Testosterone Deficiency and Bone Metabolism Damage in Testicular Cancer Survivors.

The aim of the study was to investigate the influence of therapeutic modalities and sexual hormone levels on changes in bone mineral density (BMD) in testicular cancer (TC) survivors. In a cross-sectional descriptive, long-term follow-up study, a total of 1,249 long-term TC survivors were evaluated according to treatment modality: orchiectomy (OE) only, OE + chemotherapy (CT), or OE + radiotherapy (RT). Luteinizing hormone (LH), total testosterone (TST), marker of bone resorption (ß-carboxyl-terminal cross-linking telopeptide of type I collagen-CTx), and BMD were evaluated. Standard statistical techniques were used to test the differences between groups of patients. TST decrease was observed in 46/313 TC survivors after OE alone, in 103/665 after OE + CT, and in 66/271 after OE + RT. LH increase was observed in 23/313 TC survivors after OE alone, in 154/665 after OE + CT, and in 43/271 after OE + RT. CTx increase was observed in 116/313 TC survivors after OE alone, in 324/665 after OE + CT, and in 82/271 after OE + RT. Osteopenia/osteoporosis occurred in 136/313 TC survivors after OE alone, in 298/665 after OE + CT, and in 139/271 after OE + RT. TC survivors after RT have statistically significant decreased TST levels, increased LH and nonsignificant worse BMD (osteopenia/osteoporosis) in comparison with TC survivors after OE alone or CT. TST decrease and LH increase were statistically significant, more frequently observed in patients with osteopenia/osteoporosis. Examination of TST is an important part of follow-up in TC survivors with bilateral as well as unilateral disease. The important part of standard examination algorithm should be also the osteological examination of TC survivors mainly in patients with androgen deficiency.

Biochemical and histopathological effects on the rat testis after exposure to electromagnetic field during fetal period / Efectos bioquímicos e histopatológicos en el testículo murino después de la exposición a campos electromagnéticos durante el periodo fetal

OBJECTIVES: Electromagnetic radiation (ER) emitted from cell phones may exert a detrimental influence on human health and may affect the man reproductive system. We aimed to study the biological and morphological effects on the testes of 60-day-old male rats after ER exposure (900 MHz), which was applied continuously throughout embryogenesis. METHODS: A total of six pregnant Sprague Dawley rats were included in the study. Three pregnant rats (experimental group) were exposed to radiation from a cell phone set to talking mode for 24 hours a day for 20 days, and the other 3 pregnant rats (control group) were not to exposed to radiation. Newborn male rats were included from the experimental group (n=7) and the control group (n=7). At the end of 60 days, the rats' testes were excised, and testis length, width, depth, and weight were measured. Histopathological examinations were compared and serum testosterone (T) levels were assayed biochemically. RESULTS: : While serum T level (3.51±0.21 ng/ml) of ER Exposed group was significantly lower than the control group (4.04±0.47 ng/ml, p = 0.018), Caspase-3 enzyme activity (2.00±0.88) was significantly higher than the control group control (1.00±0.63, p = 0.026). Johnsen score (8.4±0.5) of ER group was fairly lower than the control group (9.4±0.5, p= 0.010). CONCLUSION: Our study demonstrated that ER exposure throughout embryogenesis may cause reductions in serum total T levels and in the size and weight of the testes of male rats, while causing modest increase in apoptosis

OBJETIVOS: La radiación electromagné- tica (RE) emitida por los teléfonos móviles puede tener una influencia deletérea sobre la salud en humanos y puede afectar al sistema reproductor masculino. Buscamos estudiar los efectos biológicos y morfológicos en los testículo de ratas macho de 60 días de edad después de la exposición continua a RE (900 MHz) aplicada continuamente durante el periodo embrionario. MÉTODOS: En el estudio se incluyeron un total de seis ratas Sprague Dawley embarazadas. Tres ratas embarazadas (Grupo experimental) fueron expuestas a la radiación de un teléfono móvil en modo conversación las 24 horas diarias durante 20 días, y las otras tres (grupo control) no fueron expuestas a radiación. Fueron incluidas las ratas macho nacidas del grupo experimental (n=7) y del grupo control (n=7). Al final de los 60 días se extirparon los testículos de las ratas y se midieron la longitud, anchura, profundidad y peso testiculares. Se compararon las valoraciones histopatológicas y se detectaron bioquímicamente los niveles de testosterona sérica. RESULTADOS: Mientras que los niveles de testosterona sérica del grupo expuesto a RE (3,51±0,21ng/ml) eran significativamente menores que los del grupo control (4,04±0,47 ng/ml, p = 0,018), la actividad de la enzima Caspasa 3 era significativamente superior a la del grupo control (1,00±0,63, p = 0,026). El score de Johnsen del grupo de RE (8,4±0,5) fue bastante más bajo que el del grupo control (9,4±0,5, p= 0,010). CONCLUSIONS: Nuestro estudio demostró que la exposición a RE durante la embriogénesis puede provocar reducción de los niveles séricos de Testosterona total y del tamaño y peso de los testículos de las ratas macho, causando a la vez un aumento modesto de la apoptosis

Testosterone and body composition in men after treatment for rectal cancer.

INTRODUCTION: Preoperative radiotherapy for rectal cancer may affect Leydig cell function. However, the diagnosis of posttreatment hypogonadism is complicated as sexual symptoms associated to hypogonadism can rely on adverse events of pelvic radiation and surgery. AIM: The objective of this study was to investigate the association of testosterone levels and body composition. The clinical value of such an association is tested subsequently in the study population. METHODS: This was a longitudinal study with prospective registration during 2010-2012 and 1-year follow up. Men with rectal cancer stage I-III, treated with radiotherapy and surgery, were eligible, and 40 of 53 men were available for analysis. MAIN OUTCOME MEASURES: The areas of skeletal muscle and adipose tissue were assessed on a defined section of a computed tomography at baseline and after 1 year. Androgen levels were recorded from morning blood samples. RESULTS: The area of skeletal muscle was related to the level of bioavailable testosterone (P = 0.01) but not to the level of serum testosterone (P = 0.36). The subcutaneous adipose tissue was not related to testosterone levels. Men with posttreatment serum testosterone levels of 8-12 nmol/L and longitudinal loss of psoas muscle area had a significantly increased luteinizing hormone-testosterone ratio compared with those with longitudinal gain of psoas muscle. CONCLUSIONS: The area of psoas muscle is related to the unbound fraction of circulating testosterone in men treated for rectal cancer. The longitudinal loss of psoas muscle in men with borderline levels of serum testosterone seems to be an androgen-related symptom associated with compensatory activation of the pituitary-gonadal axis indicating a testicular failure in this group of patients.

Rat models of post-irradiation recovery of spermatogenesis: interstrain differences.

Recently, we reported large differences between rat strains in spermatogenesis recovery at 10 weeks after 5-Gy irradiation suggesting that there are interstrain as well as interspecies differences in testicular radiation response. To determine whether these interstrain differences in sensitivity might be a result of the particular dose and time-point chosen, we performed dose-response and time-course studies on sensitive Brown-Norway (BN) and more resistant spontaneously hypertensive rats (SHR) and Sprague-Dawley (SD) rats. Type A spermatogonia were observed in atrophic tubules at 10 weeks after irradiation in all strains indicating that tubular atrophy was caused by a block in their differentiation, but the doses to produce the block ranged from 4.0 Gy in BN to 10 Gy in SD rats. Although the numbers of type A spermatogonial were unaffected at doses below 6 Gy, higher doses reduced their number, indicating that stem cell killing also contributed to the failure of recovery. After 10 weeks, there was no further recovery and even a decline in spermatogonial differentiation in BN rats, but in SHR rats, sperm production returned to control levels by 20 weeks after 5.0 Gy and, after 7.5 Gy, differentiation resumed in 60% of tubules by 30 weeks. Suppression of testosterone and gonadotropins after irradiation restored production of differentiated cells in nearly all tubules in BN rats and in all tubules in SHR rats. Thus, the differences in recovery of spermatogenesis between strains were a result of both quantitative differences in their sensitivities to a radiation-induced, hormone-dependent block of spermatogonial differentiation and qualitative interstrain differences in the progression of post-irradiation recovery. The progression of recovery in SHR rats was similar to the prolonged delays in recovery of human spermatogenesis after cytotoxic agent exposure and thus may be a system for investigating a phenomenon also observed in men.

The effect of progesterone on the electron emission and degradation of testosterone.

Based on recent findings that hormones can emit electrons () from their excited singlet state in polar media, it was of importance to study a possible mutual interaction of progesterone (PRG) and testosterone (TES) in this respect. Hormones of highest purity were dissolved in an air-free mixture of 40% triply distilled water and 60% ethanol, because the hormones are unsoluble in water. As energy source for substrate excitation in singlet state served a monochromatic UV-light (254 nm), the emitted electrons were scavenged by chloroethanol, whereby the quantum yield of produced Cl⁻ ions, Q (Cl⁻), is equal to Q(e⁻(aq)). Hormone degradation initiated by the electron emission was studied by HPLC method, using a Zorbax Eclipse XDB-C18 column (150 mm x 4.6 mm, 5 µm). The quantum yield of emitted e⁻(aq), Q(e⁻(aq)), from TES was 3.6 times higher than that from PRG, which is explained by the different molecular structures of the hormones. Observed 2nd and 3rd maxima of electron emission indicate the ability of TES and PRG products to also eject e⁻(aq), but with lower yield. It can be stated that a part of the emitted electrons from TES are consumed by PRG⁺ leading to a partial regeneration of hormone. The present results offer a deeper insight in the biological behavior of hormones.

Light induced degradation of testosterone in waters.

The degradation of testosterone under simulated irradiations was studied in phosphate buffers and in natural waters at various excitation wavelengths. The quantum yield of photolysis was significantly lower at 313 nm (2.4 x 10(-3)) than at 254 nm (0.225). The formation of several photoproducts was observed, some of them being rapidly transformed in turn while others show higher stability towards subsequent irradiations. The nature of the main products was tentatively identified, both deduced from their spectral and spectrometric data and by comparison with synthesised standard compounds. Among the obtained photoproducts, the main one is possibly a spiro-compound, hydroxylated derivative of testosterone originating from the photohydratation of the enone group. The photodegradation pathway includes also photorearrangements. One of them leads to (1,5,10)-cyclopropyl-17beta-hydroxyandrostane-2-one. The pH of the water does not seem to affect the rate of phototransformation and the nature of the by-products.

Electron emission from photo-excited testosterone in water-ethanol solution.

Testosterone (TES; 4-androstene-17beta-ol-3-on) is found for the first time to eject electrons from its singlet excited state in water-ethanol solvent mixture. This ability was very recently also observed for 17beta-estradiol (17betaE2) and progesterone (PRG)/1/. With increasing TES-concentration, the yield of solvated electrons (e(s)(-)) is decreasing, because of "associate" formation. At higher absorbed UV-doses (lambda=254 nm) the e(s)(-) yield is passing a sharp maximum by formation of TES-ethanol adducts, which are able likewise to emit electrons when excited. At prolonged irradiation the resulting photolytic products of TES-ethanol adducts are also able to emit electrons. The capability of the hormones: 17betaE2, PRG and TES to eject electrons and the resulting metabolites, some of which can induce cancer, is discussed.

A systematic review of the gonadal effects of therapeutic radioactive iodine in male thyroid cancer survivors.

BACKGROUND: For patients with well-differentiated thyroid carcinoma (WDTC), the gonadal effects of radioactive iodine (RAI) therapy is an important consideration. OBJECTIVE AND METHODS: We systematically reviewed the controlled studies examining the gonadal effects of RAI therapy in male WDTC survivors. We searched in nine electronic databases. All abstracts and papers were independently reviewed by two reviewers. RESULTS: After reviewing 334 abstracts and 59 full-text papers, seven papers were included. In longitudinal studies examining the effect of single primary RAI dose activities of 594 mCi. Cumulative RAI dose correlated with FSH measurements at long-term follow-up. In one study, approximately one in eight men experienced oligospermia 1 year after RAI therapy. Rates of infertility, pregnancy loss and offspring congenital malformation were not elevated, but studies were limited by small size and self-reported outcomes. CONCLUSIONS: Abnormalities in testicular function are common within several months of a single therapeutic dose of RAI for WDTC. Biochemical abnormalities usually resolve within 18 months after administration of a single activity of < 150 mCi of RAI. The risk of persistent gonadal dysfunction is increased after repeated or high cumulative RAI activities. Controlled, prospective studies, with long-term follow-up, examining male gonadal and offspring effects of RAI therapy are needed.

Testicular dose in prostate cancer radiotherapy: impact on impairment of fertility and hormonal function.

PURPOSE: To determine the dose received by the unshielded testicles during a course of 20-MV conventional external-beam radiotherapy for patients with localized prostate cancer. Critical evaluation of the potential impact on fertility and hormonal impairment in these patients according to the literature. PATIENTS AND METHODS: The absolute dose received by the testicles of 20 randomly selected patients undergoing radiotherapy of prostate cancer was measured by on-line thermoluminescence dosimetry. Patients were treated in supine position with an immobilization cushion under their knees. A flexible tube, containing three calibrated thermoluminescence dosimeters (TLDs) was placed on top or underneath the testicle closest to the perineal region with a day-to-day alternation. The single dose to the planning target volume was 1.8 Gy. Ten subsequent testicle measurements were performed on each patient. The individual TLDs were then read out and the total absorbed dose was calculated. RESULTS: The mean total dose (+/- standard deviation) measured in a series of 10 subsequent treatment days in all patients was 49 cGy (+/- 36 cGy). The calculated projected doses made on a standard series of 40 fractions of external-beam radiotherapy were 196 cGy (+/- 145 cGy). The results of this study are appraised with the available data in the literature. CONCLUSION: The dose received by the unshielded testes can be assessed as a risk for permanent infertility and impairment of hormonal function in prostate cancer patients treated with external-beam radiotherapy.

The influence of chronic exposure to low frequency pulsating magnetic fields on concentrations of FSH, LH, prolactin, testosterone and estradiol in men with back pain.

OBJECTIVES: There is widespread public concern that electromagnetic fields might be hazardous. However, studies on the biological effects of magnetic fields (MFs) have not always been consistent. Influence of extremely-low frequency MFs used in physiotherapy on endocrine system was rarely examined. Therefore, the aim of the present study was to investigate the concentrations of some pituitary (FSH, LH, prolactin) and sex (testosterone, estradiol) hormones in men with back pain exposed to magnetic fields applied during magnetotherapy or magnetostimulation over the period of three weeks. MATERIAL AND METHODS: The study was performed on 20 men aged 28-62 years (mean+/-SEM: 46.4+/-2.0 years) suffering from chronic low back pain who underwent magnetotherapy (10 patients, mean age+/-SEM: 48.4 years, range: 28-62 years) or subjected to magnetostimulation (10 patients, mean age+/-SEM: 44.3 years, range: 34-52 years) for 15 days (daily at 10:00 h, with weekend breaks). Blood samples were collected at 08:00 before magnetic field application, one day and one month following the application. Concentrations of hormones were measured by micromethod of chemiluminescence. RESULTS: Both magnetotherapy and magnetostimulation lowered levels of prolactin. The levels of LH decreased significantly one month after magnetotherapy in comparison with the baseline whereas following magnetostimulation slight but insignificant increase was observed. Estradiol concentrations were significantly lower one day and one month following magnetosimulation in comparison to the baseline and did not change after magnetotherapy. No statistically significant changes were observed in levels of FSH and testosterone after either magnetotherapy or magnetosimulation at any time examined. CONCLUSION: Magnetic fields applied in physiotherapy exert no or very subtle effect on concentrations of FSH, LH, prolactin, testosterone, and estradiol in men.

Radiation therapy induced changes in male sex hormone levels in rectal cancer patients.

BACKGROUND AND PURPOSE: To determine the effect of curative radiation therapy (46-50 Gy) on the sex hormone levels in male rectal cancer patients. MATERIALS AND METHODS: Twenty-five male rectal cancer patients (mean age 65 years), receiving pelvic radiation therapy (2 Gyx23-25 fractions in 5 weeks) were included. Serum testosterone, FSH and LH were determined before start of treatment, at the 10th and 25th fractions, and 4-6 weeks after completed radiotherapy. The testicular dose was determined by thermoluminescent dosimetry. RESULTS: Five weeks of radiation therapy (46-50 Gy) resulted in a 100% increase in serum FSH, a 70% increase in LH, and a 25% reduction in testosterone levels. After treatment, 35% of the patients had serum testosterone levels below lower limit of reference. The mean radiation dose to the testicles was 8.4 Gy. A reduction in testosterone values was observed already after a mean dose of 3.3 Gy (10th fraction). CONCLUSION: Radiation therapy (46-50 Gy) for rectal cancer resulted in a significant increase in serum FSH and LH and a significant decrease in testosterone levels, indicating that sex hormone production is sensitive to radiation exposure in patients with a mean age of 65 years.

Preparation of biodegradable microspheres of testosterone with poly(D,L-lactide-co-glycolide) and test of drug release in vitro.

Biodegradable microspheres formulation of testosterone (T) can be used as a new physiological approach for androgen replacement in hypogonadal men. In this study, poly(D,L-lactide-co-glycolide) (PLGA) microspheres containing T were prepared by a solvent-evaporation/solvent-diffusion process and the drug release tests of the microspheres were carried out in vitro. T/PLGA microspheres with good yield, desired size and satisfied drug loading were obtained. A significant testosterone sustained release was shown in the drug release tests in vitro. Since PLGA microspheres preparations are normally sterilized by colbat-60 irradiation, the effects of 25 kGy colbat-60 irradiation on physicochemical properties and in vitro drug release profile of T/PLGA microsphere were investigated. The results showed that the irradiation didn't have any effects on the physicochemical properties of T. Though about one-third decrease in molecular weight of PLGA was caused by the irradiation, no significant changes were observed on the drug release profile in vitro.

Endocrine and reproductive health status of men who had experienced short-term radiation exposure at Chernobyl.

Hormonal and semen parameters in 416 men aged 25-45 years were examined: 328 were men who cleaned the territory around the Chernobyl nuclear reactor (called 'liquidators') and 88 were healthy age-matched controls. The dose of radiation received by the liquidators was 0.16 +/- 0.08 Gy. LH, FSH, prolactin, testosterone and cortisol levels were assayed using WHO-matched reagents. Semen analyses were performed according to the WHO Manual (1992). The mean concentration of all hormones in liquidators and controls were within the WHO-defined normal range. The mean levels of LH and cortisol in liquidators were significantly lower (p = 0.013 and p < 0.001, respectively) and testosterone significantly higher (p = 0.023) than in controls. The variations in hormone levels in liquidators were not correlated with the acquired doses of radiation as measured by personal dosimeters (film badges). Semen parameters in a subgroup of 70 liquidators were within the normal WHO-defined range. The percentage of normal forms of spermatozoa in liquidators (35.0 +/- 13.1%) was significantly lower (p < 0.015) than in a control group (42.8 +/- 8.9%). The study has shown that exposure of men to relatively short-term radiation did not cause long-lasting disruption of their endocrine status and spermatogenesis. The study was 7-9 years retrospective and it is therefore impossible to infer what the immediate effects of the radiation exposure were on these parameters.

[The early and late reactions of the thyroid-gonadal link in rats of different age groups to the action of ionizing radiation]. / Rannie i otdalennye reaktsii tireoid-gonadnogo zvena krys raznykh vozrastnykh grupp na vozdeistvie ioniziruiushchego izlucheniia.

Pubertal and prepubertal rats were exposed to single (at doses of 0.1, 1, 10 Gy) or fractionated (at total doses of 1 and 10 Gy) X-ray irradiation. It has been shown that the irradiation is accompanied by the one-way phasic changes of thyroid and genital glands independently of the animals' puberty. Remote oppression of activity of the studied glands is the distinctive feature of these changes.

ENDOR study of gamma-irradiated hydrated testosterone orthorhombic single crystals.

The molecular structure of free radicals formed in gamma-irradiated orthorhombic single crystals of hydrated testosterone was investigated by Electron Nuclear Double Resonance (ENDOR) spectroscopy. Only one kind of radical was observed, which is formed by addition of hydrogen atom to oxygen atom O(3). We observed interaction of the unpaired electron, which is delocalized on the carbons C(3), C(4) and C(5), with one alpha-proton in position 4 and with four unequivalent beta-protons connected with the carbon atoms C(2) and C(6). The matrices of the hyperfine couplings and the g-factor of the radical are given.

[Corticosterone and testosterone in the blood of adult rats: the effects of low doses and the times of the action of ionizing radiation during intrauterine development]. / Kortikosteron i testosteron v krovi vzroslykh krys: éffekty nizkikh doz i sroka deistviia ioniziruiushchei radiatsii v period vnutriutrobnogo razvitiia.

Corticosterone levels in the blood and adrenal weights in adult rat males were increased after low-dose gamma irradiation during the last third of their intrauterine development; an increase of the dose decreased them. Decrease in testosterone levels and testis weights were dose-dependent. External and internal irradiation of females on the 11-14 days of pregnancy inhibited adrenals and increased testosterone levels and seminal vesicles weights in offspring. The changes of hormonal balance in adult animals depend on dose and period of ionizing irradiation during intrauterine development.

[Experimental research on the biological action of the pulse-modulated microwave radiation created by shipboard radar stations]. / Eksperimental'noe issledovanie biologicheskogo deistviia impul'snomodulirovannykh mikrovolnovykh izluchenii, sozdavaemykh sudovymi radiolokatsionnymi stantsiiami.

The article represents experimental data on influence of impulse modulated microwave irradiation with discontinuous effects varying in intensity and exposure. Becavior, peripheral blood, biochemical and morphologic parameters were assessed in the laboratory animals exposed. The response appeared to correlate with individual and typologic features of the examinees.

[The role of the sex hormones in regulating the spermatogenesis process in different strains of mice irradiated at low doses of gamma quanta]. / Rol' polovykh gormonov v reguliatsii protsessa spermatogeneza u myshei raznykh linii, obluchennykh v malykh dozakh gamma-kvantami.

Intact BALB/c and CBA mice distinct in the total number of germ cells and testosterone level in blood plasma were exposed to doses of 0.1 and 0.25 Gy. Being tested 4-8 days after irradiation the BALB/c mice display compensatory-protective reaction which promote the maintenance of the germ cell number by active division of all spermatogonia types including the reserve ones. The CBA mice use the reserve later and only when the cells have reduced their proliferation activity or died. Testosterone plays a significant role in the process as the increase in its concentration stimulates proliferation activity and promotes mitosis block.