Estrogen deficiency in men is a challenge for both the hypothalamus and pituitary.
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Biomedical subjects
Publications and source records attributed to D Vanderschueren.
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Both a decrease in bone formation and an increase in bone resorption have been implicated in the pathogenesis of age-related (type II) femoral neck osteoporosis. While the increase in the bone resorption rate has been shown to be partially related to secondary hyperparathyroidism, the mechanisms underlying the decline in bone formation have not yet been identified. The aim of the present study was to test the hypothesis that the bone formation deficit associated with type II osteoporosis might be due to secondary hyperparathyroidism and/or to a deficiency of the insulin-like growth factor (IGF) system. Circulating concentrations of IGF-I, IGF-II, IGF binding protein (IGFBP)-3, IGFBP-4, IGFBP-5, 25-hydroxycholecalciferol (25(OH)D3), and intact parathyroid hormone (PTH) were measured in 50 elderly women after sustaining a hip fracture and in 50 healthy age-matched controls. In addition, serum levels of osteocalcin (OC), skeletal alkaline phosphatase, and N-terminal procollagen peptide and urinary pyridinium cross-links were determined as markers of bone remodeling, and bone mineral density (BMD) was assessed at the proximal femur. In the patient group, serum was drawn within 18 h of the fracture and prior to surgery. Circulating protein concentrations did not change over this time frame. No difference was found between mean IGFBP-4 serum levels in the two groups studied, while mean levels of IGF-I, IGF-II, IGFBP-3, IGFBP-5, 25(OH)D3, and markers of bone formation were significantly lower (p < 0.006) in patients as compared with healthy subjects. Serum PTH and urinary pyridinium cross-links, however, were markedly increased (p < 0.001) in the osteoporotic group. In pooled data from the normal and osteoporotic populations, age-adjusted multiple regression models based on IGF-I, IGF-II, IGFBP-3, and IGFBP-5 were found to be highly predictive of serum OC (R2 = 19%, p < 0.001) and BMD of femoral neck (R2 = 49%, p < 0.0001), consistent with an effect of the anabolic IGF components on overall bone formation rate. Similar models based on 25(OH)D3 and PTH, however, were statistically unrelated to OC. To address further the potential impact of trauma on circulating IGF system components, we measured IGF system component levels in 10 male patients within 18 h following tibial fracture and in 10 age-matched normal male subjects. There was no significant difference in serum level of any of the IGF system components between the two groups. Although limited by its cross-sectional design, the present study suggests that, in addition to bone resorption resulting from secondary hyperparathyroidism, impaired bone formation associated with deficiency of the IGF system might predispose elderly women to fragility fracture of the proximal femur.
In the lay press, a worldwide decline in male fertility is often accepted. In fact, this assumption is based on a meta-analysis of "normal sperm parameters" in the medical literature between 1938-1998 and based on retrospective studies from several centers. Other studies, however, have not shown a decrease of sperm parameters. Some have even shown an increase of sperm parameters. Some have even shown an increase of sperm parameters. A critical analysis of all these studies shows great differences between studies in selection of normal men, measurement of sperm parameters, analysis of data, ... Also, unexplained geographical differences in sperm density exist that may influence the analysis. In conclusion, a worldwide decline of sperm quality or male fertility has not been scientifically proved.
Diabetes mellitus may cause debilitating somatic complications and a high psychosocial burden. Impaired sexual function (erectile dysfunction) is a well-established complication in men. Does diabetes also have an effect on sexuality of women? Since the first publication in 1971, only 15 studies in this area have been published and their results are contradictory. The purpose of this article is to offer a review of these results. As a conclusion, a new hypothesis on the specific influence of diabetes on female sexuality and suggestions for further research are formulated.
OBJECTIVE: To test the hypothesis that alpha-glycosidase activity in seminal plasma can predict the outcome of both IUI and IVF. DESIGN: A retrospective cohort study. SETTING: Tertiary fertility center in a university hospital. PATIENT(S): Eighty-three subfertile couples who underwent IUI and 125 subfertile couples who underwent IVF. INTERVENTION: None. MAIN OUTCOME MEASURE(S): Determination of the alpha-glycosidase activity in seminal plasma before an IUI or IVF attempt, correlation of alpha-glycosidase activity and other semen parameters, and prediction of pregnancy using alpha-glycosidase activity in seminal plasma. RESULT(S): Alpha-glycosidase activity correlated with sperm count. In the IUI group, alpha-glycosidase activity of >23.9 mU/mL predicted pregnancy with a sensitivity of 100% and a specificity of 55.2%. In the IVF group, the outcome could not be predicted with use of any of the semen parameters. CONCLUSION(S): Alpha-glycosidase activity measured in mU/mL probably can be used as a predictor for IVF and pregnancy in an IUI program but has no predictive value with regard to pregnancy rate in an IVF program.
The development of assisted reproductive technologies, such as intracytoplasmic sperm injection (ICSI) substantially improved the outlook for patients with severe male fertility problems. However this implies that for the first time genetic defects associated with male in- or subfertility might be transmitted to offspring and result in genetic disease [de Kretser DM, The potential of intracytoplasmic sperm injection (ICSI) to transmit genetic defects causing male infertility. Reprod. Fertil. Dev. 1995;7:137-142]. The knowledge of male specific fertility genes on the Y chromosome increased enormously in the last decade. The SRY gene plays a critical role in gonadal differentiation. DAZ, SPGY and related genes on the Y chromosome are very important for spermatogenesis. Interstitial Y-chromosomal microdeletions encompassing the AZFa, b or c region have become an additional class of genetic abnormalities causing male infertility. A review is given of the different genetic aspects of male infertility.
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Serum parathyroid hormone, calcium and phosphate were daily monitored in 12, 30 and 30 patients respectively during the early postoperative period after removal of a solitary parathyroid adenoma. In all patients PTH concentration dropped to very low values on the first postoperative day, whereafter a rapid recovery began. So the first day is the best time to evaluate the results of the intervention. Hypocalcemia was most frequent on the third day. After ten days 26 patients showed a normal calcemia, while 4 patients still had a mild hypocalcemia (8-8.8 mg/dl). These data may guide management of patients after parathyroid surgery.
This case report describes a couple suffering from infertility secondary to psychogenic anejaculation, which was refractory to all conservative treatment modalities. A first trial of microsurgical vas aspiration in combination with in-vitro fertilization (IVF) resulted in a pregnancy. After 2 years, three more trials of microsurgical vas aspiration in combination with either IVF or subzonal insemination (SUZI) resulted in embryo transfer without pregnancy. Finally, after 3 years, spermatozoa obtained by rectal probe stimulation under general anaesthesia were cryopreserved. A second intracytoplasmic sperm injection (ICSI) procedure using these cryopreserved spermatozoa also resulted in a second pregnancy. Although sperm concentration was in the normal range, in all samples obtained by either rectal probe electrostimulation or microsurgical vas aspiration, motility was <30% in all but two samples.
The aim of this experiment was to design a suitable mouse model for male subfertility in which to study the effect of decreased sperm quality on embryo quality in vivo and in vitro. To achieve male subfertility, testes of adult male mice were immersed in water at either 42 degrees C (heated) or 33 degrees C (controls) during 20 min. Twenty-eight days after treatment, all heat stressed males showed a significant decrease in relative testis weight [384.7 mg in controls (286.7-460.6) versus 323 mg in stress heated groups (117.9-405.6); P < 0.001], sperm concentration [3.75 x 10(6)/ml (2.75-7.25) versus 1.00 x 10(6)/ml (0-4.00); P < 0.001] and progressive sperm motility [57.5% (48.0-79.0) versus 42.5% (14.0-66.0); P < 0.001]. Moreover, after mating to heat exposed males, not only the number of pregnant females (20/22 versus 18/30) but also the weight of their embryos [275.4 mg (78.7-339.4) versus 261.8 mg (68.1-339.0); P < 0.001] was significantly lower at 14.5 days post coitum when compared to controls. Neither the number of resorption sites nor the number of viable embryos per pregnant female was significantly different between groups. Also, the in-vitro fertilization rate of oocytes, fertilized by spermatozoa collected from heat stressed males, was significantly lower (44.9%; P < 0.0001) when compared to controls (65.1%; P < 0.0001). In conclusion, the results of this study suggest that male subfertility induced by acute scrotal heating may result in impaired sperm quality, reduced embryo weight in vivo and decreased fertilization rate in vitro.
Osteoporotic fractures, and especially hip fractures, are a leading cause of morbidity and mortality among elderly men. Among other factors, a decline in bone mass has been identified as the major determinant of the age-related reduction in bone strength and therefore of osteoporotic fracture risk. Recent evidence suggests that age-associated endocrine deficiencies may contribute to femoral bone loss and hip fracture occurrence in elderly men. The decline in circulating androgen levels and the decreased activity of the growth hormone insulin-like growth factor-I axis may result in a reduction in bone formation that contributes to the age-related increase in bone fragility in men. Vitamin D deficiency-induced secondary hyperparathyroidism, on the other band, may further enhance bone loss by activating bone turnover and so increasing the number of bone remodelling units with impaired bone formation. On the basis of these pathophysiological models, guidelines can be developed for the prevention of age-related bone loss in men, but these approaches lack validation. The results of controlled intervention trials will have to be awaited to answer the question of whether hormone replacement therapy attenuates bone loss and reduces fracture incidence in elderly men.
Male subfertility often remains unexplained. Severe intrauterine growth retardation has previously been linked to hypergonadotropic hypogonadism. We examined whether reduced fetal growth, as judged by low birth weight, is associated with unexplained male subfertility later in life. Birth weight and gestational age were obtained by questionnaire from male partners of couples consulting for subfertility, and were transformed into birth weight SD scores. Men with normal semen analysis (n = 128) had a median birth weight SD score of 0.0 (P25-P75 range: -0.7 to 1.0), comparable to that of men with explained subfertility (n = 28), and higher (p = 0.012) than that of men with unexplained subfertility (n = 32; median -0.5 SD score; P25-P75 range: -0.9 to -0.1). These results extend the link between reduced fetal growth and male subfertility to a range of birth weight that is well within normality. The pathophysiologic mechanism governing this association now remains to be unraveled.
Aromatization of androgens into estrogens may explain some of the skeletal action of androgens. We examined the effect of the aromatase inhibitor Vorozole (VOR) on skeletal growth and mineral accumulation in growing 6-week-old male Wistar rats. Rats were either Sham-operated (Sham) or Orchidectomized (Orch) and treated with or without the aromatase inhibitor VOR. One Sham-operated group was killed at Baseline (Base); the four other groups (Sham, Sham + VOR, Orch, Orch + VOR) were killed 18 weeks after surgery. As expected, all groups gained body weight, but body weight gain was significantly (-25%) lower in Orch, Orch + VOR, and Sham + VOR. Both bone formation, as assessed by serum osteocalcin, and bone resorption, as assessed by urinary (deoxy)pyridinoline, decreased significantly in all groups compared with Base. Orchidectomy resulted in a relative increase of biochemical markers of bone formation and resorption compared with Sham. Treatment with VOR, however, resulted only in a very moderate increase of (deoxy)pyridinoline compared with Sham. As expected, femoral length increased compared with Base, but orchidectomy reduced the relative growth of the femur whereas VOR did not influence femoral length. Ex vivo, densitometric and geometric properties of the femora were evaluated by peripheral computerized quantitative tomography (pQCT) and dual-energy x-ray absorptiometry (DXA). The lumbar vertebrae were measured by DXA. At the end of the experimental period, volumetric trabecular bone mineral density (vTBMD) measured at the distal end of the femur was significantly lower not only in both Orch groups but also in Sham + VOR. The decrease of cancellous bone density in Sham + VOR was lower than in the orchidectomized animals. A relative decrease of femoral inner and outer diameters compared with Sham and Base was observed in both Orch groups and in Sham + VOR, suggesting that both orchidectomy and VOR-treatment inhibited periosteal bone formation and endosteal bone resorption. Only orchidectomy, however, resulted in a decrease of cortical thickness. Bone area, mineral content, and density of both femora and lumbar vertebrae, measured by DXA, were decreased to a similar extent by VOR and Orch (bone mineral content of the femur was 467 +/- 18 mg in Orch and 461 +/- 10 mg in Sham +/- VOR vs. 521 +/- 11 mg in Sham; P < 0.001). In conclusion, treatment with the aromatase inhibitor VOR impairs body weight gain and skeletal modeling and decreases bone mineral density. Aromatase inhibition had similar final effects on bone mass and size as castration, but with less marked effects on bone turnover.
The problem of osteoporosis in men has recently been recognized as an important public health issue. To test the hypothesis that endocrine deficiency-mediated alterations in bone metabolism might contribute to osteoporotic fracture risk in elderly men, serum levels of 25-hydroxycholecalciferol (25(OH)D), 1,25-dihydroxycholecalciferol (1,25(OH)2D), intact parathyroid hormone (PTH), testosterone, and estradiol were measured in 40 males (mean age 73 years) who were consecutively recruited within 18 h following a fracture of the proximal femur, and in an equal number of community-living older men (mean age 72 years) who served as controls. In addition, circulating osteocalcin and urinary excretion of (deoxy)pyridinoline were determined as markers of bone formation and resorption, respectively. No differences were observed between the mean serum concentrations of osteocalcin and estradiol. Serum levels of 25(OH)D, 1,25(OH)2D, and testosterone, however, were decreased in hip fracture patients. When correcting for differences in vitamin D binding protein, differences in 1,25(OH)2D did not persist, whereas serum 25(OH)D was still significantly lower in patients than in controls (6.1 +/- 4.3 vs. 7.6 +/- 2.8, p = 0.01). Similarly, a highly significant deficit was observed in the free testosterone index, calculated from total testosterone and the level of sex hormone binding globulin (2.6 +/- 1.3 vs. 8.2 +/- 2.9, p < 0.001). Serum PTH and urinary pyridinium cross-links, however, were markedly increased in the fracture group. Moreover, in fracture patients, free 25(OH)D and free testosterone were both significant and mutually independent negative predictors of (deoxy)pyridinoline excretion. Although limited by its cross-sectional design, the present study suggests that both hypovitaminosis D and androgen deficiency may predispose to bone resorption in elderly men and in turn to remodeling imbalance and fracture risk.
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.
Androgens are needed during the entire lifespan of the male skeleton -at least in the rat. Indeed, in aged nongrowing male rats, androgens are necessary for the maintenance of skeletal integrity. In these animals, androgen deficiency results in a menopause-like acceleration of bone turnover and bone loss which are presented by androgen replacement. In the growing skeleton, androgens probably have a twofold effect. Not only neonatal androgens but also pubertal androgen secretions are needed for normal skeletal growth and modeling in order to reach full size (cortical) bone mass. Moreover, androgens are not only necessary for the (cortical) bone mass but also for the maintenance of cancellous bone compartment during growth, at least in androgen-deficient rats. However, both animal experiments and recent human data suggest that at least part of the complex skeletal effects of androgens may depend on the aromatization of androgens into estrogens.