Low Testosterone

Content written by Irwin Goldstein, MD

It has been incorrectly assumed that estrogen is a hormone for women and testosterone is a hormone for men. Even though, historically, testosterone has been related to men and to male physical attributes and behaviors, it has been shown almost 70 years ago that women’s bodies also synthesize testosterone and the testosterone in women is chemically identical with the testosterone in men. In women, it is now appreciated that approximately 25% of testosterone synthesis occurs in the ovaries, 25% in the adrenal glands and 50% in the rest of the body. In women, testosterone acts on testosterone (androgen) receptors to direct the synthesis of numerous critical proteins that are involved in the structure and function of many tissues. In women, it has been shown that testosterone receptors exist in brain, bone, breast, skin, sweat glands, skeletal muscle, fat and genital tissues. In women, testosterone has been shown to affect sexual desire, bone density, muscle mass and strength, fat tissue distribution, mood, energy, and psychological well-being.

Although controversy exists concerning use of testosterone therapy in women, testosterone therapy has been used for women for almost 70 years for suspected testosterone deficiency states. When a woman has low estrogen values, such as in menopause, predictable symptoms develop such as hot ?ashes, nights sweats, poor memory, depression, dry skin, weight gain, and vaginal dryness. It is a little less clear what the symptoms are when a woman has low testosterone values. The term female testosterone insufficiency has been defined as consisting of a pattern of clinical symptoms in the presence of decreased testosterone and normal estrogen status. Symptoms of testosterone insuf?ciency most often reported include: a diminished sense of well-being or unpleasant mood; persistent, unexplained fatigue; and sexual function changes, including decreased libido, sexual receptivity, and pleasure. Other potential symptoms of testosterone insufficiency include bone loss and decreased muscle strength. The diagnosis of testosterone insuf?ciency is made in women who have normal levels of estrogen such as normally cycling premenopausal women or post-menopausal women receiving estrogen replacement therapy.

Testosterone insufficiency can occur due to problems of the ovary, adrenal gland, and of the hypothalamus-pituitary (regions of the brain). Testosterone insufficiency can also occur secondary to drug use, such as steroids, anti-testosterone drugs, oral contraceptives, and oral estrogen replacement therapies. Testosterone insufficiency can also occur for unknown reasons. Testosterone levels fall regularly across a woman’s life. For example, testosterone levels in a 40-year-old woman are about half of what they are in 20-year-old woman.

Before starting testosterone replacement therapy, a clinical assessment should be performed by a physician. This evaluation should include a medical and psychosocial history, physical examination, and laboratory testing. This is relevant since testosterone insufficiency may be mimicked by other conditions such as a major life stress or relationship con?icts, thyroid disease, major metabolic or nutritional disorders, other causes of chronic fatigue and psychiatric disorders. The diagnosis of testosterone insufficiency syndrome includes the presence of clinical symptoms, normal estrogen blood test values and a low blood test value for testosterone. A low testosterone value has been consensed to be at or below the lowest fourth of the normal range for the reproductive age (20 – 40 years).

In multiple randomized, double-blinded, placebo-controlled trials of surgically menopausal women with low sexual interest (hypoactive sexual desire disorder, HSDD) who were also taking estrogen treatment, the use of topical testosterone led to statistically significant and clinically meaningful improvements in sexual interest, sexual function and sexual activity, and decrease in personal distress. Similar data were found using testosterone therapy in naturally menopausal women with low sexual interest (hypoactive sexual desire disorder, HSDD).

Currently there are no approved testosterone treatments for women with hypoactive sexual desire disorder in the United States. It has been estimated that over 2 million off label prescriptions have been written in 2006-7 for women with testosterone insufficiency syndrome. Off-label therapy can include treatment with testosterone intramuscular injections, subcutaneous testosterone pellets, and topical testosterone therapy with gels. The usual starting dose for women is 10% of the dose used in men with testosterone insufficiency syndrome. As in men, testosterone blood tests should be performed in women at various intervals after treatment to improve efficacy results and decrease safety exposure

In summary, testosterone is a natural and vital sex steroid hormone in women. Testosterone, like estrogen and progesterone, has important physiologic and biologic actions in multiple tissues in a woman’s body. Testosterone values can be low for multiple reasons and a low level of testosterone can lead to pathophysiologic consequences such as sexual dysfunction, mood changes and fatigue. Testosterone replacement therapy is associated with robust clinical benefits in multiple, double blind, placebo-controlled, multi-institutional and multi-national studies. Testosterone replacement therapy in women with testosterone insufficiency syndrome remains controversial; long-term safety concerning side effects such as heart disease, heart attacks, strokes and breast cancer are still being studied. Knowledge concerning use of testosterone in women is increasing, especially since the transdermal testosterone patch has been approved by the European Union in summer 2007 and more data are being accumulated on safety data. In addition, large long-term safety data are being studied with a new investigative 1% testosterone gel in the United States.