Nervous system An old indication for anabolic steroids, still followed in a few centers, is the treatment of aplastic anemia. A 40-year-old Korean woman who had taken oxymetholone for aplastic anemia (doses not stated) developed cerebral venous thrombosis accompanied by a tentorial subdural hematoma (99Ar).
Hiccups have been classified as a neurological reaction that can be triggered by many factors. There have been a few published reports of persistent hiccups associated with oral and intravenous corticosteroids and one of progesterone-induced hiccups, which were thought to be secondary to the glucocorticoid-like effects of progesterone on the brainstem.
• Anabolic steroid-induced hiccups have now also been reported in a champion power lifter (100Ar). The hiccups occurred within 12 hours of an increase in the dose of oral methandrostenolone from 50 mg to 75 mg dd, and persisted for 12 consecutive hours until medical attention was sought. The hiccups abated rapidly after the dose of methandrostenolone was reduced, but he was unwilling to abandon it completely.
Drug abuse Although androgenic anabolic steroids have largely disappeared from routine medical practice their adverse effects continue to merit study, if only because papers still appear promoting their prolonged use in patients who are seriously ill and may therefore be particularly likely to develop adverse effects. Recently proposed indications include Duchenne's muscular dystrophy and the severe anemia that can occur in patients on dialysis. In addition there is a persistent illegal market in these compounds, to promote physical strength. A difficulty in determining the ultimate consequences of anabolic steroid abuse for body-building or to advance sporting achievement is that individuals prone to such abuse may well have taken several different types of substance at the same time or in succession. Indeed, an analysis of the hair of seven body builders showed what the authors termed a "complete pharmacopeia" of drug residues, ranging from cor-ticosteroids, anabolic steroids, and androgens to beta-adrenoceptor agonists, antidepressants, diuretics, and human chorionic gonadotrophin (101c).
In one case a partial empty sella syndrome occurred in an elite 39-year-old body-builder with a 17-year history of drug abuse involving growth hormone, anabolic steroids, testosterone, and thyroid hormone (102A). The pituitary is a hormone-responsive gland, but it has not previously been shown to suffer negative feedback in response to any of these substances. Various of them could in principle have contributed to the effect, or it could have been an indirect consequence of drug abuse, by way of an increase in intracranial pressure, which is a known cause of empty sella syndrome.
Apart from the physical effects of exogenous anabolics and androgens, they can also have behavioral effects, including promotion of sexual behavior (which may or may not be regarded as an unwanted effect) and perhaps enhanced aggressiveness. However, most of the evidence on the latter is derived from raised concentrations of endogenous testosterone. Men who use androgenic anabolic steroids to enhance their sporting achievements seem to be more likely to have cyclic depression, but young men who have stopped using anabolic steroids can also develop depression and fatigue as withdrawal effects (103r).
ANTIANDROGENS (SED-14,1475; SEDA-23, 445; SEDA-24, 479; SEDA-25, 494)
In reviews of various means of treating locally advanced prostatic cancer it has been concluded that, compared with castration and other methods, monotherapy with a non-steroidal an-tiandrogen ensures a comparable survival rate and offers potential advantages with respect to maintenance of sexual interest and physical capacity (104r-106r). Bicalutamide 150 mg/day maintains bone mineral density and is well tolerated; gynecomastia and breast pain, common adverse effects of antiandrogens, can be managed by prophylactic irradiation or surgery. LHRH agonists are comparable to surgical castration, but are also associated with an initial flare-up of symptoms and signs of the disease that require treatment with antiandrogens.
For the treatment of the most advanced cases of prostatic cancer, antiandrogen monotherapy has not been consistently proven to be equivalent to surgical castration or complete androgen blockade, but still has the advantage that sexual function can be preserved.
It is common to use a combination of treatments, but there are alternative approaches. Initial treatment with, for example, polyestradiol phosphate every 2 weeks for 8 weeks can be followed by monthly subcutaneous injections. If complete androgen ablation is unavoidable, it can be achieved by either bilateral orchidec-tomy or triptorelin 3.75 mg/month, which can be combined with the anti-androgen flutamide 250 mg tds. This usually causes severe deprivation symptoms (primarily hot flushes), and a Swedish group has sought to quantify these in 915 men (107C). At 18.5 months the incidence of hot flushes was 30% in men who received polyestradiol phosphate and 74% in those who had had complete androgen ablation. In those who used polyestradiol phosphate the frequency of hot flushes and the accompanying distress were also significantly less than in the androgen ablation group. The hot flushes later disappeared in 50% of the men taking polyestradiol phosphate, but the problem was unchanged in those who had had androgen ablation. Similarly promising findings have been reported by Japanese workers who combined flutamide with other LH-releasing hormone agonists (leuprorelide or goserelin) (108c).
The effects of androgen deprivation on bone mineral density are of particular concern because of their physical consequences. The effects of radical androgen deprivation treatment on bone density in the hip and spine have been evaluated for up to 10 years in 36 patients in a cross-sectional study (109c). Hip bone density was significantly lower in patients on deprivation therapy; after a number of years bone density averaged only 55% of that in controls and loss was still continuing at 10 years. The loss was more dramatic in patients who had undergone surgical castration than in those who received medical deprivation treatment, and by 6 years it was least pronounced in those patients in whom intermittent drug treatment had been used.
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