
disseminated prostate cancer is inhibited by androgen elimination. This led to surgical castration
as a treatment option for prostate cancer replaced then by ADT (androgen deprivation therapy)
resulting in a lowering of PSA (which replaced acid phosphatase as a biomarker). However, this
way of thinking is outdated.
In more recent years, there have been many studies that acknowledge the negative health
effects and quality of life components of testosterone deficiency (TD), either with or without the
presence of prostate cancer, that respond very well to TRT. (Please see references #1-6 below).
TD is associated with obesity, metabolic syndrome, and sexual dysfunction, adverse cognitive
effects, and headaches to name a few.
It has been demonstrated in more recent medical literature on the subject that higher
endogenous serum androgen concentrations from TRT are not associated with an increased risk
of developing prostate cancer or severity of prostate cancer. (Please see references #7 and 8
below). This is thought to be due to a saturation effect. Young men with peak lifetime
testosterone concentrations rarely have prostate cancer. In fact, low testosterone levels are
associated with higher-grade prostate cancer. The risk of developing prostate cancer is actually
higher in TD patients without TRT (Please see references #9-11 below). 15% of men with TD and
normal PSA (<4 ng/ml) have biopsy-detectable prostate cancer in one study. (Please see
reference #12 below). A Study of 13 men with biopsy proved prostate cancer given TRT with 30-
month follow-up showed no upgrading or prostate cancer progression on follow-up biopsy.
(Please see reference #13 below). In fact, low free testosterone levels correlated with cancer
progression in a study of 154 men with surveillance for biopsy-confirmed prostate cancer given
TRT. (Please see reference #14 below). Finally, in biopsy documented prostate cancer, 29 men
with TRT and 96 men without TRT had similar cancer progression rates at 3 years in one study.
(Please see reference #15 below). Thus, current medical science supports that the old way of thinking is incorrect,

and that TRT is appropriate for patients with TD and a history of prostate cancer.

CONSENSUS OPINION OF THE AMERICAN UROLOGICAL ASSOCIATION
A review of this subject at the 2019 annual meeting of the American Urological
Association included the following conclusions:
1. TRT is not associated with increased risk of or severity of prostate cancer. Multiple single
institutional case studies, multi-institutional series, and population-based studies have
failed to find a higher than expected risk of prostate cancer progression or recurrence in
men with prostate cancer.
2. There is no demonstrable risk of adverse oncologic outcomes with TRT even in patients
with high-risk PCA or while on active surveillance. No solid scientific evidence exists to
prove that use of TRT to achieve normal testosterone levels in hypogonadal men with a
history of localized PCA worsens outcomes. Rather, studies show a lower risk of prostate
cancer in TD patients with TRT.
(Please see references 16,17,18 below).

REFERENCES
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Guidelines on male hypogonadism. http://uroweb.org/wp-content/uploads/EAU-
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[Aaron Hartman]

Thanks for this exhaustive and complete response. It is super helpful and encouraging.

Aaron

[Kristelle Reyes]

Claim your CME here: https://earnc.me/sHklFO

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