Testosterone, Aging and the Mind
When men (and, for that matter, women) think about the powers of testosterone, they are not likely to consider mental processes. Indeed, the male hormone has much more obvious roles in a man's body. Still, new research suggests that testosterone may have a surprising role in masculine mentality.

Before you consider how testosterone affects the mind -- and before you even begin to think about hormone therapy -- you should know how testosterone is produced, how it affects the body, how it changes with age, and how it's measured.

The Testosterone Connection

Although testosterone is the most potent male hormone (androgen), it is only one of many. When the ancient Greeks provided the name, they chose well: "androgen" comes from the words for "man-maker," and, indeed, androgens make the man, or at least his characteristic male traits.

Androgen production requires a complex chain of events (see figure below). It all begins in the brain, where the hypothalamus produces gonadotropin-releasing hormone (GnRH, also known as luteinizing hormone-releasing hormone, LHRH). Hormones are chemicals that are produced in one part of the body, then travel to another part where they do their work. GnRH is a true hormone, but it doesn't have a long commute; it acts on a nearby part of the brain, the pituitary gland. In turn, the pituitary secretes two additional hormones, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). FSH and LH were named for their effects on women's ovaries, but they are every bit as important for men, since they act on the testicles: LH triggers testosterone production, and FSH, acting with testosterone, stimulates sperm production.

Testosterone is produced by the Leydig cells of the testicles. The starting point is cholesterol, notorious for its effects on the heart but critical for its role as the building block of all sex hormones, both male and female. After several intermediate steps, cholesterol is converted into androstenedione, the hormone made infamous by Mark McGwire as the unregulated " dietary supplement" andro. Whether androstenedione comes from the body or a bottle, it is rapidly converted into testosterone.

Testosterone has many direct effects on the male anatomy and metabolism. It is responsible for the deep voice, increased muscle mass, and strong bones that characterize the gender. It stimulates the production of red blood cells by the bone marrow. The hormone also has crucial, if incompletely understood, effects on male behavior: It contributes to aggressiveness, and it is essential for the libido (sex drive), as well as for normal erections and sexual performance. Testosterone stimulates the growth of the genitals at puberty, and it is responsible for sperm production throughout adult life. Finally, it influences cholesterol metabolism, but scientists are still not sure how that affects health.

Although testosterone acts directly on many tissues, some of its least desirable effects don't occur until it is converted into another androgen, dihydrotestosterone (DHT). DHT acts on the skin, sometimes producing acne, and on the hair follicles, putting hair on the chest but often taking it off the scalp. Male-pattern baldness is one thing, but prostate disease quite another: DHT also stimulates the growth of prostate cells, producing normal growth in adolescents but contributing to benign prostatic hyperplasia and prostate cancer in many older men.

About 95% of a man's testosterone is produced in the testicles under the control of LH. The remaining 5% is produced in his adrenal glands. Women also make testosterone in their adrenal glands. In both sexes, adrenal hormone production does not depend on LH or FSH, and in both sexes, an important precursor of testosterone is dehydroepiandrosterone (DHEA), another hormone that is widely popular as a nonprescription "dietary supplement."

Testosterone metabolism has a final complexity. In its last throes, this quintessential male hormone is converted to estradiol, a major female hormone. Most of this final conversion takes place in fat cells, which is why obese men and women have higher estrogen levels than lean men and women.

Testosterone and the Life Cycle

In males, testosterone production begins very early indeed, usually at the start of the seventh week of embryonic development. Testosterone levels remain high throughout fetal life, but they fall just before birth, so they're only slightly higher in newborn boys than girls. Baby boys experience a blip in testosterone production between three and six months of age, but by a year their levels are back down. Between six and eight years of age, adrenal androgen production rises, triggering a transient growth spurt and a bit of body hair but no sexual development.

At puberty, a surge in GnRH and LH fire up testosterone production, and testosterone goes on to stimulate the growth of bones and muscles, the production of red blood cells, an enlargement of the voice box, the growth of facial and body hair, an enlargement of the genitals, and an awakening of sexual function and reproductive capacity. In most young men, testosterone production reaches its maximum at about age 17, and levels remain high for the next two to three decades. On average, healthy young men produce about six milligrams of testosterone a day.

In some men, testosterone levels remain high throughout life, but in most they begin to decline at about age 40. Unlike the precipitous drop in hormones that women experience at menopause, however, the decline in men is gradual, averaging just over 1% a year. This drop is imperceptible at first, but by age 70, the average man's testosterone production is 30% below its peak. Still, testosterone levels remain within the normal range in at least 75% of older men, which is why many men can father children in their 80s and beyond. And older men who worry about declining testosterone may be reassured by a study that found no link between low testosterone levels and the risk of erectile dysfunction, as well as by another that found no relationship between an older man's testosterone level and his mortality rate.

What's Normal?

It's a simple question with a complex answer. Instead of a single normal level for testosterone, normal men exhibit a wide range, with testosterone levels between 270 and 1,070 nanograms per deciliter (ng/dL). But, like so many biological functions, testosterone production waxes and wanes over a 24-hour cycle; production is highest at 8 a.m. and lowest at 9 p.m. For measurements to be meaningful, they should be obtained at a standard time, usually first thing in the morning. Timing is particularly important when testing older men; because age takes a greater toll on the morning peak production than on the afternoon plateau, a late-day level can look normal, but a feeble morning surge can still leave a man's 24-hour production low.

The aging process introduces a final complexity. Testosterone travels in the blood in one of two forms, either bound to one of two proteins or free and unbound. The hormone binds tightly to sex hormone-binding globulin but only weakly to the second protein, albumin. Only the free and albumin-bound forms of testosterone are biologically active; together, they are known as bioavailable testosterone. The sex hormone-binding protein rises with age, so an older man may have a normal total testosterone level but still be low where it counts, in bioavailable testosterone.

A man may not need to know all of the ins and outs of testosterone metabolism, but he should understand that these complexities account for important flaws in much of the research on testosterone replacement therapy. If you need to know where you stand, you should ask to have your total testosterone and free or bioavailable testosterone levels measured, preferably early in the morning. The table below shows the testosterone levels observed in one study of healthy men between 40 and 79 years of age.