Effects Of Androgen Deficiency Research Articles

Effects of androgen deficiency on the structure of endometrium in women of reproductive age

Objective — to identify the features of the histological structure of the endometrium in women of reproductive age with hypoandrogenism, to optimize therapeutic tactics at the preconceptive stage.
 Materials and methods. Examination of patients with androgen deficiency revealed 48 patients with endometrial hypoplasia by ultrasound markers. After examination on CD 138 and detection of chronic endometritis, 9 patients were excluded from the study. At second stage, immunohistochemical testing for estrogen, progesterone and androgen receptors was performed. According to the results, patients were divided into 2 groups: the first group (24 patients) with a high level of expression of androgen receptors and the second group (15 patients) with a low level of expression of androgen receptors. Both groups of patients received hormonal therapy for 3 months: estradiol valerate 1 g per day continuously and 200 mg of micronized progesterone from the sixteenth to the twenty-fifth day of the menstrual cycle, patients of the first group received additional dehydroepiandrosterone (DHEA) in a dose of 25 mg per day in the form of sublingual spray.
 Results. According to the ultrasound study in the first group of patients, the endometrium was normal both during treatment and 1 and 3 months after stopping treatment. The endometrium of women in group 2 showed positive changes during treatment (control after 1 and 3 months of therapy), and the absence of these effects after discontinuation of hormone therapy, which coincided with the restoration of intermenstrual bleeding in these women.
 Conclusions. Optimization of the gravidar transformation of the endometrium of women with biochemically diagnosed hypoandrogenism and infertility requires study of the receptor potential of the endometrium. The established high levels of expression of androgen receptors at immunohistochemical examination of the endometrium can be considered as indication for the inclusion of DHEA spray forms in the complex of pre-pregnancy training. The combination of estrogen-progestogen therapy and androgens has a positive effect on the gestational potential of the endometrium in women of reproductive age with androgen deficiency.

THE IMPACT OF CENTRAL DEPRIVATION OF TESTOSTERONE ON THE STRUCTURE OF RED BONE MARROW IN MONOCYTOPOESIS IN THE EARLY TERMS OF THE EXPERIMENT

The effect of androgen deficiency on haematopoiesis has not been sufficiently studied yet. It is known that androgens have a double effect on the hematopoietic system. Hematopoietic tissue is a continuously regenerating dynamic system; therefore, the issues of hematopoietic kinetics and its regulation are key ones to understand the pathogenesis of blood diseases in general. It has been determined that the development of all hematopoietic cells results from the proliferation and differentiation of a single pluripotent blood stem cell under the influence of surrounding cells. The effect of prolonged central deprivation of testosterone synthesis on morphological changes in hematopoietic organs is still not enough described in the scientific literature. The aim of this study is to evaluate the microscopic structure of hematopoietic cells in rats during the central deprivation of testosterone synthesis by diferelin injection on the 30 day of the experiment. Materials and methods. The experiment was performed on 20 adult male white rats divided into 2 groups of 10 animals in each group: control and test group. The animals in the experimental group were injected with diferelin (Triptorelin embonate) subcutaneously in a dose of 0.3 mg of active substance per kg / body wt. The rats in the control group received a saline injection. The experiment lasted 30 days. Results. The morphological study of the red bone marrow in the test group of animals on the 30 day of the experiment has demonstrated the structure of the organ is represented by two components: stromal and parenchymal. The stroma consists of reticular cells forming a network of reticular fibbers, most of which are threaded with sinusoidal capillaries. In the middle of the capillaries there is a dense arrangement of erythrocytes in the form of a "column of coins". The pericapillary space is filled with hematopoietic cells at different stages of differentiation. The monoblastic clone is represented by monocyte cells, promonocytes, monoblasts, and progenitor cells that are of the same mophrological structure and structure under light microscopy.

Влияние андрогенного дефицита на состояние углеводного обмена у мужчин

Влияние андрогенного дефицита на состояние углеводного обмена у мужчин

Андрогенный дефицит у пациентов с заболеваниями предстательной железы

Negative effects of androgen deficiency in males can be avoided by regular androgen screening in patients over 50 years of age. We measured testosterone levels in 521 men aged between 18 and 93 years (mean age 60.94 years). A total of 235 patients (45.2%) were found to have age-related hypogonadism. We have developed a diagnostic algorithm for androgen deficiency at outpatient facilities. We also assessed the prevalence of prostatic diseases and a number of somatic disorders in patients with age-related hypogonadism. We have proposed a variant of medical correction of androgen deficiency. Key words: age-related hypogonadism, testosterone, prostate, screening, androgen replacement therapy

Effect of ostarine (enobosarm/GTX024), a selective androgen receptor modulator, on adipocyte metabolism in Wistar rats.

Synthetic ligands of androgen receptor (AR) are a standard in the treatment of androgen deficiency. One of the effects of androgen deficiency is the disturbance in the homeostasis of lipid metabolism. Till date, there are no effective compounds developed to treat androgen deficiency without having any side effects. Nonsteroidal selective androgen receptor modulators (SARMs) are a promising solution for various clinical indications. In this study, we investigated the effect of ostarine (enobosarm), a nonsteroidal SARM, on the rat adipocyte metabolism using in vitro techniques. Isolated rat adipocytes were incubated in the presence of different concentrations of ostarine. Control incubation with testosterone as the natural ligand for AR was performed. AR inhibitors were used to investigate the genomic activity of ostarine. Changes in the intensity of lipolysis, lipogenesis, and the secretion of leptin and adiponectin were measured. Moreover, the gene expression of leptin and adiponectin was assessed. For the first time, we have shown that ostarine has a significant effect on the intensity of lipid metabolism. Ostarine downregulates the expression of leptin and adiponectin mRNAs, as well as decreases their release from rat adipocytes. According to our results, ostarine acts via AR with a similar effect as testosterone in the regulation of lipid metabolism and endocrine function of mature rat adipocytes in vitro. Our results indicate the need for further studies on the effects of SARM on the whole organism.

Alterations in luteal production of androstenedione, testosterone, and estrone, but not estradiol, during mid- and late pregnancy in pigs: Effects of androgen deficiency

Recently, we have found that flutamide-induced androgen deficiency altered progesterone production in the porcine corpus luteum (CL) during mid- and late pregnancy. Herein, we tested whether flutamide administration subsequently influences androgen and estrogen metabolism in the CL of pregnancy. Pregnant gilts were treated with flutamide between Days 43 and 49 (GD50F), 83 and 89 (GD90F), or 101 and 107 (GD108F) of gestation. Corpora lutea (CLs) were collected from treated and nontreated (control) pigs. The concentrations of androstenedione (A4), testosterone (T), estrone (E1), and estradiol (E2) together with the levels of expression of mRNAs and proteins for cytochrome P450 17α-hydroxylase/c17-20 lyase (CYP17A1), 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1), cytochrome P450 aromatase (CYP19A1), and 17β-hydroxysteroid dehydrogenase type 7 (17β-HSD7) were measured in the CL of control and flutamide-treated animals. Steroidogenic enzymes were also immunolocalized in luteal tissues. The luteal concentrations of A4 and T were higher in the GD50F (P = 0.006, P = 0.03) and GD108F (P = 0.005, P = 0.035) groups, but lower in the GD90F (P = 0.004, P = 0.014) group. The E1 level was greater only in the GD90F (P = 0.03) and GD108F (P = 0.035) groups, whereas E2 concentration was not affected by flutamide treatment. Increased luteal CYP17A1 mRNA and protein expression was found in the GD50F (P = 0.002, P = 0.03) and GD108F (P = 0.0026, P = 0.03) groups, but reduced in the GD90F (P = 0.002, P = 0.03) group. mRNA of 17β-HSD1 was upregulated in the GD50F (P = 0.0005) group, but downregulated in the GD90F (P = 0.002) and GD108F (P = 0.0005) groups. In contrast, 17β-HSD1 protein expression was higher in the GD50F and GD108F (P = 0.03) groups, but lower in the GD90F (P = 0.03) group. Both CYP19A1 mRNA and protein levels were greater in the GD90F (P = 0.001, P = 0.028) and GD108F (P = 0.005, P = 0.03) groups. Neither 17β-HSD7 mRNA nor protein level were affected by flutamide exposure. Both CYP17A1 and 17β-HSD1 were immunolocalized exclusively in small luteal cells, whereas CYP19A1 and 17β-HSD7 were found in large luteal cells of control and flutamide-treated CLs. Overall, flutamide administration led to the alterations in A4, T, and E1, but not in E2, production in the CL of pregnancy in pigs, probably because of disrupted steroidogenic enzymes expression. These changes suggest that androgens are important modulators of luteal function during pregnancy in pigs.

Unfavourable effect of androgen deficiency on aortic stiffness in hypertensive males at low and moderate cardiovascular risk

Unfavourable effect of androgen deficiency on aortic stiffness in hypertensive males at low and moderate cardiovascular risk

In utero exposure to the anti-androgen flutamide influences connexin 43 and β-catenin expression in porcine fetal gonads

Recent reports have indicated a role of cell-to-cell interactions during gonadal development and functions. Numerous reports indicate that fetal hormonal disruption induces abnormalities in the developing reproductive system and, therefore, may interfere with reproductive functions later in adult life. Hence, this study investigated the effect of androgen deficiency during late prenatal periods on the gap junction-associated connexin 43 (Cx43) and the adherens junction-associated β-catenin expression in the fetal porcine gonads. Thus, pregnant gilts were injected with anti-androgen flutamide (for 7 d, 50 mg/kg BW per day) or corn oil (control groups) starting at 83 (GD90) or 101 (GD108) gestational day. On GD90 and GD108 the fetuses were excised and fetal gonads were obtained. To assess Cx43 and β-catenin expression real-time PCR and immunohistochemistry were performed. In fetal testes, Cx43 was localized between Leydig cells, whereas β-catenin was observed mainly within the seminiferous tubules. In fetal ovaries, Cx43 was detected between interstitial cells and between granulosa cells of forming follicles, whereas β-catenin was found within egg nests, in oocytes' membrane, and in granulosa cells of forming follicles. Immunohistochemistry showed decreased Cx43 and β-catenin expression in fetal gonads from flutamide-treated pigs compared with respective controls. However, the ovaries from animals treated with flutamide on GD108 showed increased Cx43 expression. The changes of Cx43 and β-catenin expression after prenatal flutamide treatment were confirmed at the mRNA level. These findings suggest that androgen deficiency during late gestation may lead to disturbed intercellular interactions in fetal porcine testes affecting testicular functions, as well as impaired follicular formation in fetal ovaries. Our results further signify the role of androgens in the regulation of cell-to-cell interactions within fetal porcine gonads.

Age-related androgen deficiency and erectile dysfunction in men of the reproductive age presenting with type 2 diabetes mellitus

Aim of the study. To detect hypogonadism and elucidate its relationship with erectile dysfunction (ED) and the main risk factors of cardiovascular diseases (CVD) among the patients with type 2 diabetes mellitus (DM2). Materials and methods. This clinical epidemiological study included 261 men with DM2 at the age varying from 30 to 59 years. The following exclusion criteria were used: type 1 diabetes mellitus, primary hypogonadism, drug-induced and congenital diseases accompanied by hypogonadism, oncological and cardiovascular diseases. All the patients underwent routine clinical examination, questionnaire and instrumental studies, laboratory analysis including assays for sex hormones. Results. Hypogonadism was diagnosed based on the results of all above studies in 114 (43.7%) men presenting with type 2 diabetes mellitus whereas the AMS questionnaire revealed a 10% higher incidence of age-related hypogonadism (in 141 or 54% subjects). It means that the incidence of hypogonadism increases with age both among the patients with DM2 and in the general male population. For example, only 17.5% of the men at the age of 30-39 years suffered hypogonadism compared with thrice this frequency in the groups of 40-49 and 50-59 year-old subjects. The summarized international erectile function index (IEFI) in the patients with hypogonadism and DM2 was 14.2±0.5 compared with 19.0±0.9 in the group without hypogonadism (p<0.001). Erectile dysfunction was diagnosed in 42 (28.6%) of the 147 patients with DM2 in the absence of hypogonadism whereas all the patients with hypogonadism suffered ED. The groups of the patients presenting with DM2 and hypogonadism and with DM2 without hypogonadism were not significantly different in terms of the number of smokers and hypokinetic subjects (roughly 70%). A similar tendency was documented in the occurrence of such parameters as waist circumference and serum triglycerides levels whereas the total and LDLP cholesterol levels, arterial pressure and body mass index were significantly higher in the patients with hypogonadism. Conclusion. Almost each second man with type 2 diabetes mellitus suffers hypogonadism and the number of such patients increases with age. The presence of DM2 increases the risk of development of ED. Also, the probability of ED and its severity increase under effect of androgen deficiency. The combination of DM2 and hypogonadism promotes manifestation of the main risk factors of cardiovascular diseases.

Physiotherapy interventions for the management of whiplash injuries

Age dependent decrease in androgen levels is the main and most important mechanism responsible for involutional osteoporosis in men. Decreased physical activity may contribute to the development of osteoporosis. Supplementation with DHEA and increased physical activity may counteract the development of male osteoporosis and decrease fracture risk. DHEA may increase bone formation after conversion to testosterone, and exercise — by activation of the canonical Wnt/β-catenin pathway. The aim of the present study was to examine the effect of DHEA and moderate exercise on mechanical properties of long bones in rats with androgen deficiency induced by orchidectomy. The experiments were carried out on 3-month-old Wistar rats, divided into following groups (n=8–10 rats per group): non-orchidectomized control rats, orchidectomized (ORX) control rats, ORX rats receiving DHEA, ORX rats submitted to exercise, ORX rats receiving DHEA submitted to exercise. The rats were submitted to the moderate exercise on the treadmill once daily (1 hour) for 8 weeks. DHEA was administered at a dose 7 mg/kg p.o. once daily for 8 weeks. Mechanical properties of tibial metaphysis and femoral diaphysis (in three-point bending tests) and femoral neck (in a compression test), bone turnover markers (serum osteocalcin and C-terminal telopeptide of type I collagen fragments), geometric parameters, mass, and mass of bone mineral in the tibia and femur were studied. Androgen deficiency inhibited bone formation and resorption. It weakened mechanical properties of tibial metaphysis as well as femoral neck and diaphysis, and decreased bone mass and mass of bone mineral. Exercise increased bone formation and counteracted unfavorable changes in mechanical properties of tibial metaphysis and femoral neck, induced by androgen deficiency. DHEA increased bone formation and significantly inhibited the effect of androgen deficiency on the mechanical properties of the tibial metaphysis. Administration of DHAE combined with exercise counteracted unfavorable changes in bone mechanical properties (especially in the tibial metaphysis) induced by androgen deficiency. This article is part of a Special Issue entitled ECTS 2011. Disclosure of interest: None declared. doi:10.1016/j.bone.2011.03.670 PP540-T Physiotherapy interventions for the management of whiplash injuries V. Barkatsa ⁎, C. Iliadis , V. Moraitis , N. Syrmos , M. Tzagarakis , K. Tsipras d a Physiotherapy, Greece b Neurosurgery, Venizeleion General Hospital, Heraklion, Greece c Pathology, General Hospital, Rethymno, Greece d Endocrinology, Greek Institute of Social Security, Athens, Greece Abstract: Introduction/background: Whiplash injuries are associated with motor Introduction/background: Whiplash injuries are associated with motor vehicle accidents or in sporting mishaps after an acceleration–deceleration mechanism of energy transfer to the neck. The injury results in a series of clinical manifestations (mainly cervical pain 88% and headaches) known as Whiplash Associated Disorder. The syndrome involves trauma to amultiplicity of tissues in the cervical spine and it may affect other areas of the vertebral column. Clinicians are challenged to use different treatments in order to relieve symptoms and to improve body function. Method: systematic review of the effectiveness of physiotherapy interventions in the management of whiplash injuries using MEDLINE, CINAHL, Cochrane database systematic reviews and published guidelines. Results: In the acute stage (0 to 2 weeks after injury) physiotherapy interventions recommended for pain reduction are active exercises, manual mobilisation, use of TENS, education and advice and relaxation techniques compared to electrotherapy, traction, and the use of soft collar. There is insufficient evidence to support the use of massage and acupuncture. In the sub acute stage (2–12 weeks after injury) and in the chronic stage( after 12 weeks) a multimodal programme including active exercises, postural training, manual techniques, physical agents and psychosocial support should be used to reduce pain and enable people to return to normal activities. Conclusion: Recovery is improved by early active management and early return to pre-accidental activities. This article is part of a Special Issue entitled ECTS 2011.

Androgen deficiency: effects on body composition

Published data on the effects of androgen deficiency and testosterone administration on body composition in men and women are reviewed. In experimental paradigms, androgen deprivation decreases lean body mass and increases fat mass in men, and physiologic replacement reverses these abnormalities. The anabolic effects of testosterone administration on muscle in men are well-established, and current understanding of the underlying mechanisms are discussed. Randomized, placebo-controlled studies have been performed to investigate the effects of testosterone administration on body composition in a number of male hypogonadal states, including HIV-associated weight loss, supraphysiologic glucocorticoid administration, aging and obesity, with variable outcomes, and the results are reviewed. There are few data investigating the effects of hypoandrogenemia or androgen replacement on body composition in women, in whom endogenous testosterone levels are a fraction of those in men. A recent randomized, placebo-controlled study of physiologic testosterone replacement therapy in women with profound hypoandrogenemia due to hypopituitarism demonstrated an increase in skeletal muscle mass but no change in body fat. Further research is needed to establish the effects of endogenous androgens on the regulation of body composition in women.

Effects of Androgen Deficiency and Replacement on Prostate Zonal Volumes

No AccessJournal of UrologyUROLOGICAL SURVEY: Benign Prostatic Hyperlasia: Abstracts1 Jul 2002Effects of Androgen Deficiency and Replacement on Prostate Zonal Volumes Steven A. KaplanM.D. Steven A. KaplanSteven A. Kaplan More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)64977-4AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Effects of Androgen Deficiency and Replacement on Prostate Zonal Volumes." The Journal of Urology, 168(1), p. 404 © 2002 by American Urological Association, Inc.FiguresReferencesRelatedDetails Volume 168Issue 1July 2002Page: 404 Advertisement Copyright & Permissions© 2002 by American Urological Association, Inc.MetricsAuthor Information Steven A. Kaplan More articles by this author Expand All Advertisement PDF downloadLoading ...

Effects of Androgen Deficiency and Replacement on Prostate Zonal Volumes

Effects of Androgen Deficiency and Replacement on Prostate Zonal Volumes

Effect of Androgen Deficiency on the Human Meibomian Gland and Ocular Surface

Effect of Androgen Deficiency on the Human Meibomian Gland and Ocular Surface

The influence of sex hormones on vascular responses in the aorta of streptozotocin-diabetic male rats.

Diabetes mellitus reduces gender-related differences in the prevalence of cardiovascular disease by fading the vascular protective effects afforded by estrogen in females. However, the impact of estrogen treatment on and the contribution of androgens to vascular function in vessels from male diabetics are largely unknown. We investigated the effects of androgen deficiency and in vivo estrogen treatment by assessing the responsiveness to a number of vasoactive agents and the formation of eicosanoid mediators in aortic rings from intact and castrated streptozotocin-diabetic rats which had been implanted with 17beta-estradiol (E2) or its vehicle for 5 days. Castration was found to attenuate contractility to noradrenaline, to enhance tone-related release of NO, as shown by curves for N-methyl-L-arginine and superoxide dismutase (SOD), and to increase endothelium-dependent relaxation to carbachol and histamine, compared with intact animals. Smooth muscle sensitivity to exogenous NO and platelet thromboxane A2 production were unchanged but prostacyclin release by aortic tissue dropped by about 40% following castration. Treatment with E2 to intact animals still attenuated contractility to noradrenaline and potentiated relaxation to SOD and histamine but affected no other parameters. In contrast, when E2 was administered to castrated animals, responses to SOD, carbachol and histamine were significantly impaired. Thus, androgen deprivation appears to improve vascular function in male diabetic rats, whereas E2 treatment exerts some beneficial effects in intact, but not in castrated animals. Our findings therefore provide new insights into the role of sex hormones in the development of diabetic vascular complications.

Profound hypogonadism has significant negative effects on calcium balance in males: a calcium kinetic study.

The impact of estrogen deficiency on bone has been extensively studied in the female; however, the effects of androgen deficiency on calcium fluxes in males have been less well characterized. We investigated the effect of short-term, severe androgen deficiency on measures of calcium absorption and kinetics as well as on markers of bone turnover in males. To accomplish this, 11 healthy male volunteers were recruited (mean age 23.3 +/- 0.5 years [SEM], body mass index 25.3 +/- 0.8 kg/m2). They consumed a weight maintenance diet for at least 3 days prior to admission to our Research Unit, with a calcium intake of approximately 1200 mg/day. At baseline (D1), subjects received 42Ca intravenously as well as 44Ca PO mixed with milk or juice. A 29-h urine collection was begun and blood samples collected at frequent intervals for the measurement of the isotopic enrichment of 42Ca and 44Ca using thermal ionization mass spectrometry. Twice daily urine samples were collected for 5 days after the administration of the isotopes. A gonadotropin-releasing hormone agonist (Lupron) was given after D1, again 3 weeks later, and studies repeated identically 4 weeks (D2, n = 6) and 10 weeks from baseline (D3, n = 7) (two subjects completed three studies). Testosterone concentrations were markedly suppressed on both D2 and D3 (-95%, p < 0.006), whereas there were no detectable changes in growth hormone and insulin-like growth factor-1 concentrations. Urinary calcium excretion increased significantly after 4 weeks (43%, p = 0.0007) and 10 weeks (73%, p = 0.003) of sustained hypogonadism. Using a multicompartmental kinetic model, the contribution of oral calcium to the urinary losses was decreased by D3 (-41%, p = 0.01), yet the contribution of bone calcium to urine losses increased by 10 weeks (+11%, p = 0.01). There was a 21% decrease in bone calcium deposition (Vo+) by D3 (p < 0.05) with no significant change in bone resorption rates (Vo-). There was a significant correlation between the decrease in testosterone concentration and the increase in urinary calcium excretion, especially at 10 weeks (R2 = 0.84, p = 0.004). These kinetic changes were accompanied by a decrease in osteocalcin concentrations on D2, with improvements by D3. Urinary N telopeptide, a measure of bone resorption, also increased during the studies. In summary, profound hypogonadism in young males is associated with marked increases in urinary calcium losses, with a greater contribution of bone calcium to those losses and decreased kinetic markers of bone calcium deposition. We conclude that even short-term, severe deficiency in gonadal steroids can have profound negative effects on calcium and bone metabolism in males.

The Effects of Androgen Deficiency on Murine Bone Remodeling and Bone Mineral Density Are Mediated via Cells of the Osteoblastic Lineage

The Effects of Androgen Deficiency on Murine Bone Remodeling and Bone Mineral Density Are Mediated via Cells of the Osteoblastic Lineage

The effects of androgen deficiency on murine bone remodeling and bone mineral density are mediated via cells of the osteoblastic lineage.

Both estrogens and androgens act on bone marrow stromal/osteoblastic cells to inhibit the production of local factors that promote osteoclast development. Based on this and the evidence that loss of sex steroids up-regulates not only osteoclastogenesis but also osteoblastogenesis, we have hypothesized that cells of the osteoblastic lineage are the mediators of the adverse effects of sex steroid deficiency on bone. To test this hypothesis, we used the senescence-accelerated mouse (SAMP6), a model of defective osteoblast development, and examined the effects of orchidectomy on static and dynamic histological features of bone remodeling and on bone mineral density. After orchidectomy in SAMP6 mice, the expected increases in osteoblast precursors, cancellous osteoclasts and osteoblasts, frequency of remodeling events, trabecular spacing, and rate of bone formation were absent or greatly attenuated. Moreover, whereas bone mineral density decreased in orchidectomized controls, it did not change in SAMP6. Our data indicate that when osteoblast development is defective, orchidectomy fails to result in bone loss. This evidence suggests that cells of the osteoblastic lineage are essential mediators of the changes in the rate of bone remodeling and loss of bone mass that ensue following loss of androgens.

Aromatization of androgens is important for skeletal maintenance of aged male rats.

A nonsteroidal aromatase inhibitor vorozole (VOR) was administered to aged (12 months old) male Wistar rats and its effect was compared with the effect of androgen deficiency. The rats were either sham-operated (SHAM) or orchidectomized (ORCH) and treated with or without VOR. Thus, four experimental groups were created (SHAM, ORCH, SHAM + VOR, ORCH + VOR). The follow-up period was 4 months. At the end of the experimental period, bone mineral density (BMD) of the first four lumbar vertebrae and right femur was measured ex vivo with dual-energy X-ray absorptiometry, bone formation was evaluated by serum osteocalcin, and bone resorption by urinary excretion of (deoxy)pyridinoline. Orchidectomy increased bone resorption 2- to 3-fold whereas bone formation was only slightly increased. Treatment of intact male rats with VOR also increased bone resorption (+30% increase) whereas bone formation was not increased in this SHAM + VOR group. Their BMD was 7% lower in the femur (P < 0.01) and 6% lower in the lumbar vertebrae (P < 0.01) compared with the SHAM group that had not received VOR. Moreover, this decrease of bone mineral density was not significantly different from the expected decrease of bone density observed in the ORCH groups (6-10%). This was also reflected by a decrease of calcium content of the first four lumbar vertebrae of 15% (P < 0.001) in the SHAM + VOR group and 9-14% (P < 0.05) in the ORCH groups compared with the SHAM group, respectively. These data therefore suggest that inhibition of aromatization of androgens into estrogens increases bone resorption and bone loss similar to that observed after complete removal of androgens. Aromatization of androgens into estrogens may therefore, at least partly, explain the effects of androgens on skeletal maintenance.

The aged male rat as a model for human osteoporosis: Evaluation by nondestructive measurements and biomechanical testing

Effects of androgen deficiency and androgen replacement on bone density, as measured with dual-energy X-ray absorptiometry (DXA) and single photon absorptiometry (SPA), cortical ratio (cortical thickness/outside bone diameter x 100), and biomechanical properties were evaluated in 14-month-old (1 month after orchiectomy (orch) or sham-operation) and in 17-month-old (4 months after orch or sham) male rats. Whole femoral bone mineral content (BMC) and density (BMD) measured with DXA were not significantly decreased 1 month after orch. Whole femoral BMC and BMD were 10% and 8% lower in 4 months after orch (P < 0.01 and P < 0.001, respectively). This decrease was prevented by testosterone replacement. There was an excellent correlation (R = 0.99) between whole femoral BMC and femoral ash weight. Selective scanning of cortical and cancellous sites of the femur showed that both cancellous and cortical BMC and BMD were significantly decreased 4 months after orch. SPA of the right tibia confirmed a 7% decrease in cancellous BMC and BMD 4 months after orch (preventable by testosterone) but not in cortical BMD and BMC. Femoral cortical ratio decreased with age (47 +/- 2 in 14-month-old and 40 +/- 2 in 17-month-old sham rats versus 63 +/- 1 in 6-month-old male rats) due to a continuously enlarging femoral shaft. Androgen deficiency resulted in an even greater decrease of the cortical ratio 4 months after orch (36 +/- 2 in 17-month-old orch rats) that was again prevented by testosterone (47 +/- 3).(ABSTRACT TRUNCATED AT 250 WORDS)