Andropause part 5 - Clinical Determination

Welcome to part 5 of the ODX Andropause & Low T Syndrome Series. The clinical determination of andropause must take into consideration the patient’s symptomology and lab values of Total and Free testosterone. As you’ll read in this post, the Functional determination of low T syndrome takes a slightly different approach.

Andropause - Clinical Determination

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

Clinical Andropause is likely if these minimum criteria are met, corroborated by EMAS: [i] [ii] [iii] [iv]

• Three primary sexual symptoms (e.g., erectile dysfunction, morning erection, decreased libido)
• Total testosterone below 320 ng/dL (11 nmol/L)
• Free testosterone below 64 pg/mL (220 pmol/L)

Research suggests that certain thresholds of serum T may be associated with a specific set of symptoms. Results of a cross-sectional cohort study of 434 males aged 50-86 years old identified associations between symptoms and total serum T levels. Results were similar when calculated free T was applied:[v] [vi]

Total testosterone levels of 175 ng/dL (6 nmol/L) or less should be further evaluated using MRI and advanced pituitary hormone assessments to rule out the possibility of organic versus functional hypogonadism.[vii]

Although symptomatology can be significant, the European Male Ageing Study reserves the diagnosis of LOH for sexually-associated symptoms (i.e., decreased libido, poor morning erection, and erectile dysfunction) associated with a TT below 320 ng/dL (11 nmol/L) and a free T below 64 pg/mL (220 pmol/L).

Data from the same study suggests that sexual and physical symptoms may be present when TT is within normal range, but free T was low.

Conversely, when free T was normal and TT was low (presuming low SHBG), sexual and physical symptoms were not present.

Researchers suggest measuring free testosterone in men with conditions associated with altered SHBG and/or TT in the lower 200-400 ng/dL (7-14 nmol/L) range:[viii]

According to the International Society for Sexual Medicine (ISSM) [ix]

• SHBG should be evaluated following an initial low serum T in men who are older or obese.
• Altered SHBG can be anticipated in obesity, diabetes, chronic illness, elderly, especially when TT is in the low to normal range.
• Further evaluation is warranted if SHBG is elevated or if TT is between 230-345 ng/dL (8-12 nmol/L) in symptomatic individuals.
• Assessment of free or bioavailable T will provide valuable information about sufficiency of biologically active T.

In general, free or bioavailable testosterone should be measured when:[x]

• TT is 250-350 ng/dL (8-12 nmol/L)
• SHBG is decreased.
• SHBG is increased. Increased SHBG decreases tissue availability of testosterone.

An epidemiological study of 2,588 men 40-80 years found an association between symptomatic LOH and levels of BAT and SHBG.[xiv]

• Men with LOH and erectile dysfunction had an AMS score of 27 or greater, the level considered positive for LOH.
• Results demonstrated a significant correlation between symptoms and serum levels of SHBG and BAT, but not between symptoms and TT or LH.
• There was an observed decrease in total and free T and an increase in SHBG as age increased.
• Researchers concluded that the strongest predictors of LOH symptoms and erectile dysfunction in this group was BAT and SHBG.

A population-based cross-sectional study of 965 men 40-80 years of age with AMS scores of 27 or greater found those with symptomatic LOH had lower levels of calculated free T, BAT, total cholesterol, and triglycerides, Levels of SHBG were significantly higher with a suggested 4.99 ug/mL (44.4 nmol/L) cutoff for diagnosing LOH in symptomatic individuals:[xv]

The Hypogonadism in Males (HIM) study found that 38.7% of men 45 years or older had a TT of less than 300 mg/dL. Results indicated significant differences in SHGB, total, free, and bioavailable T in those with TT less than 300 ng/dL (hypogonadal) and those with TT of 300 ng/dL (10.4 nmol/L) or greater. Risk of hypogonadism increased 17% for every 10-year increase in age:[xvi]

Cutoff values for TT, free T

Different societies have proposed various cutoffs for the diagnosis of LOH[xvii]

NEXT UP: Andropause Part 6 – Lab Reference Ranges

Research

[i] Wu, Frederick C W et al. “Identification of late-onset hypogonadism in middle-aged and elderly men.” The New England journal of medicine vol. 363,2 (2010): 123-35. doi:10.1056/NEJMoa0911101

[ii] 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

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

[iv] 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

[v] Zitzmann, Michael et al. “Association of specific symptoms and metabolic risks with serum testosterone in older men.” The Journal of clinical endocrinology and metabolism vol. 91,11 (2006): 4335-43. doi:10.1210/jc.2006-0401

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

[vii] 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

[viii] 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

[ix] 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

[x] Karakas, Sidika E, and Prasanth Surampudi. “New Biomarkers to Evaluate Hyperandrogenemic Women and Hypogonadal Men.” Advances in clinical chemistry vol. 86 (2018): 71-125. doi:10.1016/bs.acc.2018.06.001

[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

[xii] Karakas, Sidika E, and Prasanth Surampudi. “New Biomarkers to Evaluate Hyperandrogenemic Women and Hypogonadal Men.” Advances in clinical chemistry vol. 86 (2018): 71-125. doi:10.1016/bs.acc.2018.06.001

[xiii] 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

[xiv] Liang, GuoQing, et al. "Serum sex hormone-binding globulin and bioavailable testosterone are associated with symptomatic late-onset hypogonadism complicated with erectile dysfunction in aging males: a community-based study." American Journal of Translational Medicine 2018.

[xv] Liang, Guoqing et al. “Serum sex hormone-binding globulin is associated with symptomatic late-onset hypogonadism in aging rural males: a community-based study.” Sexual health, 10.1071/SH20201. 15 Mar. 2021, doi:10.1071/SH20201

[xvi] Mulligan, T et al. “Prevalence of hypogonadism in males aged at least 45 years: the HIM study.” International journal of clinical practice vol. 60,7 (2006): 762-9. doi:10.1111/j.1742-1241.2006.00992.x

[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