Side effects of anabolic steroids and contraindications.

The endocrine side effects are mainly androgenic and concern particularly but not exclusively females and children. Depending on individual sensitivity, the dosage used and the androgenicity of the drug concerned, signs of virilization ranging from slight voice disturbances to severe derangement of reproduction can develop, the latter occurring in both sexes. Progestational effects are of little importance. Hepatic alterations are caused almost exclusively by 17 alpha-alkylated steroids and can range from abnormal liver function tests to life-threatening liver tumours. Atherogenic changes in the lipid-lipoprotein balance, again a domain of the 17 alpha-alkylated preparations, might increase the risk of coronary heart disease. The metabolic influences of anabolic compounds can--at excessive dosage levels--create a prediabetic condition and polycythaemia. The influence of anabolic agents on psyche and behavior in normal doses are mostly positive, rendering the drugs useful for adjuvant therapy in patients whose general condition is poor, irrespective of the origin. If given in excessive doses they can cause grave psychic and behavioral disturbances and possibly dependence. Anabolic-androgenic steroids should be used with caution in patients who are particularly sensitive to side effects, where fluid retention must be prevented, in subjects with liver diseases, skeletal metastases of mammary carcinoma, and when longitudinal growth is not completed. They are contraindicated in carcinoma of the prostate and mammary carcinoma in the male and their use should be discouraged in pregnancy and during lactation.

Interactions of anabolic steroids.

Drug-drug interactions, or interference between drugs and other treatments, depend on many factors and are therefore difficult to predict. However, a number are clearly established in the case of anabolic-androgenic steroids. The beneficial interactions between anabolic steroids and radiotherapy or cytostatic drugs respectively are of therapeutic value. Adjuvant treatment with anabolic compounds in patients undergoing radiation and/or cytostatic therapy is beneficial because it can prevent or reduce depression of erythropoiesis, granulopoiesis and thrombopoiesis. It also diminishes protein catabolism, supports recovery, improves the general condition of the patient and minimizes radiation sickness. Potentially adverse interactions with anabolic steroids must be expected in the case of oral anticoagulants and antidiabetic drugs, since sensitivity to each of the latter is increased. This makes it particularly advisable to monitor patients receiving either oral anticoagulants or antidiabetic treatment concurrently with anabolic drugs.

Miscellaneous uses of anabolic steroids.

The original list of indications for anabolic-androgenic steroids has been reduced to those discussed in this publication so far and to mammary carcinoma, deficiency states and growth disorders. In disseminated endocrine-responsive mammary carcinoma in the female, anabolic drugs have a proven palliative effect in some 20 to 40% of patients, arresting tumour growth for up to 12 months and improving the patient's general condition. In high doses they can cause a disturbing increase in libido. Patients with deficiency states can, irrespective of the cause, benefit from adjunctive anabolic steroid treatment, provided their food supply is adequate. Positive effects are exerted by the anabolic agents' protein anabolic and anticatabolic actions, by psychic stimulation of the patient and by enhancement of recovery. Current trials strongly indicate that oral anabolic drugs administered alone or in combination with growth hormone or thyroid preparations are of therapeutic value in growth disorders such as constitutional delay of growth and puberty, hypopituitary dwarfism, chronic renal diseases and in Turner's syndrome.

Development and present state of hormone replacement therapy.

The first therapeutic trials to evaluate the treatment of climacteric symptoms by the administration of ovarian tissue were reported in 1896, i.e. before the endocrine function of the ovary was known or estrogens had been discovered. These were followed by investigations using various ovarian, placental and urine extracts, implantation of ovarian tissue and by oral treatment with dried ovarian tissue. However, reasonably acceptable hormonal drugs did not become available until the third decade of this century, while drugs meeting modern requirements, including that of oral activity, have been available only since the 1940s. It took at least 20 more years before publications for lay people and intensive endocrinological research convinced both the affected women and the medical profession of the value and even the necessity of hormonal treatment for ovarian-deficiency sequelae. Nowadays the treatment of climacteric and post-climacteric symptoms with estrogens and progestogens is a highly effective and indeed common practice. However, their use is of less value for the therapy of post-climacteric cardiovascular diseases and osteoporosis. As regards the latter, it may be said that androgenic-anabolic steroids and Org OD 14, a steroid related to norethynodrel, have usefully extended the available therapeutic armamentarium. Estrogens and progestogens are widely used for the prophylaxis of post-climacteric osteoporosis and cardiovascular diseases because their exceptional efficacy is well proven. Intensive research has resulted in the development of highly effective and virtually harmless hormonal drugs that are available in a great variety of formulations for all possible modes of administration.(ABSTRACT TRUNCATED AT 250 WORDS)

[History of the hormonal treatment of climacteric disease symptoms]. / Zur Geschichte der hormonellen Behandlung klimakterischer Krankheitserscheinungen.

The first trials using oestrogen-containing substances to treat climacteric symptoms were performed as long ago as the end of the last century, when oestrogenic hormones were not yet even known to exist. However, it took a further 60 years or so before oestrogens and other sex hormones such as progestogens and androgens could be prepared in the form of acceptable hormonal drugs. Meanwhile, the use of such drugs and their artificial derivatives for the treatment of climacteric complaints and disorders and the prophylaxis of major postmenopausal diseases has been refined to such a high degree of safety and efficacy that these forms of therapy have become part of the essential medical armamentarium.

An oral contraceptive particularly suitable for women over 35.

PIP: Fertility control for women aged 35 and over is a concern that requires consideration of specific needs and technologies. Orally active steroids are considered the best method available among all the methods of contraception. The steroids are highly beneficial as they are effective and reversible. As well, they prevent the onset of osteoporosis and regulate menstrual bleeding. However, they do hide the symptoms of menopause and along with them come adverse side effects. A study of 434 women by 70 general practitioners and gynecologists was conducted to determine the cycle control and side effects of a combined oral contraceptives (OC). The women, aged 30 and older, were given one tablet containing 0.150 mg desogestrel and 0.020 mg ethinyl estradiol for 21 consecutive days. The results demonstrated the high effectiveness of this combination of desogestrel and ethinyl estradiol as a contraceptive (no pregnancies were recorded). It also proved an acceptable method of cycle control. Formerly, estrogens have been denounced for their side effects, but new compounds have proven effective, safe and beneficial.^ieng

[Metabolic effects of oral contraceptives]. / Stoffwechselwirkungen oraler Kontrazeptiva.

Estrogens and the progestogens of an oral contraceptive can cause metabolic effects either by themselves or in combination with each other. Those induced by progestogens seem to be of particular importance. Influences of both steroids on water und electrolyte metabolism are of little relevance, those on carbohydrate metabolism must be expected in diabetic patients and are possible in high-risk-patients, weight increase may occur. Progestogens with androgenic properties can have important effects on the synthesis of carrier proteins, such as SHBG, and produce a lipid pattern which is usually associated with atherogenesis. Estrogens are rather anti-atherogenic in this respect. Newly developed progestogens seem to lack these possibly life-threatening influences on protein and fat metabolism. Their use might enable the production of oral contraceptives with less side and after-effects.

[Anabolic steroids and sports]. / Anabolika und Sport.

Anabolic steroids are derivatives of androgens with less androgenic and stronger anabolic actions. They should be used for therapeutic indications only. Their misuse to improve physical performance is unethical (doping), illegal and of doubtful pharmacological value. Together with intense muscular exercise and high-protein diet, anabolics due to their anabolic and anti-catabolic actions possibly increase physical performance and enhance recovery in athletes where added strength is a great advantage. In most sport disciplines a beneficial effect has not been demonstrated. Like all active drugs, anabolics can cause side-effects. They depend on structure, dosage and duration of administration. The misuse by athletes of high doses during long periods should be a particular motivation for doctors, teachers and coaches to discourage athletes from using anabolic drugs. The dangers of overdosing and long-term use are emphasized, search for untoward side- and after- effects by regular and careful controls is recommended.

[Unintended effects of oral contraceptives. II. Progesterone-caused effects, interactions with drugs]. / Unbeabsichtigte Wirkungen der oralen Kontrazeptiva. II. Progestagen-bedingte Effekte, Wechselwirkungen mit Arzneimitteln.

A variety of desirable and undesirable side effects of oral contraceptives is attributed to the progestins. The favourable effects can be of considerable importance but are not suitable for therapeutic use. The occurrence of possibly severe adverse side effects, notoriously neglected for years, is increasingly recognized. Some of these potentially serious effects are dose dependent and seem to be structure related. Consequently particular attention is focussed upon newly developed compounds which seem to lack some of such disadvantages. Interactions between oral contraceptives and other drugs are reported; they appear to be of little clinical significance.

[Unintended effects of oral contraceptives. I.Estrogen-related effects]. / Unbeabsichtigte Wirkungen der oralen Kontrazeptiva. I. Ostrogenbedingte Effekte.

Oral contraceptives are almost optimally effective but not yet perfectly safe. They can cause favourable or adverse unintended effects which cannot always be attributed to either the estrogen or the progestagen; however, in many instances a fair differentiation is possible. Type, intensity and frequency of side effects depend on dosage, duration of administration and on the structure of the substance. Some favourable side effects of estrogens are used for therapeutic purposes. Adverse side effects of estrogens are either subjectively disturbing only, or medically important, but few are life threatening. Dose dependence has been established, a structure relationship is unlikely.

The history of anabolic steroids and a review of clinical experience with anabolic steroids.

Metabolism is the term employed to embrace the various physical and chemical processes occurring within the tissues upon which the growth and heat production of the body depend and from which the energy for muscular activity, for the maintenance of vital activity and for the maintenance of vital functions is derived (Best & Taylor 1950). The destructive processes by which complex substances are converted by living cells into more simple compounds are called catabolism. Anabolism denotes the constructive processes by which simple substances are converted by living cells into more complex compounds, especially into living matter. Catabolism and anabolism are part of all metabolic processes, the carbohydrate, fat and protein metabolism. The term anabolic refers only to substances that exert an anabolic effect on protein metabolism and are unlikely to cause adverse androgenic effects. They shift the equilibrium between protein synthesis and degradation in the body as a whole in the direction of synthesis, either by promoting protein synthesis or reducing its breakdown. The protein anabolic effect of anabolic steroids is not restricted to single organs but is the result of stimulated biosynthesis of cellular protein in the whole organism.

[Estrogens and the psyche]. / Oestrogens and Psyche.

Animal experiments have revealed much about location, mode and mechanism of action of oestrogens on the brain. It appears very likely from these experiments that oestrogens affect psychic functions. However, data proving such actions in the human are fragmentary and incomplete. It is generally assumed that physiological concentrations of oestrogens influence sexual and non-sexual behaviour, as well as mental performance in man, but the requisite scientific data are still insufficient in many cases to allow definite conclusions to be reached. Similarly, statements that moderately increased concentrations of oestrogens affect the psyche continue to be a matter of debate. In contrast it is established that both excess and deficiency of oestrogens can influence psychic functions in the human. This has been clearly demonstrated in extensive studies, particularly with regard to the psychic changes in the peri- and postmenopause, whereas little can be said about a cause-effect relationship between oestrogen deficiency and declining mental function with advancing age. The therapeutic value of oestrogen replacement in psychic disturbances associated with oestrogen deficiency states such as hypogonadism, after castration and in the climacteric is well documented by many studies. All other assumed psychic indications in the process of ageing are much less clearly defined and at present of questionable medical importance.

The effect of Bepridil on respiratory and cardiovascular function: a placebo-controlled study.

Bepridil is a novel substance with antianginal and specific antiarrhythmic activities. To investigate its effect on bronchomotor and cardiovascular function a placebo-controlled, randomized, double-blind study was performed in 12 healthy volunteers of both sexes. The test preparations were administered by intravenous infusion. Bepridil was given in a dose of 2 mg/kg, which is sufficient to produce a therapeutic plasma level. With body plethysmography the airway resistance was determined before and 110 min after test drug administration. Oscillatory resistance (Oscillation method, Siregnost FD5, Siemens), blood pressure, and electrocardiogram were recorded before administration of the test preparation and thereafter in short intervals for 20 min and in longer intervals for 2 h. Analysis of the data does not indicate that Bepridil affects respiratory function in other ways than a placebo. Hence Bepridil in therapeutic doses is unlikely to produce untoward effects on the respiratory system. Likewise no unwanted effects on the cardiovascular system were recorded; the observed antitachydardia effect is of therapeutic value. The usefulness of the oscillation method to investigate influences on bronchomotor function has been confirmed.