Hormone replacement therapy (HRT) has been used in the past to treat patients who have lost the ability to make the hormones or who have reduced hormone levels. Androgen therapy in the human male has been used to treat sexual impotence and infertility, to induce sexual maturation at time of expected puberty and to maintain secondary sexual characteristics. Testosterone and its esters, e.g. testosterone enanthate and caproate, that are commonly used to treat androgen deficiency are not particularly potent androgens. Testosterone is considered to be the primary male androgen. It is responsible for the development and maintenance of male sexual characteristics, including external virilization, sexual maturity at puberty, spermatogenesis, sexual behavior/libido and erectile functioning. Testosterone also supports bone and muscle tissue growth, and remains vital to ones health and well being throughout life.
Testosterone is the main androgenic hormone formed in the testes. Testosterone therapy is currently indicated for the treatment of male hypogonadism. Hypogonadism is recognized as a common occurrence in older males. Hypogonadism may result in some of the observed decrements in muscle and skeletal mass associated with advancing age. Recent studies have suggested that androgen therapy produces a small but significant improvement in muscle strength in eugonadal males. In the hypothalamus, conversion of testosterone to estrogen results in negative feedback on gonadotropin releasing hormone and subsequent gonadotropin release. Estrogens thus normally reduce circulating testosterone and anti-estrogens result in corresponding increases. As men age, the proportion of fat to lean tissue gradually increases. Aromatization of testosterone in fat may lead to gradually increased estrogen to testosterone ratios and negative feedback that reduces total testosterone levels. Testosterone deficiency has been associated with hip fracture, and bone mass has been correlated with testosterone levels in older persons. The presence of a normal amount of libido, defined as the urge to engage in sexual activity, is an important component of an individual's well-being. In both men and women the primary naturally occurring hormone responsible for libido is testosterone. It is recognized that testosterone in females decreases with age. It is also known that sexual motivation in post menopausal women is associated with the levels of exogenously introduced testosterone. Further, providing intravenous testosterone to women as part of clinical studies is known. The presence of a normal amount of libido, defined as the urge to engage in sexual activity, is an important component of an individual's well-being. In both men and women the primary naturally occurring hormone responsible for libido is testosterone. In males, the baseline testosterone level is a relatively constant throughout life, decreasing slowly in old age. In contrast, women elaborate testosterone only as part of the process of ovulation. Each maturing follicle produces testosterone at the mid-point of the menstrual cycle, consistent with observations that female libido peaks with ovulation. As a woman ages, the number of maturing follicles per month decreases, and there is a decreasing total amount of testosterone produced. Low levels of testosterone in, e.g., hypogonadal men are associated with lack of libido and absence of erections. They respond to therapy with exogenous testosterone, and women also respond to testosterone therapy.
Testosterone replacement therapy has been used to treat patients with abnormally low testosterone levels. Testosterone replacement may be carried out by oral, intramuscular or transdermal application. When administered orally, testosterone is readily absorbed but is rapidly degraded by the liver so that only insignificant amounts reach the systemic circulation. When administered intramuscularly, testosterone is promptly absorbed from the injection vehicle, metabolized and excreted, making it difficult to achieve sustained, effective plasma levels. Males who received testosterone had a significant increase in bioavailable testosterone concentration, hematocrit, right hand muscle strength and osteocalcin concentration. Oral administration of many androgens may not be considered a safe or desirable means of replacement because of first-pass hepatic effects, hepatotoxic side effects, and the rare condition of peliosis. The replacement of the once pulsatile endogenous delivery of testosterone with the sustained blood level of the hormone produces unwanted side effects. Women taking testosterone for a few weeks typically begin to complain of the emergence of secondary sexual characteristics such as unwanted body hair, oily hair, and, with prolonged a use, deepening voice. Injectable testosterone formulations, including testosterone esters, have issues with pain and self administration, and further may produce toxic liver side effects and significantly fluctuating, hormone levels. Testosterone esters in oil depot form have been used as injections for decades, however these injections can be inconvenient and often painful. These depot injections also result in inconsistent blood levels as a supraphysiological surge is seen soon after injection but by the time the next injection is due, the levels have often dropped down below standard physiological levels. Certain undesirable physiological manifestations, such as acne vulgaris, seborrhea, female hirsutism, male pattern baldness (alopecia) and benign prostatic hyperplasia, are the result of hyperandrogenic stimulation caused by an excessive accumulation of testosterone or similar androgenic hormones in the metabolic system. |
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