Andropause part 3 - How Do We Identify It?

Welcome to part 3 of the ODX Andropause & Low T Syndrome Series. In this post, the ODX Research team reviews the best ways to approach the identification and diagnosis of Low T Syndrome and andropause.

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

Prior to diagnosing andropause/LOH, certain conditions should be ruled out including:[1] [2] [3]

• Acute illness that temporarily reduces testosterone levels
• Adjustment disorder
• Adrenal insufficiency
• Alcoholism, excess alcohol intake
• Anxiety, depression
• Bipolar disorder
• Hyperprolactinemia
• Hypothyroidism
• Growth hormone deficiency
• Lack of exercise or sleep
• Loss of energy
• Low self-esteem
• Medication use (e.g., antidepressants, antifungals, cimetidine, corticosteroids, digoxin, opioids, spironolactone)
• Midlife crisis
• Poor diet
• Smoking
• Stress
• Vitamin D deficiency

Symptoms of low T reflect a wide-range of metabolic effects including[4] [5] [6] [7] [8] [9] [10] [11] [12]

• Anemia (normochromic, normocytic)
• Bone loss
• Cantankerous mood
• Cognitive decline
• Decreased body hair
• Decreased endurance
• Decreased vitality, energy
• Depression, depressed mood
• Declining libido
• Dyspnea on exertion
• Erectile dysfunction
• Fatigue
• Frailty
• Gynecomastia, breast discomfort
• Hot flushes, sweating
• Increased body fat
• Increased sweating
• Infertility
• Irritability
• Joint pain
• Loss of height
• Lack of motivation
• Loss of body hair
• Loss of muscle strength and physical agility
• Memory issues
• Metabolic dysfunction
• Muscle weakness
• Nervousness
• Osteopenia, osteoporosis, low bone mineral density
• Hypogonadal men are twice as likely to have osteoporosis than eugonadal men[13]
• Poor concentration and memory
• Reduced physical performance
• Reduced sense of well-being, self confidence
• Sarcopenia, muscle loss
• Skin changes
• Sleep disturbances, insomnia
• Sleepiness after meals
• Slowed beard growth
• Trouble at work
• Weight gain

The presence of three or more symptoms related to sexual health (reduced libido/sexual thoughts, decreased morning erections, erectile dysfunction), should prompt further investigation into the possibility of late-onset hypogonadism. Repeated laboratory confirmation of low T in conjunction with symptoms is essential to diagnosis.[xiv]

It is important to investigate both symptoms and repeatedly low serum levels of testosterone as the occurrence of one without the other is unlikely to be genuine LOH. Remember, EMAS guidelines for LOH:[xv]

• Total testosterone below 320 ng/dL (11 nmol/L)
• Free testosterone below 64 pg/mL (220 pmol/L)

Many symptoms reported in those with LOH may be due to other metabolic dysfunctions which should be investigated. For example, symptoms of fatigue, muscle weakness, and depression may be associated with hypothyroidism, warranting further evaluation of TSH and free T4 (free T3 may be recommended as well).[xvi]

Screening questions from the Androgen Deficiency in Aging Males (ADAM) questionnaire include [xvii] [xviii]

• Do you have a decrease in libido/sex drive?
• Do you have a lack of energy?
• Do you have a decrease in strength and/or endurance?
• Have you had a loss of height?
• Have you noticed decreased enjoyment of life?
• Do you feel sad and/or grumpy?
• Are your erections less strong?
• Have you noticed a recent deterioration in your ability to play sports?
• Do you fall asleep after dinner?
• Has there been a recent deterioration in work performance?

Because erectile dysfunction may be an early warning sign of cardiovascular disease, it should be followed up with a more in-depth evaluation of cardiovascular risk.[xix] Researchers note an association of erectile dysfunction with endothelial dysfunction and other factors related to blood vessel damage such as type 2 diabetes, hypertension, and cigarette smoking.[xx]

Serial reductions in serum testosterone correlated significantly with specific disease states in a cross-sectional study of 1222 men over 40 years of age. Laboratory evidence of LOH was present in only 4.7% of symptomatic individuals without comorbidities but was found in 79% of symptomatic individuals with comorbidities.

Specific dysfunctions are associated with specific declines in T levels. In one cross-sectional study of 1222 men with LOH, significant decreases in serum TT and FT were observed with adiposity, arterial hypertension, COPD, and dyslipidemia compared to those men with LOH but none of the studies comorbidities.[xxi]

Characteristics of primary and secondary hypogonadism with organic versus functional causes.[xxii]

Optimal Takeaways for Andropause / Low T syndrome / LOH identification

• Other conditions should be ruled out before diagnosing LOH including alcoholism, mood disorders, hypothyroidism, medication use, midlife crisis, etc.
• Erectile dysfunction may be an early sign of cardiovascular disease and should be fully investigated.
• Non-sexual symptoms associated with LOH overlap with other conditions and can include decreased vitality, fatigue, irritability, lack of motivation, memory issues, muscle weakness, etc.
• Screening questionnaires help define and diagnose LOH
• The combination of symptoms and repeatedly low T is needed for diagnosis of LOH.
• Testosterone bioavailability decreases as binding globulins increase and tissue sensitivity decreases
• Primary and secondary functional hypogonadism is potentially reversible once the root causes are addressed. These include obesity, nutritional deficiencies, substance abuse, and medication use.

NEXT UP: Andropause Part 4 – Lab Assessments and Biomarker Guideposts

Research

[1] 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]

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

[3] 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]

[4] 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]

[5] Kelleher, S et al. “Blood testosterone threshold for androgen deficiency symptoms.” The Journal of clinical endocrinology and metabolism vol. 89,8 (2004): 3813-7. doi:10.1210/jc.2004-0143 [R]

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

[7] 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]

[8] 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]

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

[10] 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]

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

[12] 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]

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

[xiv] Huhtaniemi, Ilpo. “Late-onset hypogonadism: current concepts and controversies of pathogenesis, diagnosis and treatment.” Asian journal of andrology vol. 16,2 (2014): 192-202. doi:10.4103/1008-682X.122336 [R]

[xv] Huhtaniemi, Ilpo. “Late-onset hypogonadism: current concepts and controversies of pathogenesis, diagnosis and treatment.” Asian journal of andrology vol. 16,2 (2014): 192-202. doi:10.4103/1008-682X.122336 [R]

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

[xvii] 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]

[xviii] Morley, J E et al. “Validation of a screening questionnaire for androgen deficiency in aging males.” Metabolism: clinical and experimental vol. 49,9 (2000): 1239-42. doi:10.1053/meta.2000.8625 [R]

[xix] Pye, S R et al. “Late-onset hypogonadism and mortality in aging men.” The Journal of clinical endocrinology and metabolism vol. 99,4 (2014): 1357-66. doi:10.1210/jc.2013-2052 [R]

[xx] 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 [R]

[xxi] Pozarskis, A., and A. Lejnieks. "Detection of late-onset hypogonadism in men with chronic internal diseases." Proceedings of the Latvian Academy of Sciences, Section B: Natural, Exact, and Applied Sciences. Vol. 73. No. 1. 2019. .[R]

[xxii] 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]