BERKELEY, CA (UroToday.com) - In their review paper, Saad and Gooren elegantly contrast the differences between late onset hypogonadism and menopause. Many men who reach middle-age start to experience symptoms that resemble those of menopause; reduced libido, lack of energy, weight gain, fatigue, and depression, to name a few. Therefore these conditions are frequently seen as being equivalent, and late onset hypogonadism has therefore been called "andropause," "male climacteric" and "male menopause." However, as Saad and Gooren correctly point out, this is very misleading.
For several reasons, late onset hypogonadism and menopause cannot be equated: menopause is universal and obvious and manifests relatively rapidly, the consequences of treatment, the hormones involved are different, and treatment vs. non-treatment has vastly different consequences.
Hypogonadism, also known as testosterone deficiency, while common, does not universally affect every man. It has been shown that testosterone levels display no decrease associated with age among men over 40 years of age who self-report very good or excellent health. This may indicate that a large part of the age-related decline in testosterone levels is due to accumulating age-related co-morbidities, rather than an age-specific phenomenon. This view is supported by data showing that besides age per se, obesity, metabolic syndrome, diabetes, and dyslipidemia are risk factors of incident hypogonadism. Thus, while menopause happens consistently in women between the ages of 45-55, the median age for natural final menstrual period is 52 years, hypogonadism in men can occur at any age because testosterone deficiency can be caused by several different factors.[6, 7] Therefore, the term "late onset hypogonadism" is inappropriate. The terms testosterone deficiency and hypogonadism are more accurate.
Male testosterone deficiency develops slower and more progressively over time, while menopause signifies a relatively abrupt cessation of estradiol production. In both cross-sectional[8, 9, 10, 11, 12, 13] and longitudinal studies,[14, 15, 16, 17] beginning in the third decade in men, testosterone levels start to decline gradually and progressively at a rate of approximately 1% per year.
Equating late onset hypogonadism and menopause also disguises the facts that these phenomena are caused by different hormones, and that their respective deficiencies result in difference consequences. While estrogen deficiency in women seems to be protective against cancer[18, 19] and may increase longevity, testosterone deficiency in men is associated with a myriad of detrimental health outcomes, including obesity, increased waist circumference, insulin resistance, type 2 diabetes, hypertension, inflammation, atherosclerosis and cardiovascular disease, erectile dysfunction (ED), and increased mortality. Testosterone deficiency in men may even be a risk factor for cardiovascular disease. In addition, there are also indications that testosterone deficiency in men contributes to the gender gap in cardiovascular morbidity and mortality.
When it comes to the issue of treatment vs non-treatment, a growing body of evidence justifies treatment of hypogonadism with testosterone therapy. This is in stark contrast to menopause, whose treatment with estrogen replacement therapy (HRT) is controversial; studies show it doesn't always improve symptoms and it may have negative health effects.[24, 25, 26, 27, 28] The most serious concern about traditional estrogen HRT (hormone replacement therapy) is its potential to increase risk for breast and endometrial cancer, blood clots, stroke and heart disease. In contrast, treatment of hypogonadism in men reduces risk of multiple chronic diseases, including cardiovascular disease.[30, 31]
An important reason to distinguish hypogonadism from menopause is because concerns about HRT in postmenopausal women have been inappropriately extrapolated to men; "such extrapolation is not only inappropriate but it lacks any scientific evidence or validity...” Predicting the effects of testosterone replacement in hypogonadal men by relying on studies of estrogen (with or without progesterone) in postmenopausal women is baseless and should be condemned.
The conclusion by Saad and Gooren that testosterone treatment in hypogonadal men is more compelling than estrogen treatment of postmenopausal women is well backed up by solid scientific research and provides a timely message to practicing clinicians who still think that "andropause" or "male climacteric" should be approached like menopause.
- Saad F, Gooren LJ. Late onset hypogonadism of men is not equivalent to the menopause. Maturitas. 2014.
- Zarotsky V, al e. Systematic Literature Review of the Epidemiology of Nongenetic Forms of Hypogonadism in Adult Males. Journal of Hormones. 2014;Volume 2014, Article ID 190347.
- Sartorius G, Spasevska S, Idan A, et al. Serum testosterone, dihydrotestosterone and estradiol concentrations in older men self-reporting very good health: the healthy man study. Clinical Endocrinology. 2012;77(5):755-763.
- Haring R, Ittermann T, Volzke H, et al. Prevalence, incidence and risk factors of testosterone deficiency in a population-based cohort of men: results from the study of health in Pomerania. The Aging Male: the official journal of the International Society for the Study of the Aging Male. 2010;13(4):247-257.
- Gold EB, Crawford SL, Avis NE, et al. Factors related to age at natural menopause: longitudinal analyses from SWAN. American Journal of Epidemiology. 2013;178(1):70-83.
- Kelleher S, Conway AJ, Handelsman DJ. Blood testosterone threshold for androgen deficiency symptoms. The Journal of Clinical Endocrinology and Metabolism. 2004;89(8):3813-3817.
- Tajar A, Forti G, O'Neill TW, et al. Characteristics of secondary, primary, and compensated hypogonadism in aging men: evidence from the European Male Ageing Study. The Journal of Clinical Endocrinology and Metabolism. 2010;95(4):1810-1818.
- Vermeulen A. Clinical review 24: Androgens in the aging male. The Journal of clinical endocrinology and metabolism. 1991;73(2):221-224.
- Zumoff B, Strain GW, Kream J, et al. Age variation of the 24-hour mean plasma concentrations of androgens, estrogens, and gonadotropins in normal adult men. The Journal of Clinical Endocrinology and Metabolism. 1982;54(3):534-538.
- Ferrini RL, Barrett-Connor E. Sex hormones and age: a cross-sectional study of testosterone and estradiol and their bioavailable fractions in community-dwelling men. American Journal of Epidemiology. 1998;147(8):750-754.
- Gray A, Feldman HA, McKinlay JB, et al. Age, disease, and changing sex hormone levels in middle-aged men: results of the Massachusetts Male Aging Study. The Journal of Clinical Endocrinology and Metabolism. 1991;73(5):1016-1025.
- Leifke E, Gorenoi V, Wichers C, et al. Age-related changes of serum sex hormones, insulin-like growth factor-1 and sex-hormone binding globulin levels in men: cross-sectional data from a healthy male cohort. Clinical Endocrinology. 2000;53(6):689-695.
- Simon D, Preziosi P, Barrett-Connor E, et al. The influence of aging on plasma sex hormones in men: the Telecom Study. American journal of epidemiology. 1992;135(7):783-791.
- Harman SM, Metter EJ, Tobin JD, et al. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. The Journal of Clinical Endocrinology and Metabolism. 2001;86(2):724-731.
- Krithivas K, Yurgalevitch SM, Mohr BA, et al. Evidence that the CAG repeat in the androgen receptor gene is associated with the age-related decline in serum androgen levels in men. The Journal of Endocrinology. 1999;162(1):137-142.
- Morley JE, Kaiser FE, Perry HM, 3rd, et al. Longitudinal changes in testosterone, luteinizing hormone, and follicle-stimulating hormone in healthy older men. Metabolism: Clinical and Experimental. 1997;46(4):410-413.
- Zmuda JM, Cauley JA, Kriska A, et al. Longitudinal relation between endogenous testosterone and cardiovascular disease risk factors in middle-aged men. A 13-year follow-up of former Multiple Risk Factor Intervention Trial participants. American Journal of Epidemiology. 1997;146(8):609-617.
- Neilson HK, Conroy SM, Friedenreich CM. The Influence of Energetic Factors on Biomarkers of Postmenopausal Breast Cancer Risk. Current Nutrition Reports. 2014;3:22-34.
- Travis RC, Key TJ. Oestrogen exposure and breast cancer risk. Breast Cancer Research: BCR. 2003;5(5):239-247.
- Maggio M, Ceda GP, Lauretani F, et al. Relationship between higher estradiol levels and 9-year mortality in older women: the Invecchiare in Chianti study. Journal of the American Geriatrics Society. 2009;57(10):1810-1815.
- Traish AM. Adverse health effects of testosterone deficiency (TD) in men. Steroids. 2014.
- Jones TH. Testosterone deficiency: a risk factor for cardiovascular disease? Trends in Endocrinology and Metabolism: TEM. 2010;21(8):496-503.
- Haring R, John U, Volzke H, et al. Low testosterone concentrations in men contribute to the gender gap in cardiovascular morbidity and mortality. Gender Medicine. 2012;9(6):557-568.
- Thomson J, Oswald I. Effect of oestrogen on the sleep, mood, and anxiety of menopausal women. British Medical Journal. 1977;2(6098):1317-1319.
- George GC, Utian WH, Beaumont PJ, et al. Effect of exogenous oestrogens on minor psychiatric symptoms in postmenopausal women. South African Medical Journal = Suid-Afrikaanse tydskrif vir geneeskunde. 1973;47(49):2387-2388.
- Barnabei VM, Cochrane BB, Aragaki AK, et al. Menopausal symptoms and treatment-related effects of estrogen and progestin in the Women's Health Initiative. Obstetrics and Gynecology. 2005;105(5 Pt 1):1063-1073.
- Ortmann O, Lattrich C. The treatment of climacteric symptoms. Deutsches Arzteblatt international. 2012;109(17):316-323; quiz 324.
- Marjoribanks J, Farquhar C, Roberts H, et al. Long term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev. 2012;7:CD004143.
- de Villiers TJ, Pines A, Panay N, et al. Updated 2013 International Menopause Society recommendations on menopausal hormone therapy and preventive strategies for midlife health. Climacteric: Journal of the International Menopause Society. 2013;16(3):316-337.
- Traish AM. Outcomes of testosterone therapy in men with testosterone deficiency (TD): Part II. Steroids. 2014.
- Oskui MP, French WJ, Herring MJ, et al. Testosterone and the cardiovascular system: a comprehensive review of the clinical literature. Journal of the American Heart Association. 2013;2(6):e000272.
- Morales A. The andropause: bare facts for urologists. BJU international. 2003;91(4):311-313.
Monica Caliber, MSc as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
MSc in Nutrition
University of Stockholm/Karolinska Institute, Sweden
Baylor University, TX USA