prevalence of adrenal androgen excess in patients with the polycystic ovary syndrome (pcos) using...

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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/m 2 , and signs of insulin resistance received 1000 mcg chromium picolinate daily. Glucose disposal rate (Rd) was measured at baseline and 2 months by euglycemic hyperin- sulinemic clamp with heated hand technique. Lean body mass was mea- sured by DEXA. Other endpoints included LH / FSH ratio, body mass index, waist-hip ratio, and documentation of subjective symptoms by men- strual 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 investiga- tion 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 Med- ical 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) age- matched 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 in- formed consent, serum was obtained for the measurement of total testos- terone (T), free T, androstenedione (A4), DHEAS, and sex hormone- binding 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 ad- justed 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 gonadotro- pin stimulation in hyperthecosis (HT) compared to polycystic ovary 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 hy- perandrogenism 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 hyperin- sulinemic-euglycemic clamp after a 12-hour fast. The rate of insulin infu- sion was 200 mU/m 2 /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 responsive- ness 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-opera- tive ultrasound guided needle localization for management of non- palpable 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 ultra- sound. 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. S46 Abstracts Vol. 80, Suppl. 3, September 2003

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Design: Nonrandomized prospective pilot study conducted in a universityhospital 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 insulinresistance received 1000 mcg chromium picolinate daily. Glucose disposalrate (Rd) was measured at baseline and 2 months by euglycemic hyperin-sulinemic clamp with heated hand technique. Lean body mass was mea-sured by DEXA. Other endpoints included LH / FSH ratio, body massindex, waist-hip ratio, and documentation of subjective symptoms by men-strual calendar.

Results: Rd improved by a mean of 29.5% (range �6% to 69%) after 2months chromium supplementation. The greatest improvements occurred inthe most insulin resistant subjects. No significant changes occurred in bodymass index, waist hip ratio, or LH / FSH ratio or subjective symptoms. Oneamenorrheic subject initiated spontaneous menses.

Conclusions: Chromium picolinate may be worthy of further investiga-tion as an alternative or adjunctive insulin sensitizer in PCOS, givenimprovements in insulin sensitivity in this small subset of PCOS subjects.Chromium picolinate supplementation, which has few side effects, couldhave potential as a long term preventive measure against type II diabetes inthese high-risk women.

Tuesday, October 14, 20034:45 P.M.

O-119

Prevalence of adrenal androgen excess in patients with the polycysticovary syndrome (PCOS) using age-specific DHEAS levels adjusted forbody mass and ethnicity. Ashim Kumar, Alfred A. Bartolucci, RicardoAzziz. 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 Med-ical Ctr, Los Angeles, CA.

Objective: To determine the prevalence of adrenal androgen excess inPCOS using normative values adjusted for age, body mass index (BMI), andrace.

Design: Prospective controlled study.Materials and Methods: A total of 165 (89 Black and 96 White) age-

matched healthy eumenorrheic non-hirsute women (controls) were recruitedby age (15-19 yrs, 20-29 yrs, 30-39, yrs, and 40-45 yrs); 213 (27 Black and186 White) women with PCOS were recruited consecutively. After in-formed consent, serum was obtained for the measurement of total testos-terone (T), free T, androstenedione (A4), DHEAS, and sex hormone-binding 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 ad-justed for BMI in all subjects. Black controls had a higher mean BMI (29.2kg/M2 vs. 25.7 kg/M2, resp.) and a lower mean BMI-adjusted DHEASvalue (1216 ng/mL vs/ 1288 ng/mL) than their White counterparts. Usingthe 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, and40-45 yrs) and race (Black and White) group, as follows: a) in Blacks: 1427ng/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, 1389ng/mL, 1455 ng/mL for ages 15-19, 20-29, 30-39, & 40-45 yrs., resp.. Whenthe BMI-adjusted DHEAS levels from PCOS patients were compared to therace and age 90th percentile control value, 9/213 (4.2%) of PCOS patientshad DHEAS excess.

Conclusion: The prevalence of adrenal androgen excess, as assessed bythe circulating DHEAS levels, is much lower than previously estimatedwhen controlling for confounding variables, such as age, ethnicity, and BMISupported by: NIH grants RO1-HD29364 and K24-HD01346.

Tuesday, October 14, 20035:00 P.M.

O-120

Increased 17-hydroxyprogesterone (17P) responsiveness to gonadotro-pin stimulation in hyperthecosis (HT) compared to polycystic ovary

syndrome (PCOS). Michael H. Dahan, Mickey S. Coffler, Ketan S. Patel,Richard Y. Yoo, Pamela J. Malcom, R. Jeffrey Chang. Univ of CA SanDiego, LaJolla, CA.

Objective: Both PCOS and HT are syndromes defined by ovarian hy-perandrogenism and chronic anovulation. In PCOS, increased LH secretiontogether with increased theca cell responsiveness to LH is responsible forexcess androgen production. In contrast, serum LH levels in HT are normaland circulating androgen levels are generaly higher than those found inPCOS. These observations suggest that theca cell sensitivity to LH in HT isgreater than that of PCOS. To begin to address this issue, we compared 17Presponses to recombinant human LH (r-hLH) in HT and PCOS.

Design: Prospective clinical study, approved by the human protectionprogram.

Materials and Methods: Sperm 17P responses to multi-dose r-hLH werecompared in a 33 y/o woman with HT (BMI: 53), an anovulatory 34 y/owoman 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 and5,000 IU in a randomized fashion, at least 2 weeks apart. The ovulatorycontrol was studied in the mid-follicular phase of her menstrual cycles.Thereafter, the HT and PCOS patient was subjected to a 10-hour hyperin-sulinemic-euglycemic clamp after a 12-hour fast. The rate of insulin infu-sion was 200 mU/m2/min. Two hours after initiation of the clamp, r-hLHstimulation at a dose of 1,00 IU was repeated. Frequent blood samples wereobtained prior to and after administration of r-hLH for measurement ofgonadotropins and steroid hormones.

Results: As expected mean baseline serum 17P levels were greatest inPCOS (0.92 � 0.07 ng/ml), while levels in HT (0.61 � 0.02 ng/ml) weregreater than those in the control (0.33 � 0.04 ng/ml). In the HT patientsignificant (p � .005) incrimental changes in 17P were observed withincreasing 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 inmean 17P stimulation in response to increasing doses of r-hLH.

Between HT and PCOS, 17P response to 1,000 IU r-hLH stimulationwere equivalent. However, in HT the peak 17P response to 5,000 IU r-hLHwas 4 fold greater than that of the PCOS patient (4.96 vs. 1.3 ng/ml), despiteequivalent serum LH levels. At all r-hLH doses 17P stimulation was greaterin the HT and PCOS patient when compared to the control.

During insulin infusion the PCOS patient failed to exhibit an increase inr-hLH stimulated 17P, whereas in HT the mean 17P response was increasedtwo-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 responsive-ness to r-hLH in HT is considerably greater than that of PCOS; 2) in HTinsulin enhances r-hLH stimulated theca cell androgen production; 3) inPCOS an effect of insulin on 17P responsiveness to r-hLH was not observedat the dose employed in this study.

Supported by: NICHD/NIH through cooperative Agreement [U54HD12303-20] as part of the Specialized Cooperative Centers Program inReproduction Research and in part by NIH grant M01 RR00827.

SOCIETY FOR MALE REPRODUCTION AND UROLOGY

Tuesday, October 14, 20032:00 P.M.

O-121

Tattoo of the non-palpable testis mass: A new way to use intra-opera-tive ultrasound guided needle localization for management of non-palpable testicular lesions. Eric K. Seaman. Saint Barnabas Medical Ctr,West Orange, NJ.

Objective: To effect a new approach to the management of non-palpablelesions of the testis, diagnosed by ultrasound.

Design: A retrospective review of the management of 5 patients withnon-palpable testicular lesions.

Materials and Methods: Five men with male infertility were found to havenon-palpable testicular lesions. Lesions were diagnosed by scrotal ultra-sound. Management approach was geared towards sparing the testis if thelesion was benign. All men underwent inguinal exploration and delivery ofthe testis in accordance with standard technique for inguinal orchiectomy.

S46 Abstracts Vol. 80, Suppl. 3, September 2003