Andropause part 7 - Treating & Counteracting Andropause

Welcome to part 7 of the ODX Andropause & Low T Syndrome Series. Once Andropause or Low T Syndrome and its causes have been identified, approaches to treatment include testosterone replacement therapy, non-hormonal natural medicine approaches, and lifestyle changes.

Andropause - How Do We Treat & Counteract Andropause?

Dicken Weatherby, N.D. and Beth Ellen DiLuglio, MS, RDN, LDN

The ODX Male Andropause Series

1. Andropause Part 1 – An Introduction
2. Andropause Part 2 – Biology & Physiology
3. Andropause Part 3 – How to identify it
4. Andropause Part 4 – Lab Assessment and Biomarker Guideposts
5. Andropause Part 5 – Clinical Determination
6. Andropause Part 6 – Lab Reference Ranges
7. Andropause Part 7 – How do we treat and counteract andropause?
8. Andropause Part 8 – Lifestyle approaches to addressing Andropause
9. Andropause Part 9 – Optimal Takeaways
10. Optimal The Podcast – Episode 9: Andropause

Testosterone and hormonal therapy in andropause

Fortunately, testicular transplants are a thing of the past once testosterone was identified and made available in oral, transdermal, and intramuscular forms.[i]

Testosterone replacement tends to be the go-to treatment for symptomatic LOH and persistently low T once a full clinical workup is completed. Indiscriminate use of testosterone therapy is discouraged.

Endocrine Society guidelines for testosterone therapy emphasize reserving the diagnosis of hypogonadism for symptomatic men with consistently low fasting morning serum T levels.[ii] It is important to rule out other causes of symptoms and assess for acute conditions that may reduce T levels temporarily.

Provision of exogenous T reduces the pituitary release of FSH and LH leading to inhibition of testicular production of testosterone. This may have an effect on spermatogenesis and fertility.[iii]

As with any pharmaceutical or hormone treatment, Initiation of testosterone therapy should be a joint decision between patient and physician. The determination to go ahead should be fully informed, including a review of potential risks and benefits.

The goal of testosterone therapy should be to maintain serum T within an optimal range. Restoring testosterone to levels found in “young men” reportedly induces a sense of well-being, enhances physical performance, and restores sex drive in some men.[iv] [v]

Research confirms that increases in serum testosterone associated with T therapy positively correlate with improvements in quality of life, strength, physical function, body composition, mood, vitality, and overall well-being. [vi]

Though the CDC ranges for T are broad at 303-852 ng/dL (10.5-29.5 nmol/L),[vii] maintenance at the mid to upper range may be prudent and can be adjusted according to symptomology.

Testosterone replacement is available in several forms:[viii]

• Tablets
• Patches
• Gels
• Implants
• Injections

In a randomized controlled trial of 39 men 50-70 years of age, testosterone gel therapy was found to improve body composition by significantly increasing lean body mass and significantly decreasing body fat mass in men with type 2 diabetes and bioavailable T levels of less than 210 ng/dL (7.3 nmol/L). Total, bioavailable, and free T increased and SHBG decreased during the 24 week study period.[ix]

Proceeding with caution

Androgens stimulate prostate tissue, warranting the recommendation for periodic assessment of PSA (labs) and benign prostatic hyperplasia/BPH (digital rectal exam).[x]

Serum testosterone and hematocrit levels, symptoms, adverse effects, and prostate cancer risk evaluation should be conducted during the first year of therapy.[xi]

Subsequent monitoring is indicated to ensure efficacy and rule out adverse effects:[xii]

• Assess PSA prior to therapy, 3-6 months following initiation, and assess regularly according to guidelines for prostate cancer screening.
  • If PSA increase above 1.4 ng/mL within the first year of testosterone therapy, obtain a urology consult.
• Maintain testosterone ~mid-normal range, assess 3-6 months after initiation
• Assess hematocrit 3-6 months after initiation and then annually. Hold testosterone if hematocrit rises above 54% and re-evaluate before restarting therapy.
• Evaluate bone mineral density 1-2 years after testosterone initiation
• Benefits may include
  • Decreased fat mass, increased muscle mass and strength
  • Reduced risk of metabolic and cardiovascular dysfunction
  • Improved insulin sensitivity
  • Increased erythropoiesis, hemoglobin, and reticulocyte count
  • Possible improvement in bone mineral density of the lumbar spine
  • Possible improvements in cognitive function and mood
  • Improvements in libido and sexual satisfaction
  • No conclusive evidence that testosterone therapy increases risk of benign prostatic hypertrophy or prostate cancer, though these should be ruled out prior to initiation

Testosterone therapy is contraindicated in those with[xiii] [xiv] [xv] [xvi] [xvii]

• Benign prostatic hyperplasia, severe or symptomatic
• Breast cancer
• Cardiac disease
• Congestive heart failure (uncontrolled)
• Elevated hematocrit
  • Greater than 48% at baseline
  • Greater than 50% if living at high altitude
  • 54% or greater during T therapy
• Hypertension, severe, uncontrolled
• International Prostate Symptom Score (IPSS) greater than 19
• Myocardial infarction or stroke (within past six months)
• Polycythemia
• Prostate cancer
• Prostate nodule or induration
• Prostate specific antigen level greater than 4 ng/mL or greater than 3 ng/mL in those at increased risk for prostate cancer without further workup
• Prostate symptomatology
• Sleep apnea, untreated
• Thrombophilia
• Urinary tract symptoms (severe)

Testosterone therapy [xviii] [xix] [xx] [xxi] [xxii] [xxiii]

Targets for T therapy vary between professional groups [xxiv]

Testosterone therapy summary. [xxv] [xxvi]

• Avoid T therapy if any contraindications are present
• Natural preparations should be used, avoiding synthetic androgens
• Initiate therapy with short‐acting (transdermal, oral, buccal) versus long‐acting (intramuscular, subdermal) preparations
• Monitor red blood cell parameters, PSA, and digital rectal examination at 3, 6, and 12 months and then annually
• Monitor for progress and for development of contraindications

Aromatase inhibitors

The use of aromatase inhibitors (AIs) in the treatment of low testosterone has been studied as well. Aromatase inhibitors reduce the conversion of testosterone to estradiol and may help preserve serum levels of testosterone. However, drawbacks related to bone density must be considered.

Randomized, double-blind, placebo-controlled trials indicate that both transdermal T and aromatase inhibitors can help restore serum TT from below 350 ng/dL (12.2 nmol/L) to a mean of 473 ng/dL (16.4 nmol/L or above. However, research suggests that the aromatase inhibitor may be associated with a decrease in lumbar bone mineral density, highlighting the importance of estradiol to bone health.[xxvii] [xxviii]

A 12-month randomized double-blind placebo-controlled trial of men aged 65-82 years who had a TT below 350 ng/dL (12 nmol/L) demonstrated[xxix]

• Both 5 grams of transdermal testosterone gel and 1 mg of anastrozole aromatase inhibitor increased serum testosterone to greater than 500 ng/dL (17 nmol/L).
• An increase in lean body mass was seen in both treatment groups but the increase was only significant in the AI group.
• Lumbar spine BMD increased in the testosterone and the placebo groups but did not increase in the AI group.
• Researchers assert that conversion of testosterone to estradiol is vital to skeletal health.
• Increased BMD in the placebo-group was attributed to supplementation with calcium and vitamin D that all participants received.

HCG

Human chorionic gonadotropin (HCG) is being explored as a therapeutic option in LOH. HCG appears to support testicular function including fertility, production of testosterone and

insulin-like factor 3, and hydroxylation of vitamin D. A 6-month trial of HCG versus T therapy in LOH revealed positive effects of HCG on 25(OH)D, estradiol, prostate volume, and hematocrit. Larger clinical trials are recommended.[xxx]                

Optimal Takeaways for treating/counteracting Andropause / Low T syndrome / LOH

Testosterone therapy should be based on clinically confirmed LOH and monitored closely for adverse reactions or contraindications.

• Exogenous testosterone may inhibit testicular production of T and affect spermatogenesis and fertility.
• Risks and side effects of T therapy must be reviewed with clients.
• Restoration of T to levels found in young men may promote significant improvements in physical function, body composition, and quality of life.
• A trial of T therapy is indicated if[xxxi]
  • Total T is 230-345 ng/dL (8-12 nmol/L)
  • Free T is less than 65 pg/mL (225 pmol/L)
• Testosterone therapy is likely indicated if
  • Total T is 231 ng/dL (8 nmol/L) or less
  • Free T is 52 pg/mL (180 pmol/L) or less
• Use of aromatase inhibitors may help preserve serum T but reduce bone mineral density due to decreases in estradiol.

NEXT UP: Andropause Part 8 – Lifestyle Approaches to Address Andropause

Research

[i] Nieschlag, E. “Late-onset hypogonadism: a concept comes of age.” Andrology vol. 8,6 (2020): 1506-1511. doi:10.1111/andr.12719 [R]

[ii] Singh, Parminder. “Andropause: Current concepts.” Indian journal of endocrinology and metabolism vol. 17,Suppl 3 (2013): S621-9. doi:10.4103/2230-8210.123552. [R]

[iii] Braga, Patrícia C et al. “Late-onset hypogonadism and lifestyle-related metabolic disorders.” Andrology vol. 8,6 (2020): 1530-1538. doi:10.1111/andr.12765 [R]

[iv] Demers, Laurence M. “Andropause: an androgen deficiency state in the ageing male.” Expert opinion on pharmacotherapy vol. 4,2 (2003): 183-90. doi:10.1517/14656566.4.2.183 [R]

[v] Guidelines on the management of sexual problems in men: the role of androgens A statement produced by: British Society for Sexual Medicine. 2010. [R]

[vi] Gunnels, Trint A., and Richard J. Bloomer. "Increasing circulating testosterone: impact of herbal dietary supplements." Journal of Plant Biochemistry & Physiology (2014). [R]

[vii] Bhasin, Shalender et al. “Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline.” The Journal of clinical endocrinology and metabolism vol. 103,5 (2018): 1715-1744. doi:10.1210/jc.2018-00229 [R]

[viii] NHS. The ‘male menopause’ 2019. [R]

[ix] Magnussen, L V et al. “Testosterone therapy preserves muscle strength and power in aging men with type 2 diabetes-a randomized controlled trial.” Andrology vol. 5,5 (2017): 946-953. doi:10.1111/andr.12396 [R]

[x] Rogers, Linda C. "The role of the laboratory in diagnosing andropause (male menopause)." Laboratory Medicine 36.12 (2005): 771-773. [R]

[xi] Bhasin, Shalender et al. “Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline.” The Journal of clinical endocrinology and metabolism vol. 103,5 (2018): 1715-1744. doi:10.1210/jc.2018-00229 [R]

[xii] Singh, Parminder. “Andropause: Current concepts.” Indian journal of endocrinology and metabolism vol. 17,Suppl 3 (2013): S621-9. doi:10.4103/2230-8210.123552. [R]

[xiii] Bhasin, Shalender et al. “Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline.” The Journal of clinical endocrinology and metabolism vol. 103,5 (2018): 1715-1744. doi:10.1210/jc.2018-00229 [R]

[xiv] Corenblum, Bernard. "Could this man have andropause?." Canadian Journal 107 (2004). Continuing Medical Education.[R]

[xv] Huhtaniemi, Ilpo, and Gianni Forti. “Male late-onset hypogonadism: pathogenesis, diagnosis and treatment.” Nature reviews. Urology vol. 8,6 335-44. 19 Apr. 2011, doi:10.1038/nrurol.2011.47 [R]

[xvi] Lawrence, Kristi L et al. “Approaches to male hypogonadism in primary care.” The Nurse practitioner vol. 42,2 (2017): 32-37. doi:10.1097/01.NPR.0000511774.51873.da [R]

[xvii] Giagulli, Vito Angelo et al. “Critical evaluation of different available guidelines for late-onset hypogonadism.” Andrology vol. 8,6 (2020): 1628-1641. doi:10.1111/andr.12850 [R]

[xviii] Bhasin, Shalender et al. “Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline.” The Journal of clinical endocrinology and metabolism vol. 103,5 (2018): 1715-1744. doi:10.1210/jc.2018-00229 [R]

[xix] Swee, Du Soon, and Earn H Gan. “Late-Onset Hypogonadism as Primary Testicular Failure.” Frontiers in endocrinology vol. 10 372. 12 Jun. 2019, doi:10.3389/fendo.2019.00372 [R]

[xx] Singh, Parminder. “Andropause: Current concepts.” Indian journal of endocrinology and metabolism vol. 17,Suppl 3 (2013): S621-9. doi:10.4103/2230-8210.123552. [R]

[xxi] Rao, Amanda et al. “Testofen, a specialised Trigonella foenum-graecum seed extract reduces age-related symptoms of androgen decrease, increases testosterone levels and improves sexual function in healthy aging males in a double-blind randomised clinical study.” The aging male : the official journal of the International Society for the Study of the Aging Male vol. 19,2 (2016): 134-42. doi:10.3109/13685538.2015.1135323 [R]

[xxii] Ide, Hisamitsu, Mayuko Kanayama, and Shigeo Horie. "Diabetes and LOH Syndrome." Diabetes and Aging-related Complications. Springer, Singapore, 2018. 167-176. [R]

[xxiii] Kalra, Sanjay et al. “Management of late-onset hypogonadism: person-centred thresholds, targets, techniques and tools.” The journal of the Royal College of Physicians of Edinburgh vol. 51,1 (2021): 79-84. doi:10.4997/JRCPE.2021.121 [R]

[xxiv] Giagulli, Vito Angelo et al. “Critical evaluation of different available guidelines for late-onset hypogonadism.” Andrology vol. 8,6 (2020): 1628-1641. doi:10.1111/andr.12850 [R]

[xxv] Nieschlag, E. “Late-onset hypogonadism: a concept comes of age.” Andrology vol. 8,6 (2020): 1506-1511. doi:10.1111/andr.12719 [R]

[xxvi] Giagulli, Vito Angelo et al. “Critical evaluation of different available guidelines for late-onset hypogonadism.” Andrology vol. 8,6 (2020): 1628-1641. doi:10.1111/andr.12850 [R]

[xxvii] Dias, J P et al. “Testosterone vs. aromatase inhibitor in older men with low testosterone: effects on cardiometabolic parameters.” Andrology vol. 5,1 (2017): 31-40. doi:10.1111/andr.12284 [R]

[xxviii] Dias, J P et al. “Effects of aromatase inhibition vs. testosterone in older men with low testosterone: randomized-controlled trial.” Andrology vol. 4,1 (2016): 33-40. doi:10.1111/andr.12126 [R]

[xxix] Dias, J P et al. “Effects of aromatase inhibition vs. testosterone in older men with low testosterone: randomized-controlled trial.” Andrology vol. 4,1 (2016): 33-40. doi:10.1111/andr.12126 [R]

[xxx] Swee, Du Soon, and Earn H Gan. “Late-Onset Hypogonadism as Primary Testicular Failure.” Frontiers in endocrinology vol. 10 372. 12 Jun. 2019, doi:10.3389/fendo.2019.00372 [R]

[xxxi] Jakiel, Grzegorz et al. “Andropause - state of the art 2015 and review of selected aspects.” Przeglad menopauzalny = Menopause review vol. 14,1 (2015): 1-6. doi:10.5114/pm.2015.49998 [R]