Mean Serum Testosterone Levels Research Articles

Effects of gonadal steroid withdrawal on serum phosphate and FGF-23 levels in men

Fibroblast growth factor (FGF-23) is a novel phosphaturic factor. Current data suggest that serum phosphate, dietary phosphate and 1,25 dihydroxyvitamin D regulate circulating FGF-23 levels in vivo. We examined if hypogonadism-induced increases in serum phosphate are associated with increases in circulating FGF-23 in healthy men in the absence of dietary manipulation. 25 healthy men were administered goserelin acetate (GnRH analog) 3.6 mg subcutaneously every 4 weeks for 12 weeks to induce acute testosterone and estrogen deficiency. Subjects consumed an ad libitum diet. Morning fasting blood and urine samples were collected to measure serum phosphate, serum intact FGF-23, PTH, and the maximum tubular reabsorption of phosphate (T(m)P/GFR) at baseline, weeks 4 and 12. The changes in serum FGF-23 and phosphate at weeks 4 and 12 were compared to baseline using paired t-tests. Goserelin therapy decreased mean serum testosterone levels from 543+/-160 ng/dL to 33+/-15 ng/dL at week 4 (p<0.001), and to 20+/-10 ng/dL at week 12 (p<0.001). Serum phosphate increased significantly from 3.4+/-0.6 mg/dL to 3.9+/-0.4 mg/dL at week 4 (p=0.002), and to 4.3+/-0.4 mg/dL at week 12 (p<0.001). T(m)P/GFR increased significantly from 3.2+/-0.6 mg/dL to 3.6+/-0.5 mg/dL at week 4 (p<0.004), and to 4.1+/-0.6 mg/dL at week 12 (p<0.001). FGF-23 levels, however, did not change during the 12-week study. Gonadal steroid deprivation increased serum phosphate levels in men but did not affect serum FGF-23 concentrations. The absence of any change in circulating FGF-23 suggests that supraphysiologic levels of serum phosphate may be required to stimulate circulating FGF-23 or that FGF-23 production is primarily sensitive to changes in dietary phosphate or 1,25 dihydroxyvitamin D within this physiologic serum phosphate range.

Failure to Maintain a Suppressed Level of Serum Testosterone during Long-Acting Depot Luteinizing Hormone-Releasing Hormone Agonist Therapy in Patients with Advanced Prostate Cancer

Objectives: It was the aim of this study to analyze the failure rates in achieving or maintaining castrate levels of serum testosterone in patients with advanced prostate cancer treated with the 3-month luteinizing hormone-releasing hormone agonist (LH-RH) therapy. Methods:Total serum testosterone was determined in 234 patients with prostate cancer in a cross-sectional study. A subset of 90 patients submitted to radical prostatectomy was used as the control group (group 1), and 144 patients with advanced prostate cancer under androgen suppression therapy were included in the study group (groups 2 and 3). The study group was divided into 93 patients (group 2) treated with 50 mg daily bicalutamide and LH-RH agonist (maximal androgen blockade, MAB) and 51 patients treated with the LH-RH agonist alone (group 3). Median follow-up after androgen suppression was 42 months. The castrate testosterone level was defined below 50 ng/dl. Results: The mean serum testosterone level was 29.1 ng/dl in patients undergoing MAB (group 2) and 29.5 ng/dl in patients treated with the LH-RH agonist (group 3; p > 0.05). In group 1, the mean serum testosterone was 445.2 ng/dl (p < 0.0001). The rate of patients with a serum testosterone level higher than 50 ng/dl was 10.9% in patients undergoing androgen suppression, 10% in patients with MAB treatment and 12.5% in those with LH-RH agonist therapy (p > 0.05). In group 1, 98.9% of the patients had a serum testosterone level higher than 50 ng/dl. Conclusions: A small but clinically significant rate of patients under 3-month LH-RH agonist therapy fail to achieve or maintain castrate testosterone serum levels. This finding supports the need of monitoring testicular response during LH-RH agonist therapy.

Ovarian interstitial YAG-laser: An effective new method to manage anovulation in women with polycystic ovary syndrome

This study was undertaken to assess the effectiveness of transvaginal ultrasound-guided ovarian interstitial laser-coagulation treatment in anovulatory women with polycystic ovary syndrome (PCOS). Nineteen anovulatory women with clomiphene citrate-resistant PCOS underwent ultrasound-guided transvaginal ovarian interstitial YAG-laser treatment. In this study, serum hormonal level, spontaneous ovulation rate, and pregnancy rate were assessed. With a spontaneous ovulation rate of 84.2%, 16 of 19 cases ovulated regularly during the 6-month postoperative period. The mean serums luteinizing hormone and serum testosterone levels in the second, fourth, and sixth postoperative months were significantly lower than preoperative levels: 5.87 +/- 2.04 IU/L versus 13.17 +/- 3.03 IU/L (P < .001) and 2.98 +/- 1.79 nmol/L versus 5.49 +/- 3.23 nmol/L (P < .001), respectively. The mean luteinizing hormone/follicle-stimulating hormone ratio was also significantly lower postoperatively at 1.09 +/- 0.30 compared with the preoperative 2.85 +/- 1.14 (P < .001). There was a cumulative pregnancy rate at 6 months of 32.3% (6/19) among the subjects. No significant operative complications were encountered. The ultrasound-guided transvaginal ovarian interstitial laser treatment may be an effective new method to manage anovulation in PCOS patients.

Transdermal Androgen Therapy to Augment EPO in the Treatment of Anemia of Chronic Renal Disease

Hypogonadism and anemia are common comorbid conditions in dialysis patients. Testosterone replacement may improve such clinical parameters as anemia, sarcopenia, and low libido. Additionally, by increasing hemoglobin levels, testosterone replacement may allow for a dose reduction in recombinant human erythropoietin (rHuEPO), thereby reducing cost. This phase IV, single-center, placebo-controlled, double-blind study assessed the effect of transdermal testosterone on serum testosterone levels, rHuEPO dose required to maintain hemoglobin level, bone mineral content, lean body mass and fat content, cholesterol level, sexual function, and mood. Forty hypogonadal male hemodialysis patients who were administered rHuEPO were randomly assigned to 100 mg of topical 1% testosterone gel (Testim; Auxilium Pharmaceuticals, Norristown, PA) or placebo, applied daily for 6 months. Forty men with a mean age of 56 years and baseline serum testosterone level less than 300 ng/dL (< 10.4 nmol/L) participated in this trial. In men assigned to administration of transdermal testosterone, there was an increase beyond that in the placebo group in mean serum testosterone (77.1 ng/dL [2.7 nmol/L]), dihydrotestosterone (DHT; 0.8 nmol/L), and estradiol levels (6.3 pg/mL [23.0 pmol/L]) and a decrease in mean serum luteinizing hormone levels (-3.1 IU/L). Compared with subjects administered placebo, participants on testosterone replacement therapy did not show an appreciable change in rHuEPO dose (mean difference adjusted for baseline values, 12.6 U/kg/wk; P = 0.73), bone mineral density, lean body mass or fat content, cholesterol level, sexual function, or mood. Daily administration of 100 mg of topical 1% testosterone gel for 6 months failed to significantly increase serum testosterone or DHT levels in hypogonadal men with end-stage renal disease. Treatment with transdermal testosterone did not impact on rHuEPO requirement or clinical parameters in this small placebo-controlled study. Greater serum testosterone levels may be required to show clinical benefit in men with end-stage renal disease.

EC-003 Ovarian interstitial YAG-laser: an effective new method to manage anovulation in women with polycystic ovarian syndrome

Objective: This study was undertaken to assess the effectiveness of transvaginal ultrasoundguided ovarian interstitial laser-coagulation treatment in anovulatory women with polycystic ovary syndrome (PCOS). Study design: Nineteen anovulatory women with clomiphene citrate-resistant PCOS underwent ultrasound-guided transvaginal ovarian interstitial YAG-laser treatment. In this study, serum hormonal level, spontaneous ovulation rate, and pregnancy rate were assessed. Results: With a spontaneous ovulation rate of 84.2%, 16 of 19 cases ovulated regularly during the 6-month postoperative period. The mean serums luteinizing hormone and serum testosterone levels in the second, fourth, and sixth postoperative months were significantly lower than preoperative levels: 5.87 G 2.04 IU/L versus 13.17 G 3.03 IU/L (P ! .001) and 2.98 G 1.79 nmol/L versus 5.49 G 3.23 nmol/L (P ! .001), respectively. The mean luteinizing hormone/folliclestimulating hormone ratio was also significantly lower postoperatively at 1.09 G 0.30 compared with the preoperative 2.85 G 1.14 (P ! .001). There was a cumulative pregnancy rate at 6 months of 32.3% (6/19) among the subjects. No significant operative complications were encountered. Conclusion: The ultrasound-guided transvaginal ovarian interstitial laser treatment may be an effective new method to manage anovulation in PCOS patients.

No Association of the CAG Repeat Length in Exon 1 of the Androgen Receptor Gene with Idiopathic Infertility in Turkish Men: Implications and Literature Review

While the correlation between the CAG repeat length of the androgen receptor (AR) gene and idiopathic male infertility is still unclear, ethnic background of the population studied may play an important role in this association. The objective of this study was to determine whether changes in the CAG repeat length are associated with spermatogenic defects in Turkish infertile men. Reproductive hormone concentrations and the CAG repeat length in exon 1 of the AR gene in 47 idiopathic infertile men and 32 fertile controls were analyzed. The mean serum luteinising hormone (LH) and follicle stimulating hormone (FSH) levels were significantly higher in the infertile group than those of the control group (p < 0.0001 for both comparisons), whereas the mean serum testosterone level in the infertile group did not differ significantly from that in the control group (p = 0.16). The mean CAG repeat length of the AR gene in the infertile group did not differ significantly from that in the control group (22.28 +/- 0.37 vs 22.41 +/- 0.54, respectively; p = 0.84). In addition, the frequency of having a CAG repeat number (> or = 24) was also comparable between the infertile patients and fertile controls (31.9% vs 40.6%, respectively; p = 0.21). In conclusion, reproductive hormones with elevated LH and FSH, and normal or low testosterone levels were suggestive of partial impairment of testicular function. However, no statistically significant relationship between the length of the CAG repeat and idiopathic impaired sperm production was observed in the Turkish population studied. These results support the findings of previously published European studies, but are contrary to the findings from Caucasian and North American population studies. Thus, ethnicity and genetic backgrounds seem to be important in this association, and studies from a variety of different ethnic and genetic backgrounds using comparable patient subgroups are valuable to further evaluate this association.

Trinucleotide (CAG) repeat length in exon 1 of the androgen receptor gene of Turkish males with idiopathic infertility

Androgens acting via the androgen receptor are required for normal spermatogenesis. The androgen receptor gene (AR) has a repetitive DNA sequence in exon 1 that encodes a polymorphic polyglutamine tract. A link between idiopathic male infertility and expansion of this polymorphic (CAG) tract in the AR has been suggested by several recent studies, whereas several others were unable to demonstrate an association. Thus, ethnic background of the population studied may play an important role in this association. The objective of this study was to determine whether changes in (CAG) repeat length of the AR are associated with spermatogenic defects in Turkish patients with idiopathic male infertility. A prospective case-control study. Forty-seven infertile patients and 32 fertility proven controls were included in this study. Clinical analyses included cause of infertility, semen analysis, and reproductive hormone (LH, FSH, and testosterone) concentrations. Analysis of trinucleotide (CAG) repeat length was performed by polymerase chain reaction (PCR) and sequencing targeting the AR (CAG) tract using blood DNA of each infertile patient and control. Results were statistically evaluated using the Mann-Whitney U-test and the test for difference between two population proportions. P<0.05 was taken as statistically significant for both tests. The mean serum LH level in the infertile group was significantly higher than that of the control group[6.99 ± 0.74 IU/L (range 2.2–13.8) vs. 3.35 ± 0.43 IU/L (range 1.9–5.9), respectively; P<0.0001]. The mean serum FSH level in the infertile group was also significantly higher than that in the control group[13.53 ± 1.87 IU/L (range 3.44–36) vs. 3.54 ± 0.51 IU/L (range 1.1–5.43), respectively; P<0.0001]. In contrast, the mean serum testosterone level in the infertile group did not differ significantly from that in the control group[18.45 ± 1.41 nmol/L (range 3.8–27.8) vs. 21.79 ± 1.92 nmol/L (range 10.3–27.5), respectively; P=0.16]. The mean length of the AR (CAG) tract in the infertile group did also not differ significantly from that in the control group[22.28 ± 0.37 (range 18–29) vs. 22.41 ± 0.54 (range 16–29), respectively; P=0.84]. In addition, the frequency of having a ≥24 AR (CAG) repeat number was also comparable in between the infertile patients and fertile controls[31.9 % vs. 40.6 %, respectively; P=0.21]. The results from analyses of reproductive hormones with elevated LH and FSH, and normal or low testosterone levels are suggestive of partial impairment of testicular function and are in agreement with results from previously published studies. On the other hand, analysis of the AR (CAG) tract length showed no statistically significant relationship between the size of the (CAG) repeat of the polyglutamine tract and idiopathic impaired sperm production in the population studied. The variability of the results by other researchers may be explained by variations of the ethnic backgrounds of the populations studied. In addition, it is highly probable that the infertile males included in previously published reports may represent a heterogeneous group with respect to the cause of defective spermatogenesis.

TESTOSTERONE TREATMENT, AFFECT, AND APPEARANCE: SLIGHT EFFECTS IN NORMAL SUBJECTS

In a randomized double-blind placebo-controlled experiment, 64 women and 26 men applied testosterone and placebo skin creams during two five- to seven-day periods. Subjects provided serum samples for testosterone assay, completed a daily affect measure, wrote projective stories, recorded random samples of everyday speech, provided a guess as to which week they had received testosterone, and were videotaped in a standard setting. The treatment more than doubled subjects' mean serum testosterone level. Testosterone reduced positive affect in both sexes and led to more attractive dress among women but not among men. There was virtually no effect on story-writing, speech, or videotaped behavior, and subjects could not accurately guess which week they had received testosterone.

A six-month, open-label study assessing a new formulation of leuprolide 7.5 mg for suppression of testosterone in patients with prostate cancer

Objective: The safety, efficacy, and pharmacokinetics of monthly subcutaneous injections of a new leuprolide acetate (LA) depot formulation were investigated in patients with advanced prostate cancer. Methods: The 2-part, 6-month (168-day), open-label, multicenter study enrolled male patients diagnosed with adenocarcinoma of the prostate (Jewett stage C or D). LA-2500 7.5-mg (a new subcutaneous depot formulation containing 7.5 mg of LA) injections were administered at monthly (28-day) intervals. The primary efficacy parameter was total serum testosterone level. A breakthrough response was defined as a single testosterone measurement >50 ng/dL after achieving castration testosterone levels. Testosterone was isolated from sera by alumina column chromatography and measured by radioimmunoassay (RIA). LA was purified by solid-phase extraction and high-performance liquid chromatography and was then quantitated by RIA. Results: One hundred seventeen of the 120 enrolled patients completed the 6-month study. Three patients withdrew for reasons not related to treatment. LA had a mean (SD) maximal concentration of 26.3 (12.6) ng/mL at 4.66 (1.44) hours and was detected for a mean of 37 days (range, 28–49 days). By day 28, 94.1% (112/119) of the patients achieved medical castration (serum testosterone ≤50 ng/dL). By day 42, 100.0% (118/118) of the patients remaining in the study had serum testosterone levels ≤50 ng/dL and 97.5% (115/118) had levels ≤20 ng/dL. At study completion, the mean (SD) serum testosterone level was 6.12 (4.3) ng/dL (range, 3.0–27.0 ng/dL). No breakthrough or acute-on-chronic responses were reported throughout the study. From baseline to month 6, mean (SD) luteinizing hormone level decreased from 8.0 (7.3) mIU/mL to 0.09(0.1) mIU/mL, and mean (SD) prostate-specific antigen level decreased from 32.9 (86.3) ng/mL to 3.2 (12.0) ng/mL. Treatment-related adverse events were reported by 74.2% (89/120) of patients, the most common being hot flashes (56.7%). Conclusion: This 6-month, open-label, noncontrolled study showed LA-2500 7.5-mg depot was well tolerated and maintained testosterone suppression ( ≤50 ng/dL) in the patients completing the study without any testosterone breakthrough responses.

Serum levels of androgens and migraine in postmenopausal women.

Female hormones are thought to be of importance in the aetiology of migraine, which is more common in women than in men. Little attention has been paid to androgens. This study investigates the associations between migraine and serum levels of androgens in postmenopausal women not taking oestrogens. A case-control study was carried out among women participating in a mammography screening program. A neurologist clinically assessed the participants. Headache criteria proposed by the International Headache Society were used. Each of the 15 women with migraine was matched to three controls by time since menopause and by body mass index. Serum levels of androstenedione and total testosterone were measured by radioimmunoassays. Free testosterone was calculated from total testosterone, immunoassayed sex hormone-binding globulin and albumin. The mean+/-S.D. serum level of androstenedione was 2.7+/-1.1 nmol/l and 3.4+/-1.9 nmol/l in cases and controls respectively. The mean serum level of testosterone was 0.8+/-0.4 nmol/l and 1.0+/-0.5 nmol/l in cases and controls respectively. The mean serum level of free testosterone was 12.5+/-8.5 pmol/l and 14.0+/-7.9 pmol/l in cases and controls respectively. Conditional logistic regression analysis was used to test for differences in serum levels of androstenedione, total testosterone and free testosterone between cases and controls. No statistically significant differences were found. To conclude, there was no evidence in this study that differences within normal levels of androgens play an important role in the aetiology of migraine in postmenopausal women not taking oestrogens.

Prognostic value of the clinical and laboratory evaluation in patients with nonmosaic Klinefelter syndrome who are receiving assisted reproductive therapy

Objective: To characterize clinical and laboratory findings in nonmosaic 47,XXY patients that may help to predict spermatogenetic activity in their testicles. Design: Prospective study. Setting: Assisted reproductive technology program. Patient(s): Twenty patients with nonmosaic Klinefelter syndrome who underwent testicular sperm retrieval for IVF. Main Outcome Measure(s): The correlation between basal FSH, LH and testosterone levels, mean testicular volume, and results of the hCG test and presence or absence of sperm after testicular sperm extraction (TESE). Result(s): Sperm was found in nine patients (45%). The mean testicular volume was 7.8 ± 2.5 mL in men with sperm after TESE and 5.6 ± 1.2 mL in those without sperm after TESE; corresponding testosterone levels were 3.5 ± 1.2 ng/mL and 1.7 ± 0.8 ng/mL. Serum levels of FSH and LH did not significantly differ between groups. After the hCG test, the mean serum testosterone level was 16.0 ± 6.3 ng/mL in men with sperm after TESE and 6.7 ± 5.6 ng/mL in those without sperm. Conclusion(s): Testicular volume, testosterone levels, and results of the hCG test are important predictive factors of spermatogenesis in patients with nonmosaic Klinefelter syndrome.

Use of GnRH agonist and human chorionic gonadotrophin tests for differentiating constitutional delayed puberty from gonadotrophin deficiency in boys.

The differentiation of constitutional delayed puberty (CDP) from gonadotrophin deficiency (GD) in boys at referral poses a difficult challenge. The effectiveness of the GnRH agonist (GnRH-a) test in distinguishing between the two conditions was evaluated and compared with findings of the GnRH and hCG stimulation tests. PATIENTS, METHODS AND DESIGN: The study sample included 32 prepubertal boys aged 14 years or older. Thirteen entered spontaneous puberty within 1 year of referral (group A) and 19 remained prepubertal (group B). All underwent the GnRH test (Relefact, Hoechst AG, 0.1 mg/m2 i.v. in one bolus), GnRH-a test (Decapeptyl, Ferring GmbH, 0.1 mg/m2 s.c.) and hCG stimulation (Chorigon, Teva, 1500 units i.m. on three alternate days) at 1-week intervals. All tests were performed at referral at 0800 h. Blood samples were collected before testing and at 30 and 60 min (GnRH test) or 4 h (GnRH-a) for LH and FSH determination, and before testing and at 4 h (GnRH-a) or on the seventh day (hCG) after stimulation for serum testosterone measurement. The LH response to GnRH-a and the testosterone response to hCG stimulation were significantly higher in group A (LH, mean +/- SD 20.4 +/- 7.5 mIU/ml, range 10.8-32.6; testosterone, mean +/- SD 18.0 +/- 5.9 nmol/l, range 9.4-26, P < 0.0001) than in group B (LH, mean +/- SD 2.3 +/- 2.0 mIU/ml, range 0.7-6.9; testosterone, mean +/- SD 1.0 +/- 0.7 nmol/l, range 0.7-3.2), with no overlap between the groups. The cut-off for the LH response to GnRH-a was 8.0 mIU/ml, and for the testosterone response to hCG, 8 nmol/l. There were also significant differences between the groups in mean basal serum LH and FSH (LH, 1.1 +/- 0.5 vs. 0.6 +/- 0.2 mIU/ml, P < 0.05; FSH, 2.2 +/- 2.0 vs. 0.4 +/- 0.3 mIU/ml, P < 0.02) and their response to GnRH (LH, 11.4 +/- 4.4 vs. 2.7 +/- 1.1 mIU/ml, P < 0.0001; FSH, 5.1 +/- 3.4 vs. 2.5 +/- 2.4 mIU/ml, P < 0.0001), and mean serum testosterone level at 4 h after GnRH-a administration (1.9 +/- 1.0 vs. 0.9 +/- 0.4 nmol/l, P = 0.002), but all showed a great overlap in range. Mean age, testicular volume and basal serum testosterone levels were similar in the two groups at referral. One year later, the testicular volume of group A (5.0-12.0 ml) was significantly larger than that of group B (1.0-3.0 ml, P < 0.0001), which remained unchanged on re-examination 3.0 +/- 0.5 years later. The GnRH-agonist test and the repeated-injection hCG test are reliable diagnostic tools for differentiating CDP from GD in boys.

Early hormonal changes during valproate or carbamazepine treatment: a 3-month study.

Long-term treatment with valproate (VPA) or carbamazepine (CBZ) may induce reproductive endocrine disorders in patients with epilepsy. Serum concentrations of reproductive hormones were studied in 17 women and 22 men with recently diagnosed epilepsy before they started either VPA or CBZ medication, and 1 and 3 months later. No weight gain or clinical signs of hormonal disorders were observed during the follow-up. The mean serum levels of testosterone, luteinizing hormone, follicle-stimulating hormone, and sex hormone-binding globulin (SHBG) increased, and dehydroepiandrosterone sulfate (DHEAS) decreased, in women starting VPA. Serum testosterone levels increased in half of the women on VPA. Serum concentrations of progesterone and dehydroepiandrosterone increased, and gonadotropins decreased, in men on VPA during the follow-up. Serum SHBG levels increased and DHEAS decreased during the first months of CBZ treatment in both sexes. In addition, the free-androgen index decreased in men after starting CBZ. Hormonal changes occur after only 1 month's use of VPA or CBZ. VPA-treatment seems to be associated with increased serum androgen levels, but the profile of hormonal changes appears to be different in women than in men. The use of CBZ, in turn, was associated with increased SHBG concentrations and thus with diminished sex steroid function in both sexes. The women with increased serum testosterone levels in the early phase of VPA medication may be at increased risk for VPA-related endocrine disorders later during treatment.

Tissue insulin sensitivity and body weight in polycystic ovary syndrome.

Polycystic ovarian syndrome (PCOS) and obesity both affect insulin sensitivity. This study was designed to investigate the biochemical indices of PCOS and tissue insulin sensitivity in groups of lean and obese women with clinically equivalent degrees of the syndrome, relative to control subjects. A prospective study of in vivo parameters and in vitro study of adipocytes to assess insulin sensitivity. Six lean and 14 overweight patients fulfilling formal diagnostic criteria for PCOS were studied. The degree of hirsutism and amenorrhoea was similar in each group. Eight control subjects were also studied. Endocrine and metabolic parameters were measured in lean and overweight patients with PCOS and control subjects. In vitro studies of adipocyte insulin receptor binding and adipocyte insulin action were performed. The mean plasma LH level was elevated in both groups of PCOS but was significantly higher in the lean group (LH levels were 25.1 +/- 3.1 and 14.5 +/- 1.6 iu/l in lean PCOS and obese PCOS, respectively (P = 0.01)). There was a strong inverse correlation between BMI and LH levels (R = - 0.70, P = 0.001). Fasting insulin levels were elevated in both lean and obese groups (11.5 +/- 2.8 and 26.8 +/- 8.1 mU/l, respectively; P = 0.068). Mean serum testosterone and serum androstenedione levels were also elevated in PCOS compared to control subjects but there was no difference between the two groups of PCOS subjects. Insulin receptor binding in amenorrhoeic subjects with PCOS was low in both lean and obese patients with PCOS but was not significantly different between the two groups (0.79 +/- 0.17% and 0.66 +/- 0.07% per 10 cm2 cell membrane, respectively). Maximally insulin-stimulated rates of 3-O-methylglucose transport were low in both groups compared to previously studied normal subjects (0.96 +/- 0.21 and 0.64 +/- 0.07 pmol per 10 cm2 membrane in lean and obese PCOS subjects, respectively; P = NS). Lean subjects with a given phenotypic expression of PCOS have an equivalent degree of tissue insulin resistance compared to obese PCOS subjects. This implies that the insulin resistance may be a primary feature of PCOS. If this is so, a similar clinical degree of the syndrome may be brought about by genetically determined insulin resistance in lean subjects or by insulin resistance which is secondary to obesity.

Estrogens, Testosterone and Sex Hormone Binding Globulin in Relation to Liver Cancer in Men

Objective: Liver disease in men has been associated with an imbalance of serum estradiol and testosterone. We have evaluated whether serum estradiol and testosterone levels are altered in male liver cancer patients as a result of a specific effect of the disease or because of the associated liver damage. Methods: We have performed a hospital-based case-control study in Greece. The study subjects were all men; 73 patients with hepatocellular carcinoma (HCC), 25 with metastatic liver cancer (MLC) patients and 111 control subjects. Serum estradiol, testosterone and sex hormone binding globulin (SHBG) levels were measured for each subject. Data were analyzed by multiple linear regression. Results: Mean serum estradiol levels were significantly higher among HCC patients as well as among patients with MLC compared to controls. Mean serum testosterone levels were significantly lower among HCC patients as well as among patients with MLC compared to controls. The mean SHBG levels did not differ significantly between the groups. After controlling for the degree of liver damage, the elevated serum estradiol and reduced serum testosterone levels among HCC and MLC patients were no longer significant. Conclusions: Changes in sex steroid levels among patients with liver damage are due to the liver damage per se and not to specific disease processes.

Insulin Resistance in Nonobese Patients with Polycystic Ovary Syndrome

Objectives: Most patients with polycystic ovary syndrome (PCOS) are obese and known to have insulin resistance. Obesity per se is a cause of insulin resistance. This study was performed to determine whether insulin resistance occurs in patients with PCOS in the absence of obesity and acanthosis nigricans. Method: For this purpose, an euglycemic hyperinsulinemic clamp study was performed in 12 nonobese patients with PCOS and in 10 healthy control subjects matched for age and weight. Results: The mean serum testosterone and luteinizing hormone (LH) levels were significantly elevated (4.09 ± 1.32 vs. 1.18 ± 0.53 pg/ml, p < 0.001, and 11.63 ± 5.37 vs. 4.98 ± 2.73 mIU/ml, p < 0.001, respectively), and the serum sex hormone binding globulin level was significantly reduced (40.96 ± 14.94 vs. 73.98 ± 30.40 nmol/l, p < 0.001) in patients with PCOS as compared with the values in control subjects. The mean serum insulin level was also elevated in patients with PCOS as compared with control subjects (32.33 ± 4.98 vs. 19.56 ± 2.21 µU/ml, p < 0.05). The insulin sensitivity was lower in patients with PCOS as compared with the control subjects (200 ± 27.8 vs. 427.8 ± 88.9 µmol kg^–1min^–1, p < 0.001). In patients with PCOS, the serum levels of free testosterone (r = –0.89, p < 0.001) and LH were inversely correlated with the insulin sensitivity (r = –0.63, p < 0.05). Serum follicle-stimulating hormone, prolactin, and dehydroepiandrosterone sulfate levels were similar in both groups. Conclusions: These results indicate that a significant degree of insulin resistance exists in nonobese patients with PCOS and that this insulin resistance is significantly related to serum LH and free testosterone levels. Thus, measures to decrease insulin resistance may have to be considered earlier to decrease the potential risks of developing diabetes mellitus and coronary artery disease at later ages of life in these patients.

Diffuse Stromal Leydig Cell Hyperplasia: A Unique Cause of Postmenopausal Hyperandrogenism and Virilization

A 60-year-old woman presented with diffuse scalp alopecia, hirsutism, and clitorimegaly, and the mean serum testosterone levels were greater than 200 ng/dL. Findings on computed tomography of both adrenal glands were normal. After bilateral oophorectomy, a unique histological picture consisting of diffuse stromal Leydig cell hyperplasia was found. Reinke crystals were present, but neither hilus cell hyperplasia nor stromal hyperthecosis was noted. Sequencing of the 11 exons of the gene for the luteinizing hormone receptor revealed no abnormality. Relevant data suggest that treatment of the postmenopausal woman with hyperandrogenism and virilization is bilateral laparoscopic oophorectomy if she has no pronounced ovarian enlargement or adrenal tumor on imaging. In this setting, an intensive endocrine evaluation or a search for metastatic disease seems to be unnecessary.

Synergistic effects of insulin-like growth factor-I and human chorionic gonadotropin in the rat ovary

Insulin and low doses of lutenizing hormone (LH) activity (human chorionic gonadotropin [hCG]) act synergistically in the rat to produce anovulation, large ovarian cysts, and elevated plasma androstenedione levels. Further, both insulin and insulin-like growth factor-I (IGF-I) affect the ability of gonadotropins to enhance both ovarian theca and granulosa cell function in vitro. The present series of experiments were performed to determine if recombinant human IGF-I (rhIGF-I) can act in a manner similar to insulin when combined with subovulatory doses of hCG in adult normally cycling rats. Fifty-four female Sprague-Dawley rats were randomly assigned to the following treatment groups at the age of 64 days: (A) vehicle alone (controls, phosphate-buffered saline containing 0.09% pig gelatin), (B) twice-daily subcutaneous injections of 0.5 to 3.0 U insulin, (C) twice-daily subcutaneous injections of 1.5 U hCG, (D) both insulin and hCG, (E) twice-daily subcutaneous injections of rhIGF-I (2.5 mg/kg/d), and (F) both hCG and rhIGF-I. After 22 days of treatment, the animals were killed on day 23, trunk blood was collected, and the ovaries were excised for histological study. Eight of 9 control rats and 5 or 6 of 9 rats treated with insulin, hCG, or rhIGF-I alone displayed normal estrus cycles throughout the in vivo treatment period as assessed by daily vaginal smears. In marked contrast, only 1 animal treated with hCG + insulin and 2 animals treated with hCG + rhIGF-I continued to display vaginal smears indicative of normal cycling. Multiple large ovarian follicular cysts were found only in these latter 2 groups (3 of 9 animals in each group). Mean serum testosterone levels were significantly elevated in animals receiving insulin + hCG (0.72 +/- 0.28 v 0.17 +/- 0.03 ng/mL in controls, P = .05). Mean serum androstenedione levels were significantly elevated in animals receiving hCG and animals receiving rhIGF-I + hCG (5.57 +/- 0.99 and 2.39 +/- 0.68 ng/mL, respectively, v0.14 +/- 0.14 ng/mL in controls, P< .01 and P< .05, respectively). We conclude that rhIGF-I and insulin act synergistically with subovulatory doses of hCG to disrupt normal reproductive cycling, elevate serum androgen concentrations, and induce large ovarian cysts in intact adult rats.

Serum testosterone levels in African-American and white men undergoing prostate biopsy

Objectives. Because androgen levels are known to influence prostate growth, we performed a prospective analysis of serum testosterone levels in all African-American and white men who underwent transrectal ultrasound-guided prostate biopsies to evaluate an abnormal digital rectal examination (DRE) and/or serum prostate-specific antigen (PSA) level greater than 4 ng/mL. Methods. From June 1996 through July 1998, we evaluated 453 men (189 African-American and 264 white men) who underwent prostate needle biopsy because of an abnormal DRE or serum PSA greater than 4 ng/mL, or both. All men had morning serum testosterone levels determined just before undergoing prostate needle biopsy. Serum testosterone levels were compared on the basis of the prostate biopsy result (positive or negative for prostate cancer) and by race. Results. A total of 453 men underwent prostate biopsy and had morning serum testosterone levels available for comparison. Of the 264 white men who underwent biopsy, 88 (33%) were found to have prostate cancer compared with 67 (35%) of 189 African-American men who underwent biopsy. In the white men without cancer, the mean serum testosterone level was 380.19 ng/dL; those with prostate cancer had a mean serum testosterone level of 419.52 ng/dL. The mean serum testosterone level in African-American men without cancer was 424.30 ng/dL; it was 386.55 ng/dL in those with prostate cancer. There was no statistical difference in serum testosterone levels based on biopsy result or race. Conclusions. Although several studies have suggested that African-American men have higher serum testosterone levels than white men, these differences were noted only in men 40 years of age or younger. As was noted in our study, after age 40, African-American and white men have comparable serum testosterone levels. In addition, although prostate growth is androgen dependent, we found no difference in serum testosterone levels in men with and without prostate cancer.

EFFECTS ON PUBERTAL GROWTH AND REPRODUCTION IN RATS EXPOSED TO LEAD PERINATALLY OR CONTINUOUSLY THROUGHOUT DEVELOPMENT

The reproductive, endocrine, and growth effects of developmental lead exposure were assessed using a rat model in which 0.6% lead acetate (w/v) was administered in the drinking water ad libitum during different developmental periods to determine if lead actions were a result of direct effects of continuous exposure to the metal ion or secondary to disrupted neonatal "endocrine imprinting." Sprague Dawley rats were exposed to lead: (1) from gestational d 5 through birth; (2) during pregnancy and lactation; (3) during lactation only; (4) from birth through adulthood; or (5) from gestational d 5 through adulthood. Lead effects were measured on the development of aspects of the reproductive system, adult sex steroid levels, and growth rates in both male and female animals. The relative weights of male secondary sex organs in adult offspring were not significantly affected in any of the lead-treated groups. In contrast, female pups exposed to lead from birth through adulthood or from gestational day 5 through adulthood were observed to have significantly delayed vaginal opening and disrupted estrus cycling. These effects on female reproductive physiology were not observed in animals where lead exposure was confined only to pregnancy or lactation. Significant suppression of adult mean serum testosterone levels was only observed in male pups exposed to lead continuously from gestational age 5 d throughout life. Lead decreased birth weight in all animals exposed in utero and mean body weights were significantly decreased in all lead-treated groups up to weaning. Analysis of growth curves revealed that all lead-treated groups had significantly reduced growth rates during lactation. However, in addition, in male pups exposed to lead during pregnancy and lactation, from birth or from gestational age 5 d, growth rates were also significantly reduced during puberty. Postpubertal growth rates were unaffected in any lead-treated group. Thus, delayed female reproductive development and suppression of adult male serum testosterone concentration required continuous exposure to the heavy metal. Little evidence was observed for an alteration of "endocrine imprinting" by lead on either reproductive or growth parameters. Exposure during early development (pregnancy and lactation) resulted in no permanent effects in this model other than small (10%) decreases in the body weight of pups postpuberty.