Meyler's Side Effects of Endocrine and Metabolic Drugs

Jeffrey K. Aronson

• Publisher: Elsevier Science
• Year: 2009
• eBook ISBN: 9780080932927
• Topic: Medicine
• Subtopic: Pharmacology

Elsevier now offers a series of derivative works based on the acclaimed Meylers Side Effect of Drugs, 15th Edition. These individual volumes are grouped by specialty to benefit the practicing physician or health care clinician. Endocrine and metabolic diseases are common, includes diseases such as diabetes, thyroid disease, and obesity. Endocrinologists, including diabetes professionals, internal medicine and primary care practitioners, obstetricians and gynecologists, and others will find this book useful when treating endocrine or metabolic diseases.The material is drawn from the 15th edition of the internationally renowned encyclopedia, Meyler's Side Effects of Drugs, and the latest volumes in the companion series, Side Effects of Drugs Annuals. Drug names have usually been designated by their recommended or proposed International Non-proprietary Names (rINN or pINN); when those are not available, clinical names have been used. In some cases, brand names have been used.This volume is critical for any health professional involved in the administration of endocrine and metabolics mediations. - - Surpasses the Physician's Desk Reference © by including clinical case studies and independent expert analysis - Complete index of drug names - Most complete cross referencing of drug-drug interactions available - Extensive references to primary and secondary literature - Also includes information on adverse effects in pregnancy The book is divided into eight sections: - Corticosteroids and related drugs - Prostaglandins - Sex hormones and related drugs - Iodine and drugs that affect thyroid function - Insulin and other hypoglycemic drugs - Other hormones and related drugs - Lipid-regulated drugs - Endocrine and metabolic adverse effects of non-hormonal and non-metabolic drugs

SEX HORMONES AND RELATED DRUGS

Androgens and anabolic steroids

See also individual agents and Hormonal contraceptives—male

General Information

The classic androgen is natural testosterone, which can be given orally in micronized form, but has much more often been used as the orally active 17-methyl derivative or an injectable ester. Androgens are used to some extent in male hypogonadism, when they can promote libido and potency and increase the frequency of erections and the volume of the ejaculate (1). The use of androgens by either sex as “sexual tonics” is a matter of dispute. Some centers have used androgens to treat postmenopausal women complaining of weak libido, poor energy, or a feeling of malaise (2); workers who use this contentious approach have suggested that they should be given in association with estrogens, because of the adverse effects of androgens on serum lipids.

While some anabolic steroids are still available in the legitimate trade, others are manufactured and distributed illegally, and the contents and potency of these are unknown; some adverse effects could be due to impurities or content variation.

From about 1955 onwards, a number of so-called anabolic steroids were developed for which it was claimed, on the basis of animal experiments, that the virilizing effects had been reduced compared with testosterone, whereas the effects on tissue build-up and nitrogen retention had been maintained. These compounds were therefore promoted for such purposes as the promotion of appetite and weight increase in children and the advancement of convalescence. In fact, it has never been at all clear that these compounds are anything other than weak and expensive androgens. Their supposed dissociation of anabolic and androgenic effects was based on a misleading animal model and was largely disproved. The benefits that they were thought to confer in conditions such as aplastic anemia and uremia were minimal or dubious, and their adverse effects were pronounced. There are still those who would argue for the use of anabolic steroids, alongside erythropoietin, in renal anemia (3), but this practice is now unusual. Yet as they disappeared from pharmacy shelves, the anabolic steroids began to return anew through largely surreptitious channels. The western literature on the use and effects of performance-enhancing drugs as a whole suggests that anabolic-androgenic steroids are currently used in up to 1% of women, 0.53% of high school girls, 15% of men, 112% of high school boys, and up to 67% of some groups of elite athletes, often alongside other agents reputed to enhance physical development or performance (4). Even in “tonic” doses, androgens can cause virilization in women and precocious development of secondary characteristics in children. In the much higher doses later developed for use in such conditions as aplastic anemia, mammary carcinoma, terminal uremia, and even hereditary angioedema (5), their androgenic effects are very pronounced indeed, and other serious complications can occur, for example in the liver (SED-12, 1038) (6–12). One formerly well-known “anabolic” steroid, metandienone (Dianabol), was withdrawn as early as 1982, and other withdrawals have followed.

When androgen therapy is used in postmenopausal women who complain of poor libido, poor energy, or a feeling of malaise (2), it should be given in association with estrogens, because of its adverse effects on serum lipids.

Anabolic steroids are also still used in refractory anemias, although with recombinant human erythropoietin now widely available they appear to be seen mainly as a means of increasing the response to erythropoietin in highly resistant cases; combination treatment with erythropoietin, a glucocorticoid, and nandrolone has also been recommended for treating myelodysplastic syndromes (13). Again, in such exceptional situations the risks of anabolic steroids have to be accepted.

Placebo-controlled studies

A well-founded indication for the cautious use of androgens in women is to treat those who have much reduced sexual desire after a surgical menopause and are troubled by it. In a 24-week, randomized, double-blind, placebo-controlled, parallel-group, study, 447 women aged 24–70 years were randomized to receive placebo or transdermal testosterone patches in dosages of 150, 300, or 450 micrograms twice weekly, and 318 subjects completed the study (14). There were marginally significant successes in restoring sexual desire and activity, but only in the two higher dose groups. There were no serious safety concerns, but adverse effects were not discussed in detail.

Androgen replacement therapy in men

The notion that many men in later life require androgen supplementation to counter the effects of the “andropause” is more widespread in some countries than others, both among practitioners and the public, and it is heavily debated (15,16). Much of the evidence adduced to support the use of so-called “androgen supplementation” in older men, such as an attempt to demonstrate its use as a supportive treatment in depression (17), is far from convincing. Proponents of this therapy call for the development of more specific formulations for this purpose, while others argue that such treatment is rarely justified and should be strictly limited to a minority of men with severe and evident hypogonadism. It has, after all, to quote a sober review, “never been definitively established that the decline in testosterone seen in most aging men results in an androgen deficient state with health-related outcomes that can be improved by androgen therapy” (18). In that situation it is indefensible to run risks. A thorough review of the literature has turned up much evidence for the benefit of short-term testosterone treatment in selected subjects, provided prostate cancer can be excluded, but also marked reservations regarding the safety or otherwise of long-term use. Potential risks include erythrocytosis, edema, gynecomastia, and prostate stimulation. The possibility of significantly increased risks of prostate cancer and cardiovascular disease has been considered (19). Another thorough review has concluded that there is no place for such treatment in healthy older men (20). It is not clear to what extent the less favorable aspects of ageing are really attributable to androgen decline; nor is it clear that aged tissues remain androgen sensitive, nor that such treatment is necessarily safe. However, certain idiosyncratic adverse effects of androgen treatment, which can include disordered sleep and breathing, as well as polycythemia, are clearly dose related, suggesting that dose escalation to increase efficacy may create or aggravate undesirable adverse effects.

Hormonal contraception in men

The use of intramuscular testosterone + oral desogestrel for hormonal contraception in men is discussed in a separate monograph (Hormonal contraceptives—male).

General adverse reactions

Adverse effects of pharmacological doses of androgens include, as one would expect from male hormones, hirsutism with acne and other signs of virilization, along with adverse lipoprotein profiles, endometrial hyperplasia in women, and an increased risk of cardiovascular disease. Some compounds are particularly likely to cause liver disorders.

Male hormone replacement therapy has been reviewed (21). Hypogonadism can be accompanied by hot flushes, similar to those seen in postmenopausal women, and gynecomastia. The potential risks of testosterone replacement in adult men are precipitation or worsening of sleep apnea, hastened onset of clinical significant prostate disease, benign prostatic hyperplasia, prostatic carcinoma, gynecomastia, fluid retention, polycythemia, exacerbation of hypertension, edema, and an increased risk of cardiovascular disease.

The adverse effects of long-term testosterone therapy in HIV-positive men are irritability, weight gain, fatigue, hair loss, reduced volume of ejaculate, testicular atrophy, truncal acne, breast tenderness, and increased aggression (22).

Supraphysiological concentrations of androgen hormones can cause acne, hirsutism, and deepening of the voice.

Adverse effects of androgens in men

The safety of androgen therapy for cardiovascular and prostatic disease is uncertain. Kraus, after a careful review of the literature from a German perspective, has pointed out that androgen substitution must be approached with caution; even if the hazards are dubious, the need for such treatment is even more doubtful: “…. The lack of clear hazards from testosterone substitution in the aging male does not indicate unrestricted treatment safety. Until all doubts are cleared, each treatment should be carefully documented and monitored” (23).

While opinions are many and varied, only a few groups have made an adequate effort to acquire firm data on relative benefits and harms. In a randomized study using the anabolic androgen oxandrolone, 32 men aged 60–87 took oxandrolone 20 mg/day for 12 weeks or placebo (24). Oxandrolone produced significant increases in lean body mass and muscle strength during treatment, but 12 weeks after the treatment had ended these measures were no long different from baseline; however, there was some improvement in fat mass during the study, which was largely discernible 12 weeks later. These modest short-term effects hardly seem to provide a justification for anabolic treatment of the elderly in view of the risks involved.

Adverse effects of androgens in women

There are clear differences of opinion about the use of androgens in women. An Australian reviewer has argued that women may have symptoms secondary to androgen deficiency and that “prudent” androgen replacement can be effective in relieving both the physical and psychological symptoms of such insufficiency (25). The reviewer suggested that testosterone replacement for women is safe, with the caveat that doses should be restricted to the “therapeutic” window for androgen replacement in women, such that the beneficial effects on well-being and quality of life are achieved without incurring undesirable virilizing effects. The predominant symptom of women with androgen deficiency is claimed to be loss of sexual desire after a premature or natural menopause, while other indications for androgens include premenopausal iatrogenic androgen deficiency states, glucocorticoid-induced bone loss, management of wasting syndromes, and possibly premenopausal bone loss, premenopausal loss of libido, and the treatment of the premenstrual syndrome.

Some reservations about this approach arise when one considers the possible adverse effects and the doubts that have been raised as to whether there is in fact a safe therapeutic window when treating women with androgens. This comes clearly to the fore in a thoughtful paper by another Australian author, a speech therapist (26). For women treated with androgens or related compounds for any reason, virilization of the voice, which soon becomes permanent, is a distressing complication that has not received a great deal of specific study. This review provides some pointers for clinical practice. She reports on four women aged 27–58 years who sought otolaryngological examination because of significant alterations to their voices, the primary concerns being hoarseness, lowering of habitual pitch, difficulty in projecting their speaking voices, and loss of control over their singing voices. Otolaryngological examination with a mirror or flexible laryngoscope showed no apparent abnormality of vocal fold structure or function, and the women were referred for speech pathology with diagnoses of functional dysphonia. Objective acoustic measures using the Kay Visipitch showed significant lowering of the mean fundamental frequency in each woman, and perceptual analysis of the patien...

Table of contents

• Cover Image
• Table of Contents
• Title
• Copyright
• Preface
• CORTICOSTEROIDS AND RELATED DRUGS
• PROSTAGLANDINS
• SEX HORMONES AND RELATED DRUGS
• IODINE AND DRUGS THAT AFFECT THYROID FUNCTION
• INSULINS AND OTHER HYPOGLYCEMIC DRUGS
• OTHER HORMONES AND RELATED DRUGS
• LIPID – REGULATING DRUGS
• ENDOCRINE AND METABOLIC ADVERSE EFFECTS OF NON-HORMONAL AND NON-METABOLIC DRUGS
• Index of drug names