“TESTOSTERONE, TO DO OR NOT TO DO, THAT IS THE QUESTION”

 

I have male patients that are either taking testosterone pharmaceuticals or question whether they should be considering this hormone as part of their daily regimen. Let us begin by discussing the basics.

Testosterone is the primary male sex hormone and anabolic steroid. It plays a key role in the development of the male reproductive organs such as the penis, scrotum, testi and prostate named androgenic effects and also promotes increased muscle mass, strength, bone density, protein synthesis called anabolic effects. Other effects such as facial hair and underarm hair are part of the secondary sex characteristics.

Testosterone is a steroid and is biosynthesized in several steps from cholesterol and is converted in the liver to inactive metabolites. In humans it is secreted by the testi of males and to a lesser extent the ovaries of females. The adrenal glands also secrete small amounts. In adult males levels of testosterone are 7-8 greater as in adult females (although there are certain abnormal conditions that cause increase testosterone levels in females.)There are many effects of testosterone in utero (before birth) but this is not part of this article

Prepubertal androgen levels rise in both boys and girls and cause body odor, increased oiliness of skin due to enlargement of sebaceous glands causing acne and other normal reactions. Puberty results in higher levels in females and this occurs later in males. This causes spermatogenesis in testi, male fertility, penis and clitoris enlargement and in conjunction with growth hormone from the anterior portion of the pituitary gland causes growth of jaw, brow, chin, nose and as well as other musculoskeletal enhancements. The biological function includes normal sperm development via sertoli cells a process known as spermatogenesis.

Blood levels of testosterone vary greatly among men, according to the Mayo Clinic. Testosterone also fluctuates throughout the course of a man’s life, usually peaking at about age 35. It begins declining at age 30, at a rate of about 1% a year. Many men don’t begin feeling the symptoms of low testosterone until about ages 45-60, even if testosterone decline started years prior, according to the National Institutes of Health.

The normal range of testosterone in men is between 270 ng/dL to 1070 ng/dL. The average testosterone level among healthy males is 679 ng/dL. In the biosynthesis of testosterone being a steroid needs cholesterol in its production. If one is reducing their overall cholesterol levels via diet or statin drugs this could hinder not only testosterone production but the development of other cholesterol dependent  hormones as well  vitamin D  which is really not a vitamin but a steroid hormone, thus it also needs cholesterol.

 

While women also naturally produce testosterone, they do so at much smaller levels, the NIH says. The normal testosterone level for women is between 15 ng/dL and 70 ng/dL, a fraction of what is normal for men.

Two questions come to mind regarding its use pharmaceutically:

1)is it safe and 2) is it effective. I have always leaned away from recommending using testosterone for a simple reason and that is there is a reason that age causes a reduction in certain chemicals in the body usually for our protection. Below is a recent study that came to light regarding testosterone.

Testosterone Therapy: Five New Reports Offer a Mixed Bag

By Amy Orciari Herman

New findings from the NIH-supported “Testosterone Trials” offer a mixed take on the potential role of testosterone therapy in older men. In the trials, men aged 65 and older with serum testosterone below 275 ng/dL plus sexual or physical dysfunction or reduced vitality were randomized to use testosterone gel (1%) or placebo for 1 year.

Among the findings, as reported in JAMA:

— Coronary artery plaque was assessed by computed tomographic angiography in 170 participants. From baseline to 12 months, testosterone treatment was associated with a greater increase in noncalcified plaque volume relative to placebo.

— Among nearly 500 participants with age-associated memory impairment at baseline, testosterone therapy did not confer improvements in memory or other cognitive measures compared with placebo.

A JAMA editorialist says that with these findings, “the hopes for testosterone-led rejuvenation for older men are dimmed and disappointed if not yet finally dashed.”

Separately, from JAMA Internal Medicine:

— Bone mineral density (BMD) and strength were assessed among roughly 200 trial participants. Testosterone therapy was associated with increases in volumetric BMD at the spine and hip, plus increases in bone strength, compared with placebo.

— Among nearly 130 participants with anemia, hemoglobin levels increased (by at least 1 g/dL) more often with testosterone than with placebo.

— Separate from the “Testosterone Trials”, researchers retrospectively studied over 44,000 men with androgen deficiency. Over roughly 3 years, the cardiovascular event rate was lower in men prescribed any testosterone than in untreated men (17 vs. 24 per 1000 person-years).

 

A JAMA Internal Medicine editorialist says the health benefits of the increased BMD and hemoglobin levels are unclear, and “the cardiovascular risks and benefits of testosterone replacement … have not been adequately resolved.”

 

William E. Chavey, MD, MS: This story will not ameliorate all of the controversy surrounding testosterone therapy. Nevertheless, it provides at least a little signal among all of the noise that might provide some guidance to primary care physicians.