An orally active selective androgen receptor modulator is efficacious on bone, muscle, and sex function with reduced impact on prostate.

A number of conditions, including osteoporosis, frailty, and sexual dysfunction in both men and women have been improved using androgens. However, androgens are not widely used for these indications because of the side effects associated with these drugs. We describe an androgen receptor (AR) ligand that maintains expected anabolic activities with substantially diminished activity in the prostate. LGD2226 is a nonsteroidal, nonaromatizable, highly selective ligand for the AR, exhibiting virtually no affinity for the other intracellular receptors. We determined that AR bound to LGD2226 exhibits a unique pattern of protein-protein interactions compared with testosterone, fluoxymesterone (an orally available steroidal androgen), and other steroids, suggesting that LGD2226 alters the conformation of the ligand-binding domain. We demonstrated that LGD2226 is fully active in cell-based models of bone and muscle. LGD2226 exhibited anabolic activity on muscle and bone with reduced impact on prostate growth in rodent models. Biomechanical testing of bones from animals treated with LGD2226 showed strong enhancement of bone strength above sham levels. LGD2226 was also efficacious in a sex-behavior model in male rats measuring mounts, intromissions, ejaculations, and copulation efficiency. These results with an orally available, nonaromatizable androgen demonstrate the important role of the AR and androgens in mediating a number of beneficial effects in bone, muscle, and sexual function independent from the conversion of androgens into estrogenic ligands. Taken together, these results suggest that orally active, nonsteroidal selective androgen receptor modulators may be useful therapeutics for enhancing muscle, bone, and sexual function.

Randomized comparison of megestrol acetate versus dexamethasone versus fluoxymesterone for the treatment of cancer anorexia/cachexia.

PURPOSE: Previous double-blind, placebo-controlled, randomized clinical trials have demonstrated that both corticosteroids and progestational agents do partially alleviate cancer anorexia/cachexia. Pilot information suggested that an anabolic corticosteroid might also improve appetite in patients with cancer anorexia/cachexia. The current trial was developed to compare and contrast a progestational agent, a corticosteroid, and an anabolic corticosteroid for the treatment of cancer anorexia/cachexia. PATIENTS AND METHODS: Patients suffering from cancer anorexia/cachexia were randomized to receive either dexamethasone 0. 75 mg qid, megestrol acetate 800 mg orally every day, or fluoxymesterone 10 mg orally bid. Patients were observed at monthly intervals to evaluate weight changes and drug toxicity. Patients also completed questionnaires at baseline and at monthly intervals to evaluate appetite and drug toxicities. RESULTS: Fluoxymesterone resulted in significantly less appetite enhancement and did not have a favorable toxicity profile. Megestrol acetate and dexamethasone caused a similar degree of appetite enhancement and similar changes in nonfluid weight status, with nonsignificant trends favoring megestrol acetate for both of these parameters. Dexamethasone was observed to have more corticosteroid-type toxicity and a higher rate of drug discontinuation because of toxicity and/or patient refusal than megestrol acetate (36% v 25%; P =.03). Megestrol acetate had a higher rate of deep venous thrombosis than dexamethasone (5% v 1%; P =.06). CONCLUSION: Whereas fluoxymesterone clearly seems to be an inferior choice for treating cancer anorexia/cachexia, megestrol acetate and dexamethasone have similar appetite stimulating efficacy but differing toxicity profiles.

Rat liver lysosomal and mitochondrial activities are modified by anabolic-androgenic steroids.

PURPOSE: The aim of this study was to examine the separate and combined effects of an 8-wk treatment with high doses of 17alpha-alkylated anabolic-androgenic steroids (AAS) and exercise training on selected lysosomal and mitochondrial enzyme activities in rat liver. METHODS: Sedentary and treadmill-trained (25 m x min(-1), 45 min x d(-1), 5 d x wk(-1)) male rats were treated with fluoxymesterone, methylandrostanolone, or stanozolol (2 mg x kg body weight(-1), 5 d x wk(-1)) for 8 wk. RESULTS: Acid phosphatase, arylsulfatase, beta-glucuronidase, and beta-galactosidase activities were increased in liver homogenates of sedentary and trained AAS-treated rats. The mitochondrial respiratory chain activities rotenone-sensitive NADH-cytochrome c reductase (NCCR), succinate cytochrome c reductase (SCCR), and cytochrome oxidase (COX) showed a significant decrease in steroid-administered rats, whereas citrate synthase (CS), a matrix enzyme, exhibited no changes in activity, pointing to a selective effect of AAS on mitochondrial membrane complexes. In vitro studies in mitochondrial fractions isolated from the liver of control rats showed that COX and CS activities were insensitive to the AAS, whereas NCCR and SCCR activities were partly inhibited. On the other hand, the mean values of serum parameters related to hepatic function were within normal ranges in all the experimental groups of animals. CONCLUSIONS: The present data show that 8-wk ingestion of three different anabolic-androgenic steroids, either with or without concurrent exercise training, affects lysosomal hydrolases and mitochondrial respiratory chain electron transport in rat liver without modifying classical serum indicators of hepatic function.

Decreased levothyroxine requirement in women with hypothyroidism during androgen therapy for breast cancer.

OBJECTIVE: To determine the effects of androgen administration on measures of thyroid function and thyroid hormone replacement doses in women with breast cancer. DESIGN: Consecutive patients with metastatic, hormone-dependent breast cancer who were eligible for androgen treatment. INTERVENTIONS: Androgen therapy (fluoxymesterone, 10 mg orally twice daily) was continued for as long as it was effective in controlling tumor growth. PATIENTS: 7 patients with no known thyroid disease and 4 others receiving long-term treatment for hypothyroidism. MEASUREMENTS: Serum levels of total and free thyroxine (T4), thyroid-stimulating hormone (TSH), and T4-binding globulin were determined before and every 4 weeks after androgen therapy was initiated. RESULTS: Within 4 weeks of androgen administration to the seven patients without thyroid disease, serum levels of total T4 and T4-binding globulin decreased (P < 0.001), whereas the calculated free thyroxine index and measured free hormone levels remained unchanged. Six to 12 weeks after androgen therapy was discontinued, all seven patients remained clinically euthyroid, and serum levels returned to baseline values. In contrast, clinical hyperthyroidism developed shortly after androgen was administered to four patients who received long-term thyroid hormone replacement therapy. Within 4 weeks of treatment, the serum free T4 level increased in each of the four patients, whereas the TSH level decreased. Thyroid hormone doses had to be reduced by 25% to 50% to maintain euthyroidism. CONCLUSIONS: The study documents the reversible effects of androgens on thyroid hormone levels and indicates the need to reduce thyroid replacement doses in women during androgen therapy. Monitoring thyroid hormone levels in patients receiving replacement therapy and perhaps in those with autonomous thyroid function is necessary after androgen therapy.

Adult height in girls with Turner syndrome treated with low-dose estrogens and androgens.

OBJECTIVE: To determine if low dosages of estrogens and androgens administered to girls with Turner syndrome adversely affected their adult height. DESIGN: A nonrandomized control trial of nine girls. SETTING: The endocrine clinic at Texas Children's Hospital in Houston, Texas, an academic referral center. PARTICIPANTS: Participants had chromosomal defects consistent with Turner syndrome. Informed consent was obtained in accordance with institutional review board procedures. Eligibility criteria included an absence of previous hormone treatment. No one withdrew from this study because of adverse effects. INTERVENTIONS: Hormonal replacement therapy was initiated with conjugated estrogen 0.15 mg and fluoxymesterone 1 mg administered daily. MAIN OUTCOME MEASURES: Outcome measurements were a comparison of the final heights following treatment versus the predicted adult heights prior to treatment. RESULTS: The predicted adult height in these children prior to treatment was 140.0 +/- 4.4 cm (mean +/- SD); the actual adult height was 139.63 +/- 4.1 cm. The difference was 0.37 +/- 3.54 cm, which was not statistically significant by Wilcoxon signed-rank test (p = 0.23). The 95% confidence interval on this difference ranged from -3.1 to 2.3 cm, which indicates a true mean height loss of no more than 3.1 cm or a true mean gain of no more than 2.3 cm. CONCLUSIONS: Our results indicate that hormone replacement therapy with low dosages of conjugated estrogens and androgens starting at 10-11 years of age in children with Turner syndrome does not adversely affect actual adult height.

Aberrant androgen action and increased size of tandem CAG repeat in androgen receptor gene in X-linked recessive bulbospinal neuronopathy.

Plasma levels of testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) after 3 or 6 days of administration of the synthetic androgenic hormone fluoxymesterone (10 mg/day) were measured in 26 patients with X-linked recessive bulbospinal neuronopathy (X-BSNP) and 22 age-matched male controls. The testosterone, LH and FSH levels in the controls were markedly suppressed after administration, but in the patients with X-BSNP, they were suppressed significantly less. The level of suppression varied considerably with the patients, and those of plasma testosterone and FSH were significantly correlated with the number of CAG repeats in the androgen receptor gene. These findings suggest that the androgen action was aberrantly transduced in the target organs in the patients with X-BSNP and which is related to the elongated CAG repeat in the androgen receptor gene.

Ultrastructural changes induced by anabolic steroids in liver of trained rats.

The effects of anabolic steroid treatment in association with endurance training on biochemical serum parameters and liver ultrastructure have been investigated in male rats. Values of serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase were not significantly affected by administration of high doses of fluoxymesterone or methylandrostanolone. Electron microscopic examination of hepatic tissue from treated animals revealed ultrastructural alterations of hepatocytes. The most prominent changes were swelling of mitochondria, which presented electron-lucent matrix and slightly defined cristae, and a marked increase in the number of lysosomes. These changes were evident in both sedentary and trained treated rats, indicating that liver cell damage is produced by anabolic-androgenic steroids despite the simultaneous realization of physical exercise. The alterations observed were not detected by means of conventional biochemical liver tests.

Effect of training and anabolic-androgenic steroids on drug metabolism in rat liver.

The effects of anabolic-androgenic steroid administration and exercise training on various aspects of hepatic function were investigated in sedentary and trained (treadmill for 12 wk) male and female rats treated orally with fluoxymesterone or methylandrostanolone (2 mg.kg-1 body weight, 5 d.wk-1 for 8 wk). The mean values of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total and direct bilirubin, and total- and high-density lipoprotein-cholesterol remained within normal range in all groups of male animals. The same is true for female rats, except for an increase in alkaline phosphatase activity in the steroid-treated groups. Hepatic microsomal aniline p-hydroxylase activity was reduced in male and increased in female rats by either steroid, whereas no significant effect was detected on 7-ethoxycoumarin deethylase activity. The levels of cytochrome P-450 and cytochrome b5 were markedly decreased by the anabolic-androgenic steroid treatment in male rat microsomes, but neither the steroid administration nor exercise training induced significant changes in the cytochrome levels of female rat livers. Taking into account the significant increase in microsomal protein yield elicited by fluoxymesterone or methylandrostanolone treatment both in males and females, it is noteworthy that the total monooxygenase activities and cytochrome P-450 content, expressed on a per gram liver basis, were significantly increased in female whereas they were apparently unchanged in male rats. In conclusion, the present data show that the prolonged ingestion of high doses of anabolic-androgenic steroids, either with or without concurrent exercise training, can modify in a sex-dependent manner the capacity of rat liver to metabolize drugs without affecting classical serum indicators of hepatic function.

Long-term results of treatment with low-dose fluoxymesterone in constitutional delay of growth and puberty and in genetic short stature.

This prospective study was designed to assess growth response, side effects, other possible long-term effects, and final adult height in boys treated with the oral androgen, fluoxymesterone. From 1973 to 1984, eighty-two short boys (71 with constitutional delay of growth and puberty [CDGP] and 11 with genetic short stature [GSS]) were treated with daily oral doses of 2.5 mg of fluoxymesterone from 6 to 60 months. Final height assessment was made from 1989 to 1991. A group of 34 untreated boys (26 with CDGP and 8 with GSS) were also followed to assess the accuracy of the Greulich-Pyle and Bayley-Pinneau (GP-BP) and sexual maturity index height prediction methods. During treatment, each patient had a 1.7- to 2.5-fold increase in linear growth velocity. Accelerated velocity (over baseline) continued as long as the bone age was less than 14 years. No adverse androgenic effects (or undue acceleration of puberty) were observed. Final height exceeded pretreatment predictions for CDGP + GSS by 6.1 +/- 3.5 (SD) cm (GP-BP) and 5.4 +/- 3.2 cm (sexual maturity index). It is concluded that a daily oral dose of 2.5 mg of fluoxymesterone can be used to accelerate linear growth in boys with CDGP and GSS when needed to alleviate emotional problems secondary to slow growth and short stature without fear of compromising final adult height.

Effect of prepubertal gonadectomy and sex steroid treatment on the growth and lymphocyte populations of the rat thymus.

The age at which rats are most sensitive to prepubertal gonadectomy, in terms of thymic growth, was investigated. Gonadectomy enhanced thymic growth at each age; the greatest difference in thymic weight between gonadectomized and intact animals occurred in male rats gonadectomized at 5 weeks of age (64%) and in female rats gonadectomized at 4-5 weeks of age (43-46%). The effect of various synthetic sex steroids on growth and lymphocyte populations of the thymus in gonadectomized rats was examined. Diethylstilboestrol, 1 mg per animal, inhibited thymic growth by more than 35% in both males and females. Ethinyloestradiol, 40 micrograms per animal, inhibited thymic growth by 26% in males but by only 4% in females. Fluoxymesterone, 10 mg per animal, inhibited thymic growth by more than 46% in both sexes. Norgestrel, 12 micrograms per animal, had no effect on thymic growth. The synthetic steroids that significantly inhibited thymic growth decreased the intensity and altered the localization of staining for total T cells (antibody clone MRC OX 19), T helper cells and macrophages (W 3/5), T cytotoxic/suppressor cells (MRC OX 8) and B cells (MRC OX 12).

The effect of anabolic-androgenic steroids on primary myocardial cell cultures.

Although recent case reports suggest that anabolic-androgenic steroids may be directly injurious to the cardiovascular system, the direct myocardial cellular consequences of abuse of these drugs are not known. Therefore, the purpose of this study was to describe the concentration- and time-dependent effects of testosterone cypionate (TC), stanozolol (S), and fluoxymesterone (F) on primary myocardial cell cultures. Evaluation of drug effects were made in 4-d-old primary myocardial cell cultures obtained from 3- to 5-d-old Sprague-Dawley rats. The cultures were exposed to 1 x 10(-4) M, 1 x 10(-6) M, and 1 x 10(-8) M concentrations of TC, S, and F each for 1, 4, and 24 h. Cellular injury was evaluated by alterations in beating activity, induction of morphological alterations, lactate dehydrogenase (LDH) release, neutral red retention, and tetrazolium (MTT) formazan production. Significant alterations in beating activity were observed in the 1 x 10(-4) M TC group in which no beating activity was seen at 1, 4, and 24 h. Morphological integrity was disrupted for the 1 x 10(-4) M TC group at 24 h where destruction of the monolayer was observed. Unlike the cultures treated with the three concentrations of both S and F, significant LDH release was seen at 4 and 24 h with those cultures exposed to 1 x 10(-4) M TC. In the evaluation of neutral red retention, 1 x 10(-4) M TC at 24 h showed a significant decrease in ability to retain the dye.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment with anabolic steroids increases the activity of the mitochondrial outer carnitine palmitoyltransferase in rat liver and fast-twitch muscle.

Treatment of male rats with the anabolic steroids fluoxymesterone or methylandrostanolone increased the activity of the outer carnitine palmitoyltransferase in liver and fast-twitch muscle mitochondria. This effect was not potentiated by physical exercise and was not observed in heart and slow-twitch muscle mitochondria. Anabolic steroids did not affect the sensitivity of the liver enzyme to inhibition by malonyl-CoA. The data presented herein suggest that androgens may have an important physiological role in the regulation of fatty acid oxidation in liver and fast-twitch muscle mitochondria. In addition, our results are at odds with the notion that (most of) the metabolic effects of anabolic steroids on muscle are only evident when physical training is parallely performed.

Effect of anabolic steroids on mitochondria and sarcotubular system of skeletal muscle.

Soleus and extensor digitorum longus (EDL) mitochondria and sarcotubular system were examined in sedentary and trained (treadmill for 12 wk) male rats that were treated with fluoxymesterone or methandrostanolone (2 mg/kg, 5 days/wk, for 8 wk). Neither physical exercise nor anabolic/androgenic steroid administration resulted in a significant change in muscle wet weight. Treatment with the anabolizing androgens increased succinate dehydrogenase activity in fast-twitch muscle mitochondria; this effect was not enhanced by training and was not observed in soleus mitochondria. On the other hand, the content of the slow-twitch muscle in sarcotubular fraction was increased in sedentary rats by fluoxymesterone or methandrostanolone treatment, whereas no significant changes were found in EDL. The training program affected adenosinetriphosphatase (ATPase) activities in the sarcotubular fraction; Mg2(+)-ATPase was increased in both soleus and EDL, but Ca2(+)-ATPase was decreased only in soleus. However, in sedentary animals only the Mg2(+)-dependent activity of EDL was increased by anabolizing androgen treatment, and this change was not potentiated by additional training. The present data indicate that anabolic/androgenic steroids can affect mitochondrial and sarcotubular enzymes in skeletal muscle. The effects are muscle-type specific.

Androgens directly stimulate proliferation of bone cells in vitro.

This report describes the first observation of a direct mitogenic effect of androgens on isolated osteoblastic cells in serum-free culture. [3H]thymidine incorporation into DNA and cell counts were used as measures of cell proliferation. The percentage of cells that stained for alkaline phosphatase was used as a measure of differentiation. Dihydrotestosterone (DHT) enhanced mouse osteoblastic cell proliferation in a dose dependent manner over a wide range of doses (10(-8) to 10(-11) molar), and was maximally active at 10(-9) M. DHT also stimulated proliferation in human osteoblast cell cultures and in cultures of the human osteosarcoma cell line, TE89. Testosterone, fluoxymesterone (a synthetic androgenic steroid) and methenolone (an anabolic steroid) were also mitogenic in the mouse bone cell system. The mitogenic effect of DHT on bone cells was inhibited by antiandrogens (hydroxyflutamide and cyproterone acetate) which compete for binding to the androgen receptor. In addition to effects on cell proliferation, DHT increased the percentage of alkaline phosphatase (ALP) positive cells in all three bone cell systems tested, and this effect was inhibited by antiandrogens. We conclude that androgens can stimulate human and murine osteoblastic cell proliferation in vitro, and induce expression of the osteoblast-line differentiation marker ALP, presumably by an androgen receptor mediated mechanism.

Effects of human chorionic gonadotropin, androgens, adrenocorticotropin hormone, dexamethasone and hyperprolactinemia on plasma sex steroid-binding protein.

This presentation reports the effects of androgens, glucocorticoids and some pituitary hormones on plasma sex steroid-binding protein (SBP). The latter was measured by a solid phase method after desteroidation of the plasma. An hCG test (1500 I.U. every other day X 7) was given to 60 boys. In the children with a normal testosterone (T) rise, plasma SBP decreased (% of basal values) either significantly (38.3 +/- 9.3%, group A; n = 29), or moderately (13.4 +/- 4.4%, group B; n = 9) or did not change (-1.6 +/- 6.4%, group C; n = 10). In the 3 infants tested at an age when SBP normally rise sharply, hCG partially prevented this rise. The administration of either fluoxymesterone (10 mg/m2 for 10 days) or depot-T (4 I.M. injections of 100 mg/m2 every 2 weeks) induced a significant drop (about 2-fold) in plasma SBP in a control group of infants or children, but did not change SBP in 3 infants with the androgen insensitivity syndrome. A single injection of 0.25 mg of ACTH did not significantly alter SBP levels. In contrast, at the end of a 3-day ACTH test (0.5 mg/m2 12 hourly X 6) SBP levels had significantly decreased (mean 35% fall) with no age or sex differences, and with no correlation with the cortisol levels reached. However, the lowering effect of ACTH on SBP levels is likely mediated by glucocorticoids, since its effect was reproduced by high doses (8 mg/day for 3 days) of dexamethasone given at once or after 3 days of treatment at lower dose (20 micrograms/kg BW). It would appear that the depressive effect of ACTH and/or dexamethasone is observed for a threshold dose of glucocorticoids (greater than 5-fold physiological levels) and a certain time (greater than or equal to 3 days) of exposure. The mechanism by which androgens and glucocorticoids lower SBP levels in vivo is not yet understood. From recent experiments, showing that both stimulate the secretion of SBP in hepatoma cells in vitro, it would appear that both hormones may alter SBP metabolism. In a selected population of hyperprolactinemic women, with normal weight and no hirsutism, plasma SBP levels were found in the normal female range. The discrepancy with previous studies in the literature may be explained by differences in the degree of hyperprolactinemia and/or associated hyperandrogenim. This study further documents the multifactorial and intricated hormonal influences involved in the regulation of plasma SBP in vivo.

Lack of effect of anabolic steroids on specific mRNAs of skeletal muscle undergoing compensatory hypertrophy.

Compensatory hypertrophy of the fast-twitch plantaris muscle (HP) was induced in male rats to determine whether the resulting translational activity of isolated polyribosomes could be modified in this process and by the androgen status. HP induced a significant increase in free androgen binding sites and a typical protein synthesis pattern characterized by a slow myosin light chain isozyme (LC-1S), an increase in fast isozymes (LC-1F,2F) and of beta-tropomyosin/alpha-tropomyosin ratio. The variations in receptor occupancy following castration and treatments with four anabolic steroids (AS) did not result in modification of the template activity of major HP mRNAs. These data suggest that the slight increase of steroid receptors found in HP remains insufficient to trigger an androgenic response in skeletal muscle.

Sex mediated lipid metabolism in human aortic smooth muscle cells.

When human aortic smooth muscle cells in culture were treated with pharmacological doses of estrogen and testosterone for 48 hrs, the rate of cholesterol synthesis measured both by acetate incorporation and the 3, hydroxy 3-methylglutaryl Co enzyme A reductase (HMG-CoA) activity declined significantly as compared to control. However, the rate of cholesterol esterification increased by 132% and 45% in response to testosterone and estrogen respectively. Also, acetate incorporation into fatty acids and fatty acid synthetase enzyme activity increased by hormonal treatment but remained in the free form especially by estrogen. Testosterone treatment resulted in more esterification (p less than .025) of fatty acid than estrogen treatment. Incubation with hormones for 48 hrs resulted in enhanced uptake of 14C-labeled cholesterol along with increased accumulation of cellular cholesterol. Increased synthesis of phospholipid and triglyceride by estrogen may be responsible for excretion of cellular sterol and fat. These results indicate that sex-hormones have an important effect on the regulation of lipid metabolism in human aortic cells.

Androgen depletion and repletion as a means of potentiating the effect of cytotoxic chemotherapy in advanced prostate cancer.

Seventy-five patients with stage D-2 prostate cancer refractory to orchiectomy have been entered in a controlled trial to test whether androgen priming enhances the efficacy of chemotherapy. All patients are treated with aminoglutethimide and hydrocortisone as a means of achieving medical adrenalectomy and are given cyclic i.v. chemotherapy with cytoxan, adriamycin and 5-fluorouracil. Patients in the stimulation arm (N = 39) receive, in addition, fluoxymesterone (5 mg p.o. b.i.d.) for 3 days before and on the day of chemotherapy. A similar response rate was observed in the stimulation and control arm (83% vs 74% respectively) when the analysis was restricted to evaluable patients. When all patients were included, a significantly higher response rate was observed in the control arm (64% vs 49%, P less than 0.05) as a result of the larger fraction of unevaluable patients in the stimulation arm (41% vs 14%). Median duration of response is 9 months in the stimulation and 10 months in the control arm. Median overall survival in the stimulation and control group is 12 months and 16 months respectively. Significant toxicity consisting of exacerbation of bone pain and, in two patients, development of reversible spinal cord compression was observed following androgen priming. Our results suggest that combined medical adrenalectomy and chemotherapy are highly effective in the treatment of advanced prostate cancer. Thus far, no additional benefit has been observed with androgen priming.

Stimulatory effects of androgens on normal children's bone marrow in culture: effects on BFU-E, CFU-E, and uroporphyrinogen I synthase activity.

We studied the effect of natural and synthetic androgens on children's erythropoietic precursor cells in culture. Cultures of normal marrow were carried out according to a miniaturized methylcellulose method in the presence of erythropoietin. We then evaluated the effects of testosterone, nortestosterone, fluoxymesterone and etiocholanolone (10(-9)-10(-6) M) on erythroid colony-forming units (CFU-E) and burst-forming units (BFU-E). Androgen-induced growth of erythroid progenitors was quantified by directly scoring colonies and by a biochemical determination of the uroporphyrinogen I synthase activity (UROS). We observed a significant increase (p less than or equal to 0.05) in the number of CFU-E and BFU-E and in the UROS activity of derived colonies in the presence of androgens (10(-8) or 10(-7)M). This microculture assay could be useful not only to study the effect of androgens on erythroid progenitor cells in culture, but also to predict the best androgenic treatment of anemia in children and adults.