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Prevalence of adrenal androgen excess in patients with the polycystic ovary syndrome (PCOS) using age-specific DHEAS levels adjusted for body mass and ethnicity
Design: Nonrandomized prospective pilot study conducted in a university hospital General Clinical Research Center (Funded by NIH # M01RR10710). Materials and Methods: Non-pregnant reproductive age women (18-42) with PCOS (n ⫽ 3), body mass index ⬎ 26 kg/m2, and signs of insulin resistance received 1000 mcg chromium picolinate daily. Glucose disposal rate (Rd) was measured at baseline and 2 months by euglycemic hyperinsulinemic clamp with heated hand technique. Lean body mass was measured by DEXA. Other endpoints included LH / FSH ratio, body mass index, waist-hip ratio, and documentation of subjective symptoms by menstrual calendar. Results: Rd improved by a mean of 29.5% (range ⫺6% to 69%) after 2 months chromium supplementation. The greatest improvements occurred in the most insulin resistant subjects. No significant changes occurred in body mass index, waist hip ratio, or LH / FSH ratio or subjective symptoms. One amenorrheic subject initiated spontaneous menses. Conclusions: Chromium picolinate may be worthy of further investigation as an alternative or adjunctive insulin sensitizer in PCOS, given improvements in insulin sensitivity in this small subset of PCOS subjects. Chromium picolinate supplementation, which has few side effects, could have potential as a long term preventive measure against type II diabetes in these high-risk women.
Tuesday, October 14, 2003 4:45 P.M. O-119 Prevalence of adrenal androgen excess in patients with the polycystic ovary syndrome (PCOS) using age-specific DHEAS levels adjusted for body mass and ethnicity. Ashim Kumar, Alfred A. Bartolucci, Ricardo Azziz. Dept. of Ob/Gyn, UCLA/Cedars-Sinai Medical Ctr, Los Angeles, CA; Dept. of Biostats & Biomathematics, Univ of Alabama at Birmingham, Birmingham, AL; Dept. of Ob/Gyn & Medicine, UCLA/Cedars-Sinai Medical Ctr, Los Angeles, CA. Objective: To determine the prevalence of adrenal androgen excess in PCOS using normative values adjusted for age, body mass index (BMI), and race. Design: Prospective controlled study. Materials and Methods: A total of 165 (89 Black and 96 White) agematched healthy eumenorrheic non-hirsute women (controls) were recruited by age (15-19 yrs, 20-29 yrs, 30-39, yrs, and 40-45 yrs); 213 (27 Black and 186 White) women with PCOS were recruited consecutively. After informed consent, serum was obtained for the measurement of total testosterone (T), free T, androstenedione (A4), DHEAS, and sex hormonebinding globulin (SHBG). Results: The mean total and free T, A4, and DHEAS levels, and BMI, were higher in PCOS than control women. The DHEAS levels were adjusted for BMI in all subjects. Black controls had a higher mean BMI (29.2 kg/M2 vs. 25.7 kg/M2, resp.) and a lower mean BMI-adjusted DHEAS value (1216 ng/mL vs/ 1288 ng/mL) than their White counterparts. Using the BMI-adjusted DHEAS levels we then calculated upper normal limit (90th percentile) levels for each age (15-19 yrs, 20-29 yrs, 30-39, yrs, and 40-45 yrs) and race (Black and White) group, as follows: a) in Blacks: 1427 ng/mL, 1389 ng/mL, 1340 ng/mL, 1255 ng/mL for ages 15-19, 20-29, 30-39, & 40-45 yrs., resp.; b) in Whites: 1446 ng/mL, 1405 ng/mL, 1389 ng/mL, 1455 ng/mL for ages 15-19, 20-29, 30-39, & 40-45 yrs., resp.. When the BMI-adjusted DHEAS levels from PCOS patients were compared to the race and age 90th percentile control value, 9/213 (4.2%) of PCOS patients had DHEAS excess. Conclusion: The prevalence of adrenal androgen excess, as assessed by the circulating DHEAS levels, is much lower than previously estimated when controlling for confounding variables, such as age, ethnicity, and BMI Supported by: NIH grants RO1-HD29364 and K24-HD01346.
Tuesday, October 14, 2003 5:00 P.M. O-120 Increased 17-hydroxyprogesterone (17P) responsiveness to gonadotropin stimulation in hyperthecosis (HT) compared to polycystic ovary
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Abstracts
syndrome (PCOS). Michael H. Dahan, Mickey S. Coffler, Ketan S. Patel, Richard Y. Yoo, Pamela J. Malcom, R. Jeffrey Chang. Univ of CA San Diego, LaJolla, CA. Objective: Both PCOS and HT are syndromes defined by ovarian hyperandrogenism and chronic anovulation. In PCOS, increased LH secretion together with increased theca cell responsiveness to LH is responsible for excess androgen production. In contrast, serum LH levels in HT are normal and circulating androgen levels are generaly higher than those found in PCOS. These observations suggest that theca cell sensitivity to LH in HT is greater than that of PCOS. To begin to address this issue, we compared 17P responses to recombinant human LH (r-hLH) in HT and PCOS. Design: Prospective clinical study, approved by the human protection program. Materials and Methods: Sperm 17P responses to multi-dose r-hLH were compared in a 33 y/o woman with HT (BMI: 53), an anovulatory 34 y/o woman with PCOS (BMI: 54) and a 39 y/o normal control (BMI: 27). Initially, each was administered r-hLH, iv, at doses of 0 IU, 1,000 IU and 5,000 IU in a randomized fashion, at least 2 weeks apart. The ovulatory control was studied in the mid-follicular phase of her menstrual cycles. Thereafter, the HT and PCOS patient was subjected to a 10-hour hyperinsulinemic-euglycemic clamp after a 12-hour fast. The rate of insulin infusion was 200 mU/m2/min. Two hours after initiation of the clamp, r-hLH stimulation at a dose of 1,00 IU was repeated. Frequent blood samples were obtained prior to and after administration of r-hLH for measurement of gonadotropins and steroid hormones. Results: As expected mean baseline serum 17P levels were greatest in PCOS (0.92 ⫾ 0.07 ng/ml), while levels in HT (0.61 ⫾ 0.02 ng/ml) were greater than those in the control (0.33 ⫾ 0.04 ng/ml). In the HT patient significant (p ⬍ .005) incrimental changes in 17P were observed with increasing doses of r-hLH. Integrated 17P response were 0.61 ⫾ 0.02, 1.16 ⫾ 0.09, and 2.25 ⫾ 0.35 ng/ml following 0, 1,000 and 5,000 IU, respectively. However, the PCOS patient did not demonstrate changes in mean 17P stimulation in response to increasing doses of r-hLH. Between HT and PCOS, 17P response to 1,000 IU r-hLH stimulation were equivalent. However, in HT the peak 17P response to 5,000 IU r-hLH was 4 fold greater than that of the PCOS patient (4.96 vs. 1.3 ng/ml), despite equivalent serum LH levels. At all r-hLH doses 17P stimulation was greater in the HT and PCOS patient when compared to the control. During insulin infusion the PCOS patient failed to exhibit an increase in r-hLH stimulated 17P, whereas in HT the mean 17P response was increased two-fold compared to the response observed without insulin infusion (2.1 ⫾ 0.2 vs. 1.16 ⫾ 0.09 ng/ml, p ⬍ 0.001). Conclusion: These preliminary data suggest that 1) theca cell responsiveness to r-hLH in HT is considerably greater than that of PCOS; 2) in HT insulin enhances r-hLH stimulated theca cell androgen production; 3) in PCOS an effect of insulin on 17P responsiveness to r-hLH was not observed at the dose employed in this study. Supported by: NICHD/NIH through cooperative Agreement [U54 HD12303-20] as part of the Specialized Cooperative Centers Program in Reproduction Research and in part by NIH grant M01 RR00827.
SOCIETY FOR MALE REPRODUCTION AND UROLOGY Tuesday, October 14, 2003 2:00 P.M. O-121 Tattoo of the non-palpable testis mass: A new way to use intra-operative ultrasound guided needle localization for management of nonpalpable testicular lesions. Eric K. Seaman. Saint Barnabas Medical Ctr, West Orange, NJ. Objective: To effect a new approach to the management of non-palpable lesions of the testis, diagnosed by ultrasound. Design: A retrospective review of the management of 5 patients with non-palpable testicular lesions. Materials and Methods: Five men with male infertility were found to have non-palpable testicular lesions. Lesions were diagnosed by scrotal ultrasound. Management approach was geared towards sparing the testis if the lesion was benign. All men underwent inguinal exploration and delivery of the testis in accordance with standard technique for inguinal orchiectomy.
Vol. 80, Suppl. 3, September 2003
Tuesday, October 14, 2003 4:45 P.M. O-119 Prevalence of adrenal androgen excess in patients with the polycystic ovary syndrome (PCOS) using age-specific DHEAS levels adjusted for body mass and ethnicity. Ashim Kumar, Alfred A. Bartolucci, Ricardo Azziz. Dept. of Ob/Gyn, UCLA/Cedars-Sinai Medical Ctr, Los Angeles, CA; Dept. of Biostats & Biomathematics, Univ of Alabama at Birmingham, Birmingham, AL; Dept. of Ob/Gyn & Medicine, UCLA/Cedars-Sinai Medical Ctr, Los Angeles, CA. Objective: To determine the prevalence of adrenal androgen excess in PCOS using normative values adjusted for age, body mass index (BMI), and race. Design: Prospective controlled study. Materials and Methods: A total of 165 (89 Black and 96 White) agematched healthy eumenorrheic non-hirsute women (controls) were recruited by age (15-19 yrs, 20-29 yrs, 30-39, yrs, and 40-45 yrs); 213 (27 Black and 186 White) women with PCOS were recruited consecutively. After informed consent, serum was obtained for the measurement of total testosterone (T), free T, androstenedione (A4), DHEAS, and sex hormonebinding globulin (SHBG). Results: The mean total and free T, A4, and DHEAS levels, and BMI, were higher in PCOS than control women. The DHEAS levels were adjusted for BMI in all subjects. Black controls had a higher mean BMI (29.2 kg/M2 vs. 25.7 kg/M2, resp.) and a lower mean BMI-adjusted DHEAS value (1216 ng/mL vs/ 1288 ng/mL) than their White counterparts. Using the BMI-adjusted DHEAS levels we then calculated upper normal limit (90th percentile) levels for each age (15-19 yrs, 20-29 yrs, 30-39, yrs, and 40-45 yrs) and race (Black and White) group, as follows: a) in Blacks: 1427 ng/mL, 1389 ng/mL, 1340 ng/mL, 1255 ng/mL for ages 15-19, 20-29, 30-39, & 40-45 yrs., resp.; b) in Whites: 1446 ng/mL, 1405 ng/mL, 1389 ng/mL, 1455 ng/mL for ages 15-19, 20-29, 30-39, & 40-45 yrs., resp.. When the BMI-adjusted DHEAS levels from PCOS patients were compared to the race and age 90th percentile control value, 9/213 (4.2%) of PCOS patients had DHEAS excess. Conclusion: The prevalence of adrenal androgen excess, as assessed by the circulating DHEAS levels, is much lower than previously estimated when controlling for confounding variables, such as age, ethnicity, and BMI Supported by: NIH grants RO1-HD29364 and K24-HD01346.
Tuesday, October 14, 2003 5:00 P.M. O-120 Increased 17-hydroxyprogesterone (17P) responsiveness to gonadotropin stimulation in hyperthecosis (HT) compared to polycystic ovary
S46
Abstracts
syndrome (PCOS). Michael H. Dahan, Mickey S. Coffler, Ketan S. Patel, Richard Y. Yoo, Pamela J. Malcom, R. Jeffrey Chang. Univ of CA San Diego, LaJolla, CA. Objective: Both PCOS and HT are syndromes defined by ovarian hyperandrogenism and chronic anovulation. In PCOS, increased LH secretion together with increased theca cell responsiveness to LH is responsible for excess androgen production. In contrast, serum LH levels in HT are normal and circulating androgen levels are generaly higher than those found in PCOS. These observations suggest that theca cell sensitivity to LH in HT is greater than that of PCOS. To begin to address this issue, we compared 17P responses to recombinant human LH (r-hLH) in HT and PCOS. Design: Prospective clinical study, approved by the human protection program. Materials and Methods: Sperm 17P responses to multi-dose r-hLH were compared in a 33 y/o woman with HT (BMI: 53), an anovulatory 34 y/o woman with PCOS (BMI: 54) and a 39 y/o normal control (BMI: 27). Initially, each was administered r-hLH, iv, at doses of 0 IU, 1,000 IU and 5,000 IU in a randomized fashion, at least 2 weeks apart. The ovulatory control was studied in the mid-follicular phase of her menstrual cycles. Thereafter, the HT and PCOS patient was subjected to a 10-hour hyperinsulinemic-euglycemic clamp after a 12-hour fast. The rate of insulin infusion was 200 mU/m2/min. Two hours after initiation of the clamp, r-hLH stimulation at a dose of 1,00 IU was repeated. Frequent blood samples were obtained prior to and after administration of r-hLH for measurement of gonadotropins and steroid hormones. Results: As expected mean baseline serum 17P levels were greatest in PCOS (0.92 ⫾ 0.07 ng/ml), while levels in HT (0.61 ⫾ 0.02 ng/ml) were greater than those in the control (0.33 ⫾ 0.04 ng/ml). In the HT patient significant (p ⬍ .005) incrimental changes in 17P were observed with increasing doses of r-hLH. Integrated 17P response were 0.61 ⫾ 0.02, 1.16 ⫾ 0.09, and 2.25 ⫾ 0.35 ng/ml following 0, 1,000 and 5,000 IU, respectively. However, the PCOS patient did not demonstrate changes in mean 17P stimulation in response to increasing doses of r-hLH. Between HT and PCOS, 17P response to 1,000 IU r-hLH stimulation were equivalent. However, in HT the peak 17P response to 5,000 IU r-hLH was 4 fold greater than that of the PCOS patient (4.96 vs. 1.3 ng/ml), despite equivalent serum LH levels. At all r-hLH doses 17P stimulation was greater in the HT and PCOS patient when compared to the control. During insulin infusion the PCOS patient failed to exhibit an increase in r-hLH stimulated 17P, whereas in HT the mean 17P response was increased two-fold compared to the response observed without insulin infusion (2.1 ⫾ 0.2 vs. 1.16 ⫾ 0.09 ng/ml, p ⬍ 0.001). Conclusion: These preliminary data suggest that 1) theca cell responsiveness to r-hLH in HT is considerably greater than that of PCOS; 2) in HT insulin enhances r-hLH stimulated theca cell androgen production; 3) in PCOS an effect of insulin on 17P responsiveness to r-hLH was not observed at the dose employed in this study. Supported by: NICHD/NIH through cooperative Agreement [U54 HD12303-20] as part of the Specialized Cooperative Centers Program in Reproduction Research and in part by NIH grant M01 RR00827.
SOCIETY FOR MALE REPRODUCTION AND UROLOGY Tuesday, October 14, 2003 2:00 P.M. O-121 Tattoo of the non-palpable testis mass: A new way to use intra-operative ultrasound guided needle localization for management of nonpalpable testicular lesions. Eric K. Seaman. Saint Barnabas Medical Ctr, West Orange, NJ. Objective: To effect a new approach to the management of non-palpable lesions of the testis, diagnosed by ultrasound. Design: A retrospective review of the management of 5 patients with non-palpable testicular lesions. Materials and Methods: Five men with male infertility were found to have non-palpable testicular lesions. Lesions were diagnosed by scrotal ultrasound. Management approach was geared towards sparing the testis if the lesion was benign. All men underwent inguinal exploration and delivery of the testis in accordance with standard technique for inguinal orchiectomy.
Vol. 80, Suppl. 3, September 2003