R.A. Lobo

5-alpha-reductase activity and risk of prostate cancer among japanese and US white and black males

The incidence of prostate cancer varies widely between countries and ethnic groups. Black-Americans have the highest incidence rates world wide, whereas native Japanese have among the lowest. The reasons for this risk differential are unknown, although we have previously shown that higher circulating testosterone concentrations in young adult black men compared with young adult white men may explain the underlying differences in subsequent prostate cancer incidence between these two populations. We have now compared serum testosterone concentrations in young adult Japanese men with those of young adult whites and blacks, but found no significant differences. However, these white and black men had significantly higher values of 3 alpha, 17 beta androstanediol glucuronide (31% and 25% higher, respectively) and androsterone glucuronide (50% and 41% higher, respectively) than Japanese subjects. These two androgens are indices of 5 alpha-reductase activity. Our results raise the possibility that reduced 5 alpha-reductase activity has a role in producing the low prostate cancer incidence rates among Japanese. This finding may have important implications for prostate cancer prevention.

Consensus on women's health aspects of polycystic ovary syndrome (PCOS)

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in females with a high prevalence. The etiology of this heterogeneous condition remains obscure and its phenotype expression varies. Two, widely cited, previous ESHRE/ASRM-sponsored PCOS consensus workshops focused on diagnosis (published in 2004) and infertility management (published in 2008). The present third PCOS consensus paper summarizes current knowledge and identifies knowledge gaps regarding various womens health aspects of PCOS. Relevant topics addressed-all dealt with in a systematic fashion-include adolescence, hirsutism and acne, contraception, menstrual cycle abnormalities, quality of life, ethnicity, pregnancy complications, long-term metabolic and cardiovascular health and finally cancer risk. Additional, comprehensive background information is provided separately in an extended online publication.

Rare occurrence of ovarian hyperstimulation syndrome in oocyte donors

Objectives: To define the incidence and severity of ovarian hyperstimulation syndrome (OHSS) occurring in oocyte donors. Methods: Women (n = 149) aged 31.3 ± 4.8 years (mean ± S.D., range 21–41 years) participated as designated oocyte donors and underwent 400 consecutive cycles of controlled ovarian stimulation using human menopausal gonadotropin following pituitary downregulation with gonadotropin‐releasing agonist. Patients were monitored by serial transvaginal ultrasound examinations and serum estradiol (E2) determinations. Oocytes (15.6 ± 7.5 per aspiration; range 2–57) were harvested by ultrasound‐directed transvaginal follicle aspiration 36 h following the intramuscular injection of human chorionic gonadotropin (hCG). Follow‐up examination occurred 1 and 2 weeks post‐aspiration. Results: On the day of hCG injection E2 levels ranged from 512 to 13 502 pg/ml (mean 2902.7 ± 1486.9 pg/ml). Over the next few weeks the degree of hyperstimulation in donors was staged: mild 65% (grade I, n = 98; grade II, n = 162); moderate 33.5% (grade III, n = 120; grade IV, n = 14); severe 1.5% (grade V, n = 6; grade VI, n = 0). Associated preaspiration E2 levels were: grade I, 1120 ± 424 pg/ml; grade II, 2084 ± 613 pg/ml; grade III, 3785 ± 1713 pg/ml; grade IV, 5370 ± 1264 pg/ml; grade V, 4286 ± 1100 pg/ml. Worsening OHSS was associated with increasing levels of E2. There were no serious complications and hospitalization was not required. All symptoms resolved within 30 days of aspiration, disappearing by the time of the first menstrual flow in women of grade‐III or lower stage. Conclusion: Although oocyte donors commonly experienced exaggerated levels of serum E2 they rarely (<2%) developed severe OHSS. This may be attributable to their lack of embryo transfer which avoids exacerbating the illness.

Preimplantation adoption: establishing pregnancy using donated oocytes and spermatozoa

The experience of transferring embryos produced through in-vitro fertilization (IVF) utilizing donated oocytes and spermatozoa is described. Recipients (n = 28; aged 38-59 years) received oral micronized oestradiol and i.m. progesterone and were synchronized to donors undergoing ovarian stimulation. Reasons for selecting therapy included advanced reproductive age (> 42 years; n = 21) or hypergonadotrophic hypogonadism (n = 7), combined with severe male factor infertility in 23 couples. Five women were single and without partners. Oocytes were fertilized by cryopreserved spermatozoa designated for use by the recipient. Up to five embryos were transferred transcervically. Supernumerary embryos were cryopreserved. A total of 36 aspirations produced 15.6 +/- 7.3 oocytes per retrieval. In 10/36 cycles (27.8%), embryos were available for cryopreservation. Using fresh embryos, the overall pregnancy rate was 38.9% (14/36), clinical pregnancy rate 33.3% (12/36), and ongoing/delivered pregnancy rate 30.6% (11/36). Three ongoing pregnancies were later established by transferring cryopreserved embryos. Adjusting for these events, the per aspiration overall pregnancy rate per retrieval was 47.2%, clinical pregnancy rate 41.7%, and ongoing/delivered pregnancy rate 38.9%. Implantation rates per individual embryo transferred were 16.6% following fresh embryo transfer. A viable pregnancy was achieved by 14 of 28 women (50% cumulative pregnancy rate). We conclude that using donor oocytes and donor spermatozoa is efficacious and allows couples of whom both members suffer from severe gamete abnormalities and single functionally agonadal women an effective means of achieving pregnancy.

The ratio of androstenedione: 11-hydroxyandrostenedione is an important marker of adrenal androgen excess in women

OBJECTIVE To determine if the ratio of serum androstenedione (A):11 beta-hydroxyandrostenedione (OHA) would be helpful in differentiating adrenal from ovarian hyperandrogenism. DESIGN/SETTING Prospective study of outpatients being evaluated for hyperandrogenism. PATIENTS/PARTICIPANTS Normal women (n = 27), those with hyperandrogenic chronic anovulation (n = 25), and 7 with adult onset of congenital adrenal hyperplasia (CAH) because of 21-hydroxylase deficiency. INTERVENTIONS Fasting serum between 8:00 A.M. and 9:00 A.M. Patients with hyperandrogenic chronic anovulation and CAH received dexamethasone (DEX) 2 mg for 7 days. MAIN OUTCOME MEASURES Serum testosterone (T), unbound T, dehydroepiandrosterone sulfate (DHEAS), A, and 11 beta-OHA by radioimmunoassay. RESULTS Serum 11 beta-OHA and DHEAS were elevated in 52% and 40% of patients with hyperandrogenic chronic anovulation and in 7 of 7 and 1 of 7 patients with CAH. The ratio of A:11 beta-OHA was significantly higher (P less than 0.05) in hyperandrogenic chronic anovulation and significantly lower (P less than 0.05) in CAH compared with controls. Serum A:11 beta-OHA correlated with T (r = 0.58, P less than 0.05). The ratios of A:11 beta-OHA were similar and significantly lower in CAH and hyperandrogenic chronic anovulation patients who were DEX sensitive compared with those who were not DEX sensitive. The ratio correlated with the percentage suppression of T, unbound T, and A after DEX (P less than 0.01). There were no differences with measurements of DHEAS and 11 beta-OHA. Using the mean ratio of controls (1.3) as a cutoff value, the sensitivity of the A:11 beta-OHA in detecting adrenal hyperandrogenism, as assessed by DEX sensitivity, was 100%, the specificity was 84%, and the predictive value was 67%. CONCLUSIONS The ratio of A:11 beta-OHA appears to be an excellent marker for identifying patients with adrenal hyperandrogenism and CAH.

Behavioral stress responses in premenopausal and postmenopausal women and the effects of estrogen

OBJECTIVE: Our purpose was to determine the pattern of reactivity to stress in premenopausal and postmenopausal women and to assess the effects of estrogen. STUDY DESIGN: A behavioral stress test was given to premenopausal (n = 13) and postmenopausal women (n = 36). Biophysical and neuroendocrine responses were measured during and on completion of the stress test. The postmenopausal women were then randomized to placebo or transdermal estradiol treatment for 6 weeks, at which time another behavioral stress test was given. RESULTS: Stress reactivity to math and speech tasks elicited significantly greater systolic blood pressure responses in postmenopausal women compared with premenopausal women (p < 0.05). On retesting, significant biophysical responses that were present during the initial stress testing were still present (p < 0.05) in the placebo group but were blunted with estrogen treatment. Plasma corticotropin, cortisol, androstenedione, and norepinephrine increased during testing to a similar degree in premenopausal and postmenopausal women; this response was maintained after placebo treatment. Postmenopausal women treated with estrogen had blunted responses. CONCLUSION: Significant differences in responses to psychologic stress exist in premenopausal and postmenopausal women. The lack of adaptation may account in part for the increased risk of cardiovascular disease in postmenopausal women. Estrogen appears to blunt the stress-induced response. (AM J OBSTET GYNECOL 1992;167:1831-6.)

Does ethnicity influence the prevalence of adrenal hyperandrogenism and insulin resistance in polycystic ovary syndrome

Does ethnic@ influence the prevalence of adrenal hyperandrogenism and insulin resistance in polycystic ovary syndrome? Carmina E.; Koyama T.; Chang L.; Stanczyk F.Z.; Lobo R.A. USA AM J OBSTET GYNECOL 1992 16716 (1807-1812) OBJECTIVE: Our purpose was to determine the prevalence of adrenal hyperandrogenism and insulin resistance in patients with hyperandrogenic chronic anovulation, also called polycystic ovary syndrome, living in the United States, Italy, and Japan. STUDY DESIGN: Seventy-five women with polycystic ovary syndrome, 25 each from the United States, Italy, and Japan, and IO ovulatory controls were studied. Hirsutism, obesity, and the presence of cystic ovaries were assessed, as were blood levels for estrogen, luteinizing hormone, testosterone, adrenal androgens, and insulin. All patients received an insulin tolerance test to assess insulin resistance. RESULTS: Women from Japan were less obese (P < 0.05) and did not have hirsutism, although the percentage of cystic ovaries (68 to 80%) was comparable. Serum luteinizing hormone, testosterone, and estradiol were similar, but levels of 3a-androstanediol glucuronide, which was elevated in women from the United States and Italy, was normal in women from Japan. The adrenal androgens, dehydroepiandrosterone sulfate and 1 lbhydroxyandrostenedione were elevated in 48 to 64% of the patients and by a similar percentage in the three groups. Fasting insulin was elevated in all groups, but was significantly higher in women from the United States and Italy compared with women from Japan (P < 0.05). However, insulin resistance as assessed by dissociation constant of insulin tolerance test values was significantly elevated but similar in the three groups and occurred in 68% for 76% of patients. CONCLUSION: In polycystic ovary syndrome, although obesity and hirsutism vary according to dietary, genetic, and environmental factors, the prevalence of adrenal androgen excess and insulin resistance appear to be fairly uniform. These results suggest that these factors may be involved in the pathophysiologic features of the disorder.

In vitro fertilization in unstimulated cycles: A clinical trial using hCG for timing of follicle aspiration

In vitro fertilization (IVF) was performed in normally ovulatory women after the follicular phase of an unstimulated cycle. Twenty patients initiated 36 cycles of unstimulated IVF, with serial ultrasound examinations and hCG 10,000 IU given when the follicle was mature. Thirty aspirations were carried out under intravenous sedation with transvaginal ultrasound guidance. One or more oocytes were obtained in 29 aspirations (97%) for a total of 52 oocytes (average 1.7); 37 fertilized (71%), two were polyspermic, and 35 cleaved (67%). Seventeen aspirations (57%) yielded multiple oocytes. All 25 oocytes obtained from dominant follicles fertilized (100%), and 12 of 27 oocytes from secondary follicles fertilized (44%) (P less than .05 versus dominant follicles), with one polyspermic fertilization in each group. Sixteen cycles resulted in a single embryo transfer (ET), eight had two embryos, and one had three embryos transferred (36% multiple ET). Five clinical pregnancies (20% per ET, 17% per retrieval) resulted in four ongoing pregnancies (16% per ET, 13% per retrieval), all singletons. Our results suggest that in selected cases, IVF in unstimulated cycles may be a clinically viable alternative to stimulated cycles, with preliminary success rates in the range of national averages for stimulated cycles.

A preliminary report on oocyte donation extending reproductive potential to women over 40

BACKGROUND Fertility in women 40 years of age or older is decreased, and in those with ovarian failure it is thought to be irrevocably lost. The donation of oocytes to young (less than 35 years old) women with ovarian failure has allowed many considered infertile a chance to become pregnant. In these women gonadal hormone replacement results in an endometrium receptive to implantation. It is not known whether the endometrial response to such replacement is decreased in women over the age of 40. METHODS To test the efficacy of oocyte donation to older women, we enrolled seven women 40 to 44 years old with ovarian failure in a trial of hormone replacement and embryo transfer, using oocytes obtained from women undergoing ovarian hyperstimulation solely for gamete donation. RESULTS Seven stimulated cycles in the donors that were synchronized with nine cycles in the recipients resulted in eight embryo transfers. Five viable pregnancies were established, one with twins. A sixth pregnancy ended in miscarriage. Five normal infants were delivered by cesarean section, and one stillborn infant was delivered vaginally. The outcomes were compared with those in women under the age of 40 with ovarian failure who were also participating in our donor-oocyte program and in infertile ovulating women 40 or older who were undergoing standard in vitro fertilization. No significant differences in rates of implantation or ongoing pregnancy were noted in older women as compared with younger women receiving donated embryos. These rates, however, were higher than the rates in the infertile ovulating women of similar age who were undergoing standard in vitro fertilization. CONCLUSIONS These preliminary results suggest that the endometrium retains its ability to respond to gonadal steroids and provides a receptive environment for embryo implantation and gestation even in older women.

Establishment of a nonanonymous donor oocyte program: Preliminary experience at the University of Southern California

Transvaginal ultrasound-directed oocyte retrieval was performed on eight women functioning exclusively as gamete donors for 10 patients with ovarian failure. Donors included sisters, personal friends, and compensated participants selected by the recipient couple. Oocyte donors underwent controlled ovarian hyperstimulation and transvaginal oocyte aspiration. Thirteen initiated cycles resulted in 11 embryo transfers and six ongoing pregnancies. There were no complications, and all donors stated a willingness to undergo the procedure again. The use of nonanonymous oocyte donation appears both efficacious and efficient and is recommended as an option for achieving pregnancy in women with ovarian failure.