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Life Extension Magazine

LE Magazine October 2003
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Male Menopause
Avoiding andropause with testosterone treatment
By Edward D. Rosick

Menopause, the time in a woman’s life of distinct hormonal changes, can be very stressful both on an emotional and physical level. While men feel empathy for their loved ones who are going through this trying period, most men are also inwardly happy they don’t have to go through the mood swings, hot flashes, body aches and other effects of declining estrogen and progesterone levels that women face as they enter the fifth and sixth decades of life.[1] However, just because a man in mid-life does not feel the dramatic changes a woman undergoes doesn’t mean that he does not experience hormonal changes.

Andropause–the male menopause
As men reach their 40s, most will start noticing physical and emotional changes. Abdominal fat often takes the place of formally hard muscle, even with regular physical exercise. Eight hours of uninterrupted sleep are less frequent as nocturnal visits to the bathroom to urinate increase in frequency. The thick head of hair that once covered the head becomes gray and thinner. Every-other-night sex may turn into every-other-week sex as both interest and ability to perform decrease. And for men who are in touch with their inner feelings, they may notice that their zest for life has faded away with their libido and hairline.

Many physicians state that these changes in men are an inevitable part of “normal” aging. The idea that there is such a thing as andropause is still thought of as a myth by most mainstream medical doctors. They state that since men don’t have a physical signpost (such as the cessation of menstruation seen in women), andropause does not exist. However, even though women have a clear-cut physical demarcation in their lives, other changes of menopause take place over several years. In the case of andropause, it is thought that the majority of physical, mental and emotional changes take place over 10-to-15 years. These changes, which include declines in libido, sexual function, muscle mass and strength, increase in prostate size leading to benign prostatic hypertrophy, along with fatigue and depression, begin around age 40 for most men. It has been estimated by some researchers that today, as many as 25 million American men between 40 and 55 are experiencing signs and symptoms of andropause.

Testosterone–the key to andropause
In women, estrogen and progesterone are the two key hormones that decline during menopause. In men, it is the hormone testosterone that falls most in production as a man ages, and it’s thought that this fall is the single most important cause of andropause. Testosterone levels peak in a man at approximately age 30 and then begin a gradual decline.[2] Some men have low testosterone by age 40. One reason that aging men are not diagnosed as being testosterone deficient is that blood test laboratory reference ranges are age-adjusted to reflect the anticipated reduction in testosterone production. So, when a doctor looks at an aging man’s free testosterone blood test result, he often sees it fitting neatly into the standard reference range for a normal aging man. The problem is that normal aging men are expected to have lower testosterone levels, which are far from optimal (youthful) ranges. The optimal testosterone level for most aging males are those of a healthy 21-to-30 year old. Testosterone is vitally important for its anabolic properties, including effects on cholesterol levels, protein breakdown, muscle mass and bone density, and its androgenic effects, including the development and maintenance of male secondary sex characteristics (deep voice, increase in facial and body hair, muscle development) and sexual functions such as libido and erection capability.

Testosterone begins in the brain
While early scientists focused on the testicles as the source of testosterone, medical researchers of today know that the first step in the production of testosterone starts in the brain. This biochemical cascade begins in the part of the brain known as the hypothalamus, which secretes gonadotropin-releasing hormone (GnRH). This hormone then signals the pituitary gland, to make follicle-stimulating hormone (FSH) and lutenizing hormone (LH). Normal levels of FSH prompt the testicles to produce sperm, while LH stimulates the production of testosterone via the Leydig cells in the testicles. While it’s been estimated that a man begins life with 700 million Leydig cells, he begins to lose six million of those cells yearly after his twentieth birthday.[3]

After testosterone is secreted into the bloodstream via the Leydig cells, its fate can follow a few different pathways. Some testosterone attaches to sex hormone binding globulin, or SHBG. Testosterone not bound up with SHBG is known as free testosterone, and it is in this form that it can exert its powerful anabolic and androgenic effects on the human body. Testosterone can also be converted via enzymatic pathways into different hormones. Through the actions of 5-alpha-reductase, an enzyme found in multiple tissues but especially high in the prostate gland, testosterone can be converted into dihydrotestosterone (DHT). Aromatase, an enzyme in skin, fat, bone and brain cells, actually changes testosterone into estrogen. Estrogen (which actually is not just one hormone but several related compounds) has been recently discovered to be important in many physiological functions in men, including maintenance of bone mass and cognitive function.[1]

While some estrogen is essential for health in men, too much of it can be bad, especially when it’s in the form of 16-alpha-hydroxyestrone, a breakdown product of estrogen metabolism that has been implicated in cancer. Another estrogen metabolite, 2-hydroxyesterone, is believed to be much less harmful, and in fact, a ratio tilting toward 2-hydroxyesterone is thought to be beneficial.

How testosterone changes in aging men
One change found in aging is in the ratio of free testosterone to testosterone bound to SHBG. In many aging men, especially those who are obese, free testosterone levels drop significantly as the levels of SHBG increase and “bind up” whatever free testosterone is left. As if this news isn’t bad enough, there are also steep declines (40% to 75%) in other steroid hormones, including dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEA-S) seen in men as they age from 20 to 80.[4]

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