Late onset hypogonadism of men is not equivalent to menopause

December 2014

Saad F, Gooren LJ. Maturitas. 2014 Sep;79(1):52−7.

In their review paper, Saad and Gooren elegantly contrast the differences between late onset hypogonadism, also known as testosterone deficiency, 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, depression and osteoporosis, to name a few.2-6

Therefore these conditions are frequently seen as being equivalent, and late onset hypogonadism has therefore been called "andropause", "male climacteric", "male menopause" or "MANopause. However, as Saad and Gooren correctly point out, this is very misleading.

KEY POINTS

  • Menopause is universal and obvious and develops relatively rapidly.
    1. Hypogonadism does not affect every man, and when it does, it develops slowly over a long time period.
  • The hormones involved are different.
    1. Estrogen and testosterone have contrasting effects on most physiological functions.
  • Treatment vs. non-treatment has vastly different consequences.
    1. Reduced levels of testosterone in men contribute to the development of cardiovascular disease, and may, despite long-held beliefs to the opposite, have a negative impact on the prostate. It is also well documented that hypogonadism increases mortality and that testosterone therapy may reduce mortality and may even increase longevity.
    2. The consequences of reduced levels of estrogen in postmenopausal women are less well-documented, and treatment with estrogen (hormone replacement therapy, HRT) likely confers a different risk-benefit ratio than treatment of hypogonadism with testosterone therapy.

What is known

Testosterone deficiency often manifests with symptoms in men that resemble those of menopausal women.2,6,10,11 This has given rise to the idea of "andropause", "male climacteric" and "male menopause". However, for several reasons, this parallel is fraught with misinformation and irrational logic that lacks a scientific base.

What this study adds

Hypogonadism, also known as testosterone deficiency, while common12, 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.13 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.14 Thus, while menopause happens consistently in women between the ages of 45-55, the median age for natural final menstrual period is 52 years15, hypogonadism in men can occur at any age because testosterone deficiency can be caused by several different factors.11,16 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-sectional17-22 and longitudinal studies23-26, beginning in the third decade in men, testosterone levels start to decline gradually and progressive 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 vastly different consequences. While it is hypothesized that estrogen deficiency in women may be protective against cancer27,28 and may increase longevity29, 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.30 Testosterone deficiency in men may even be a risk factor for cardiovascular disease.31,32 In addition, there are also indications that testosterone deficiency in men contributes to the gender gap in cardiovascular morbidity and mortality.33 When it comes to the prostate, testosterone deficiency may actually - to the contrary of old dogma - have a negative impact on prostate health, as we have reported in a previous editorial “Testosterone and prostate cancer - a paradigm shift”.

When it comes to the issue of treatment vs. non-treatment, a rapidly expanding body of evidence justifies treatment of hypogonadism with testosterone therapy.34-53 This is in stark contrast to menopause, whose treatment with estrogen replacement therapy (HRT) is controversial54-58 The most serious concern about traditional estrogen HRT is its potential to increase risk for breast and endometrial cancer, blood clots, stroke and heart disease.59 While HRT has benefited many women, the guidelines underscore that HRT must be individualized and tailored according to symptoms and the need for prevention, as well as personal and family history of morbidity.59 In contrast, treatment of hypogonadism in men with testosterone therapy that achieves adequate testosterone levels and is of long enough duration to allow benefits to manifest60 improves symptoms and reduces risk of multiple chronic diseases, including cardiovascular disease, in the vast majority of men.35,37,40-43,46,47,49-52,61-67

An important reason to distinguish hypogonadism from menopause is because of 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."68

The conclusion by Saad and Gooren that testosterone treatment in hypogonadal men is far 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.

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