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Testosterone and testosterone free index in mild ankylosing spondylitis: relationship with bone mineral density and vertebral fractures.

OBJECTIVE: To determine the androgen status of men with mild ankylosing spondylitis (AS) and to evaluate the relationship of sex hormones with bone mineral density (BMD) and vertebral fractures. METHODS: Fifty-six male patients with mild AS were studied. All patients had BMD measured by dual x-ray absorptiometry (DXA) of the lumbar spine and hip, and had radiographs of the thoracic and lumbar spines. Radiographs were evaluated morphometrically, and vertebral fractures were defined using established criteria. Serum total testosterone, sex hormone binding globulin (SHBG), follicle stimulating hormone (FSH), and luteininzing hormone (LH) were measured in the patients with AS and 52 age matched controls. Testosterone free index (TFI) was calculated. RESULTS: There was a small, not significant reduction in serum total testosterone in patients with AS compared to controls [16.02 (5.0) vs 21.0 (6.2) nmol/l]. Serum SHBG was significantly lower in patients with AS [27.29 (10.6) vs 35.0 (13.0) nmol/l; p < 0.001] compared to controls. There was no significant difference in the mean TFI between patients and controls [58.7 (21.2) vs 60 (22.2) nmol/l; p > 0.05] or in the levels of LH and FSH. No significant correlation was found between sex hormones, BMD, and vertebral fractures in patients with AS. CONCLUSION: Sex hormones are not altered significantly in patients with mild AS and do not appear to be related to BMD or vertebral fractures. Osteopenia in men with mild AS is therefore unlikely to be secondary to hypogonadism.

Adult↗

Isotope effect studies on the mechanism of the cytochrome P-450IIA1-catalyzed formation of delta 6-testosterone from testosterone.

Testosterone metabolism by cytochrome P-450IIA1 results in four metabolites: 6 alpha-hydroxytestosterone; 7 alpha-hydroxytestosterone; 17 beta-hydroxy-4,6-androstadiene-3-one (delta 6-T); and 17 beta-hydroxy-4,6-androstadiene-3-one-6,7-oxide. The epoxide is formed upon further oxidation of delta 6-T, and its formation is in competition with the dissociation of delta 6-T from the active site. The analysis of the KM and Vmax values, as well as the product ratios for testosterone and three selectively deuterated analogs, strongly suggest that delta 6-testosterone formation occurs primarily by initial hydrogen atom abstraction at the 6 alpha-position followed by abstraction of the 7 alpha-hydrogen atom.

Animals↗

[Circadian rhythm of testosterone level in plasma. I. Physiologic 24-hour oscillations of the testosterone level in plasma].

The testosterone level in plasma is measured in 10 males by radioimmunoassay (RIA) at the following times: 07.00 h, 08.00 h, 09.00 h, 10.00 h, 13.00 h, 16.00 h, 19.00 h, 23.00 h and 03.00 h. A circadian rhythm can be noted. Peak levels are reached between 07.00 h and 10.00 h. At 19.00 h testosterone values reach their minimum and rise at night. In the morning between 07.00 h and 10.00 h testosterone levels seem to have a plateau. Between the morning and the evening the values show great differences.

Adult↗

Comparison of the biological effectiveness of injected testosterone propionate and testosterone released from silastic capsules.

The in vitro release and biological effectiveness of silicone rubber implants containing testosterone in orchidectomized male rats was investigated over a period of 20 weeks. A marked reduction in release in 0.9% saline solution could be observed in vitro relative to the incubation time in the medium. The reduction in release was greatest during the first few weeks of the experiment. Rat seminal vesicles and prostates, which were greatly stimulated at the start of the experiment, lost weight corresponding to the release rate in vitro. The implants containing testosterone used here were 4 to 26 times more effective than testosterone propionate injected s.c.

Animals↗

Unconjugated 5 alpha-androstan-3 alpha, 17 beta-diol and 5 alpha-androstane-3 beta, 17 beta-diol in normal and pathological human seminal plasma. Comparison with testosterone, 5 alpha-dihydrotestosterone and testosterone-glucosiduronate.

By means of specific RIA unconjugated 5 alpha-androstan-3 alpha, 17 beta-diol (3 alpha-diol) and 5 alpha-androstane-3 beta, 17 beta-diol (3 beta-diol) have been estimated for the first time in normal and pathological human seminal plasma. Testosterone, 5 alpha-dihydrotestosterone and testosterone-glucosiduronate (T, DHT, TG) have been determined simultaneously. On average a significant decrease of both diols was established in seminal plasma obtained from males suffering from oligozoospermia, azoospermia, asthenozoospermia and teratozoospermia. The decrease of 3 beta-diol was more pronounced. A significant diminution in DHT concentrations was found only in severe oligozoospermia. Significantly lowered concentrations of testosterone were detected in severe oligozoospermia and in teratozoospermia. However, DHT levels in teratozoospermia were found on average within normal ranges. TG exhibited no significant deviations.

Adolescent↗

Effect of human chorionic gonadotropin on the plasma levels of testosterone, estradiol, sex hormone binding globuline and free testosterone in Klinefelter syndrome.

Preliminary experiments showed that a course of 3 X 5000 IU Human Chorionic Gonadotropin (HCG) every alternate day in 5 patients with Klinefelter Syndrome caused increment in the circulating levels of testosterone, estradiol, and Sex Hormone Binding Globuline (SHBG). The levels of free testosterone, however, declined in 3 subjects and recorded no change in the remaining two. Estradiol/testosterone ratio on day 0 showed high correlation (r = 0.853) with augmented SHBG. It has been postulated that higher amount of SHBG is perhaps potentiating a reduction in the bioavailability of testosterone.

Adult↗

Detection of anabolic steroid administration: ratio of urinary testosterone to epitestosterone vs the ratio of urinary testosterone to luteinizing hormone.

Our goal in this study was to determine whether the urinary ratio of testosterone to luteinizing hormone (T/LH) as an indicator of exogenous anabolic steroid (AS) use is superior to the urinary ratio of testosterone to epitestosterone (T/E). After 2 weekly placebo injections, 19 subjects were given testosterone cypionate (TC) injections of 250 or 500 mg/week for 14 weeks followed by 14 weekly placebo injections. Patients were considered to have ceased taking TC if they tested negative 9 weeks after their last injection. For detection of illicit or supraphysiological TC (AS) use, the urinary T/E ratio of > or = 6 yielded a false-negative rate of 46% and a false-positive rate of 4%. However, a urinary T/LH ratio of > or = 30 produced a false-negative rate of only 24% and a false-positive rate of 13%. We conclude that the urinary T/LH ratio of > or = 30 is a more sensitive marker of AS use than the urinary T/E ratio of > or = 6 and remains sensitive for twice as long as urinary T/E.

Adolescent↗

Comparison between testosterone enanthate-induced azoospermia and oligozoospermia in a male contraceptive study. V. Localization of higher 5 alpha-reductase activity to the reproductive tract in oligozoospermic men administered supraphysiological doses of testosterone.

Sex steroid contraceptive regimes result in incomplete suppression of spermatogenesis in 30-45% of Caucasian men. The basis for this is unclear, but differences in the activity of 5 alpha-reductase (5 alpha R) have been demonstrated. Two isoforms of 5 alpha R have been described: 5 alpha R1 is found in skin, whereas the predominant from in reproductive tissues is 5 alpha R2. To investigate possible contributions of these isoenzymes, we have investigated androgen-dependent changes in seminal plasma androgens (5 alpha R2) and sebum production (5 alpha 1) during administration of a supraphysiological dose (200 mg IM weekly) of testosterone enanthate (TE) to 33 normal men. Eighteen men rapidly (< 20 weeks treatment) became azoospermic, the remainder having a mean sperm density of 2.0 +/- 0.6 x 10(6) at that time. The concentrations of testosterone and 3 alpha, 17 beta-androstanediol glucuronide (AdiolG) were lower in seminal plasma than in blood but rose by a similar degree (100%) after 16 weeks TE treatment in both groups. There were no differences in seminal-plasma concentration of testosterone or AdiolG between azoospermic and oligozoospermic responders, either pretreatment or after 16 weeks TE treatment. Although the concentrations of dihydrotestosterone (DHT) were similar in seminal plasma and blood pre- and posttreatment, there was a selective increase in seminal plasma DHT concentration in the oligozoospermic responders from 2.12 +/- 0.29 to 2.94 +/- 0.33 nmol/L (P < 0.05), while there was no significant change in the azoospermic responders (2.18 +/- 0.31-2.54 +/- 0.27 nmol/L) after 16 weeks of TE treatment. Dihydrotestosterone in seminal plasma is primarily derived from 5 alpha R activity in the epididymis. The concentration of prostaglandin E2 (PGE2) in seminal plasma was unchanged during TE treatment. Sebum excretion was increased during TE treatment, but there were no difference between azoospermic and oligozoospermic responders pretreatment or after 16 weeks TE treatment. These results are consistent with the hypothesis that incomplete suppression of spermatogenesis during TE treatment is associated with a relatively higher 5 alpha R activity in the reproductive tract (epididymis and/or testis) during TE treatment. As the predominant form of 5 alpha R in the reproductive tract is 5 alpha R2 (type 2), we conclude that the increase in activity derives from this form of the enzyme, rather than the type 1 form (5 alpha R1) predominantly found in nongenital skin.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

[Effects of testosterone propionate on LH and testosterone concentrations before and after the injection of gonadoliberin in young bulls pre-treated with dexamethasone].

This preliminary study has been performed on four young twin bulls, one pair aged 6 months and the other one aged 12 months. Plasma LH and testosterone were assayed from frequent blood sampling. Testosterone propionate (TP) following dexamethasone treatment did not significantly influence the LH response to gonadoliberin compared to the twin controls, although testosterone concentrations were high in those TP treated animals.

Animals↗

Effects of castration and testosterone treatment on the activity of testosterone-metabolizing enzymes in the brain of male and female zebra finches.

Recently, we described the distribution of testosterone-metabolizing enzymes (i.e., aromatase, 5 alpha- and 5 beta-reductases) in the zebra finch (Taeniopygia guttata) brain using a sensitive radioenzyme assay combined to the Palkovits punch method. A number of sex-differences in the activity of these enzymes were observed especially in nuclei of the song-control system. The hormonal controls of these differences have now been analyzed by gonadectomizing birds of both sexes and by giving them a replacement therapy with silastic implants of testosterone (T). Five nuclei of the song system (Area X [X], nucleus magnocellularis of the anterior neostriatum [MAN], nucleus robustus archistriatalis [RA], nucleus intercollicularis [ICo], hyperstriatum ventrale, pars caudalis [HVc]) and three preoptic-hypothalamic areas (preoptic anterior [POA], periventricular magnocellular nucleus [PVM], and posterior medial hypothalamic nucleus [PMH]) were studied as well as other limbic and control non-steroid-sensitive areas. The activity of the 5 alpha-reductase was higher in males than in females for the five song-control nuclei and was not affected by the hormonal treatments. The overall activity of this enzyme was not sexually dimorphic in POA and PVM. It was higher in males than in females in intact birds only, and was reduced by gonadectomy and enhanced by T. The activity of the 5 beta-reductase was higher in females than in males in all nuclei of the song system and in POA, but was not influenced by the changes in T level. Both sex and treatment effects were observed in the control of aromatase. The production of estrogens was dimorphic (females greater than males) in RA and PMH. It was increased by T in POA, PVM, and PMH, and also in RA. These data show that some of the sex differences in T-metabolizing enzymes result from the exposure to different levels of T in adulthood (e.g., 5 alpha-reductase in POA and PVM or aromatase in PVM), whereas others persist even if birds are exposed to the same hormonal conditions. These are presumably the result of organizational effects of steroids. The steroid modulation of the aromatase might be related directly to the activation of sexual, aggressive, and nest-building behaviors, whereas the stable dimorphism in 5 alpha- and 5 beta-reductase observed in the nuclei of the song system might be one of the neurochemical bases of the sex differences in the vocal behavior of the zebra finch.

Animals↗

Comparison of the growth-promoting effects of testosterone and 7-alpha-methyl-19-nor-testosterone (MENT) on the prostate and levator ani muscle of LPB-tag transgenic mice.

BACKGROUND: 7-alpha-methyl-19-nortestosterone (MENT) is being considered for androgen replacement in testosterone deficient men and as a male contraceptive. Because androgenic effects on the prostate are a major concern, we have evaluated MENT in a transgenic model of prostate cancer. METHODS: LPB-Tag mice were castrated and infused with testosterone (T; 5 or 30 microg/day) or MENT (5 or 30 microg/day) for 4 weeks. Prostate, seminal vesicle, and levator ani muscle (LAM) weights were compared. RESULTS: At an equivalent dose, MENT maintained or stimulated the mean weights of these organs more than T. However, the dorsolateral prostate/LAM ratio of weights did not favor MENT, but DNA/mg tissue and Ki 67 immunostaining suggested that MENT may increase DNA less than T. CONCLUSIONS: MENT is more potent than T in maintaining or stimulating prostate, seminal vesicle, and LAM. Using doses that resulted in comparable stimulation of the levator ani muscle, MENT had similar effect on prostate weight, but increased DNA/mg prostate less than T in this transgenic mouse model of prostate cancer.

Animals↗

Influence of DDT, DDVP and malathion on FSH, LH and testosterone serum levels and testosterone concentration in testis.

Groups of adult male rats were treated with DDT, DDVP or malathion orally for two or three weeks. Body weight and testis weight did not change. FSH and LH levels in serum also remained unchanged, whereas that of testosterone was decreased by DDT. This substance also diminished the concentration of testosterone in the testis. Therefore, the previously observed damage to spermatogenesis by DDT are assumed to be caused by a lack of androgens. Those following treatment with DDVP or malathion seem to be due to a direct cytotoxic effect.

Animals↗

Plasma testosterone concentration in control and testosterone-treated chick embryos.

After testosterone propionate treatment (1 or 2 mg per embryo), plasma testosterone in chick embryos rises to 500 times higher than in control animals, and then progressively diminishes during the following days of incubation. These drastic changes in hormonal status after the TP treatment entails consequences that may be considered pharmacological rather than physiological.

Animals↗

The effectiveness of two oral contraceptives in suppressing plasma androstenedione, testosterone, LH, and FSH, and in stimulating plasma testosterone-binding capacity in hirsute women.

The effectiveness of two oral contraceptives in suppressing plasma androstenedione (A), testosterone (T), LH, and FSH and in stimulating testosterone-estradiol-binding globulin (TeBG) was evaluated in 39 hirsute women. Twenty-seven hirsute women received norethindrone 2 mg.-mestranol 0.1 mg. (Group I) and 12 received norgestrel 0.5 mg.-ethinyl estradiol 0.05 mg. (Group II). Hormone assays were performed before treatment and at the end of 3 weeks of therapy. Ninety percent of the women in both groups had an elevated plasma A and/or T. During treatment, plasma A,T, LH, and FSH were significantly reduced in both groups (p less than 0.01). In Group I, 78% of the women had a normal plasma A and T during treatment. In Group II, 83% of the women had a normal A and T during treatment. There was a greater increase in TeBG in Group I (p less than 0.01). It is concluded that these two oral contraceptives effectively suppressed the hyperandrogenism of most of the hirsute women.

Adolescent↗

Testosterone and avian life histories: the effect of experimentally elevated testosterone on corticosterone and body mass in dark-eyed juncos.

To assess whether alterations in the normal pattern of testosterone (T) secretion might be beneficial or detrimental, we studied a breeding population of dark-eyed juncos in which we elevated T experimentally and measured its effect on potential correlates of fitness. We treated both free-living and captive males with implants that were either empty (C-males, controls) or packed with T (T-males, experimentals). Timing of implant varied and was designed to mimic natural peak breeding levels except that peaks were either prolonged or premature. We bled the birds at recapture and analyzed their plasma, and that of their female mates, for T and corticosterone (B). We also measured body mass and fat score in free-living T- and C-males. In the field, T-implants elevated T and kept it elevated for at least a month. Experimental males also had higher B than controls. In captives, the effect of the implants on plasma T was detectable within 24 hr. B in captive T-males was again higher than in captive C-males. In females, neither T nor B differed between mates of T- and C-males. T-males implanted in early spring lost more mass between implant and recapture in late spring than did controls and also had lower fat scores when recaptured. When implants were inserted in summer, treatment did not influence mass. Elevated T in early spring apparently hastened the transition from the winter to the breeding mode of fat storage. We suggest that prolonged elevation of testosterone might be selected against because of the association between T and B. Premature elevation of T might be costly because of the resultant loss of mass and fat reserves, which could lead to mortality when spring snowstorms prevent access to food.

Adipose Tissue↗

Effects of various doses of testosterone propionate on intratesticular and plasma testosterone levels and maintenance of spermatogenesis in adult hypophysectomized rats.

Adult hypophysectomized rats were maintained on different regimens of testosterone propionate (TP) treatment for 27 days (0.2, 0.4, 0.6 and 1 mg/day) and autopsied 16 hours after the last injection. Blood samples were taken, sex organs were weighed and one testis from each animal was fixed in Bouins fluid for histologic analysis. The other testis and blood were used for testosterone (T) determinations. Both testicular and plasma T were below detectable levels in hypophysectomized control rats. The plasma T level showed a dose response relationship with increasing dose of TP but such was not the case for intratesticular T concentrations. Qualitative and quantitative evaluation of testis sections showed that spermatogenesis was incomplete in rats receiving 0.2 mg TP/day characterized by the absence of step 15 to 19 spermatids, degeneration of some pachytene spermatocytes and a significantly lower yield of B type spermatogonia. Analysis of testis sections from animals treated with 0.4 to 1 mg TP/day showed complete maintenance and maturation of pachytene spermatocytes, meiosis and spermiogenesis. However, even with the highest dose of TP (1 mg/day) the total yield of B type spermatogonia was only about 58% of the intact controls. It is concluded that at least 0.4 mg/day of exogenous TP is essential for qualitative maintenance of spermatogenesis in hypophysectomized rats with an intratesticular T concentration of 17 to 18 ng/gm testis.

Animals↗

The prognostic value of serum estradiol, progesterone, testosterone and free testosterone levels in detecting early abortions.

OBJECTIVE: Hormonal levels in early pregnancy may have predictive value in regard to outcome of pregnancy. In this study, the levels of estradiol (E2), progesterone (P), total testosterone (tT) and free testosterone (fT) were investigated in this respect. MATERIALS AND METHOD: Seventy women with early pregnancies of 6-12 weeks who applied to the hospital for a pregnancy test were included into this study and were divided into three groups according to their final diagnosis. Group 1 consisted of 20 patients with anembryonic pregnancies, group 2 consisted of 20 patients with missed abortion and group 3 had 30 patients with normal pregnancies. Serum levels of E2, P, fT and tT were measured in every patient and the ratio of fT to tT was calculated (fT ratio). RESULTS: E2, P and tT levels in patients with missed abortion or anembryonic pregnancies were significantly lower than those in the normal group, whereas fT ratio was significantly higher. The level of P over 12.3 ng/ml was found to be sensitive and specific with respect to detecting a normal pregnancy (95% and 90%, respectively). All patients whose fT ratios were 1.05 and higher, subsequently miscarried whereas the ones whose fT ratios were lower than 0.84 were considered as normal pregnancies. CONCLUSION: Serum P levels and fT ratio in early pregnancies can be used as a screening test with high sensitivity and specificity to predict a normal pregnancy.

Abortion, Spontaneous↗