Androgens and aging men

https://doi.org/10.1016/S0303-7207(02)00367-2Get rights and content

Abstract

This article underlines the hormonal and clinical events characterizing the so-called andropause, as they may be described from an extensive review of the literature and some data obtained with the French colleagues of the author. Evidence-based hormonal intervention has to be positioned against anti-aging entrepreneurs who peddle hormones at random. The desequilibrium in aging men between the unchanged level of plasma cortisol and the profound decrease of androgens deserves cautious studies to eventually oppose this unbalanced hormonal situation effectively and safely.

Introduction

In women's life, when they are approximately 50 years old, a remarkable event occurs still at the same age as a century ago when longevity was much shorter, ovulation stops and, therefore, fertility and consequently estradiol, the archetypal estrogen, becomes very low in the blood—lower (naturally in absence of replacement administration) than it is in men and even aging men (Table 1, Vermeulen et al., 1999). In women, hormone replacement therapy, mainly with estrogen, has obtained a recognized benefit for several estrogen deficit-associated physical impairments, the XXth century was that of the discoveries of sex hormones, of their main mechanism of action at the gene expression level via nuclear receptors, and of the synthesis of synthetic active derivatives and preparations permitting relatively easy utilization, including thanks to recent specific estrogen receptor modulators (SERMs) which may display differential activity in different receptor-positive target cells.

Where are we, men of my generation whose mean life expectancy, particularly in our ‘advanced’ countries, is several years shorter than that of women, even reaching 80 years for approximately half of us? Clearly the second part of men's life is not as hormonally standardized and selective as in women, even some decline of the testicular endocrine function is always there (Tenover et al., 1988, Vermeulen and Deslypere, 1985), the decrease of blood testosterone (Fig. 1, Seidman and Walsh, 1999) and its active metabolite 5α-dihydrotestosterone (DHT; Fig. 2) is globally incomplete but variably according to individuals, whose several other health parameters may be deficient while fertility, even certainly decreased, is, however, far to be abolished, many sperm characteristics are preserved (Nieschlag et al., 1982), but Sertoli cells are functionally diminished. What is functionally much a problem in terms of quality of life has been summarized under the heading of ‘climacteric’ symptoms (Table 2; Bauer, 1944, McKinlay et al., 1989, Werner, 1946, Heinemann et al., 1999), very similar to those of women with an emphasis on the decrease of sex life components—from diminished sexual desire to several forms of impotence. If the hormonal status of menopause, even including the pre- and perimenopausal symptoms, is rather rapidly established in a few months, there is a long period—many years—during which a ‘partial Androgen Deficiency in Aging Men’, the so-called PADAM, is slowly progressing, even the precise criteria have not yet been established. It follows that it is particularly difficult to decide if the observed physical (and mental) changes in aging men are dependent on hormonal modifications, or whether the androgen deficit is consequent of age-related alterations. Consequently, one may predict that androgen substitution is difficult to rationalize and its potential beneficial effects relatively uncertain. However, currently PADAM is increasingly recognized as important for health and quality of life issue. To give approximative values exemplifying the hormonal deficit, we may cite the mean level observed in 75 years old men as 2/3rd of that of young men, sexual dysfunction in young men being observed when testosterone is ≤3 ng/ml (≤10 nmoles). The bioavailable testosterone is lower in 25% of aged men than the lowest normal young values.

Section snippets

Hormones

The basis of any scientific reasoning is to be found in publications measuring carefully hormonal and other behavioral and physical parameters. Circulating (plasma) testosterone, practically of only testicular origin, decreases each year of approximately 0.5–1% between 40 and 70 years, and this decrease of circulating testosterone is logically associated to (and probably responsible for) modest LH increase (Morley et al., 1997a, Morley et al., 1997b), with attenuation of secretory burst

DHEA(S)

In most men as in most women, there is a profound decrease of DHEA(S) correlated with age (Orentreich et al., 1984, Fig. 5). DHEA(S) means DHEA itself, the unconjugated form in a few ng/ml concentration, and DHEAS, its ester-sulfate form, principally of adrenal secretion origin and very abundant: still in more than 60 years old men, normal values are in the μg/ml range. Both forms are decreased in aging. As indicated in Fig. 6, DHEAS has to be hydrolyzed to give DHEA which itself is metabolized

A few clinically related remarks

Aging is not a synchronous process as far as its different characteristics, it is even more evident clinically than hormonally. I only write down a few remarks.

References (45)

  • E.E. Baulieu et al.

    Dehydroepiandrosterone (DHEA), DHEA sulfate, and aging: contribution of the DHEAge study to a sociobiomedical issue

    Proc. Natl. Acad. Sci. USA

    (2000)
  • R.N. Baumgartner et al.

    Predictors of skeletal muscle mass in elderly men and women

    Mech. Ageing Dev.

    (1998)
  • H.M. Behre et al.

    Testosterone treatment and the prostate

  • W.J. Bremner et al.

    Loss of circadian rhythmicity in blood testosterone levels with aging in normal men

    J. Clin. Endocrinol. Metab.

    (1983)
  • D. Crook

    Androgen therapies and the risk of cardiovascular disease

  • D.E. Cummings et al.

    Prostate-sparing effects in primates of the potent androgen 7α-methyl-19-nortestosterone: a potential alternative to testosterone for androgen replacement and male contraception

    J. Clin. Endocrinol. Metab.

    (1998)
  • L.J.G. Gooren

    Male reproductive health: what are the issues

  • J.S. Janowsky et al.

    Testosterone influences spatial cognition in older men

    Behav. Neurosci.

    (1994)
  • K. Krithivas 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

    J. Endocrinol.

    (1999)
  • S. Kudlacek et al.

    Hormones and osteoporosis in the aging male

    The Aging Male

    (1999)
  • S. Legrain et al.

    Dehydroepiandrosterone replacement administration: pharmacokinetic and pharmacodynamic studies in healthy elderly subjects

    J. Clin. Endocrinol. Metab.

    (2000)
  • B. Lunenfeld

    Hormone replacement therapy in the aging male

    The Aging Male

    (1999)
  • Cited by (45)

    • New insights of CYP1A in endogenous metabolism: a focus on single nucleotide polymorphisms and diseases

      2020, Acta Pharmaceutica Sinica B
      Citation Excerpt :

      This fact has attracted the attention of researchers because the increased risk of prostate cancer with age does not match the decrease in free testosterone levels in older men. In particular, an increased ratio of estradiol to testosterone was detected with age148,151–154. Estrogen receptor is usually detected in the prostate and decreases when canceration occurs, but it is usually retained, and the recurrence rate of prostate cancer is relatively high149,155,156.

    • Bone and androgens

      2014, Presse Medicale
    • Effects of moderate exercise over different phases on age-related physiological dysfunction in testes of SAMP8 mice

      2013, Experimental Gerontology
      Citation Excerpt :

      Male aging is typically accompanied by reduced serum levels of testosterone, which are associated with declines in reproductive function, muscle strength, bone density and other physiological parameters (Baulieu, 2002).

    • Sex- and endocrine-stage-differences in middle-aged rats in an animal model of OCD

      2013, Progress in Neuro-Psychopharmacology and Biological Psychiatry
    • Role of DHEA in cardiovascular diseases

      2013, Biochemical Pharmacology
    View all citing articles on Scopus
    View full text