Biomedical subjects

F Z Stanczyk

Publications and source records attributed to F Z Stanczyk.

At least 91 records · Page 5Linked to original sources

PubMed1994

Alterations in androgen conjugate levels in women and men with alopecia.

OBJECTIVE: To assess levels of androgen metabolites thought to reflect, at least in part, peripheral androgen activity in women with androgenic alopecia and men with premature balding in an effort to determine if a common abnormality exists. DESIGN: Prospective study in various groups of women and men. SETTING: Reproductive Endocrine Clinic at our university medical center. PATIENTS: Ten normal ovulatory female controls and 50 hyperandrogenic women divided on the basis of hirsutism and alopecia as follows: [1] 8 hirsute women with androgenic alopecia; [2] 12 nonhirsute women with androgenic alopecia; [3] 18 hirsute women without androgenic alopecia; and [4] 12 nonhirsute women without androgenic alopecia. Ten normal men and 10 young premature balding men matched for age and weight also were compared. INTERVENTION: Blood was obtained from all subjects. MAIN OUTCOME MEASURE: Comparison of blood hormone levels in the various groups. RESULTS: Serum T, androstenedione, and DHEAS were similarly elevated in hyperandrogenic women with and without alopecia, compared with controls. The female groups were then divided on the basis of hirsutism. Hirsute groups with and without alopecia had similarly elevated levels of unconjugated 3 alpha-androstanediol, 3 alpha-androstanediol glucuronide, 3 alpha-androstanediol sulfate, androsterone glucuronide, and androsterone sulfate compared with controls. In the nonhirsute groups, androgenic alopecia patients were compared with hyperandrogenic females and cycling controls. The androgenic alopecia patients had elevated levels of 3 alpha androstanediol (0.75 +/- 0.12 versus 0.46 +/- 0.1 and 0.41 +/- 0.1 nmol/L), 3 alpha-androstanediol sulfate (200 +/- 31 versus 79.6 +/- 6 and 67.0 +/- 4.0 nmol/L), elevated ratios of 3 alpha-androstanediol sulfate:3 alpha-androstanediol (267 +/- 49 versus 170 +/- 20 and 164 +/- 49 nmol/L), elevated ratios of 3 alpha-androstanediol sulfate:3 alpha-androstanediol glucuronide (32.2 +/- 6 versus 10.8 +/- 1 and 10.0 +/- 1) and lower ratios of 3 alpha-androstanediol glucuronide:3 alpha-androstanediol glucuronide (8.3 +/- 1.8 versus 17 +/- 1.7 and 15.2 +/- 1.6 nmol/L). In men the premature balding group had lower levels of 3 alpha-androstanediol glucuronide compared with the male controls (29.8 +/- 4.4 versus 15.2 +/- 1.6 nmol/L). Also, the ratio of 3 alpha-androstanediol glucuronide:3 alpha-androstanediol was significantly decreased, whereas the ratio of 3 alpha-androstanediol sulfate:3 alpha-androstanediol glucuronide was elevated. CONCLUSIONS: These data provided evidence confirming that enhanced 5 alpha-reductase activity occurs in androgenic alopecia but also suggests that a disorder of androgen conjugation, favoring sulfurylation over glucuronidation, may be a characteristic feature of scalp hair loss.

Adolescent↗

PubMed1994

The route of administration influences the effect of estrogen on insulin sensitivity in postmenopausal women.

OBJECTIVE: To determine the effect of transdermal estrogen on insulin sensitivity in postmenopausal women and to compare this effect with changes observed with oral conjugated equine estrogens. DESIGN: Fourteen postmenopausal women were randomized to receive a transdermal E2 patch, 0.1 mg, for 25 days each month (n = 7) or transdermal E2 with added medroxyprogesterone acetate (MPA), 10 mg, from days 16 to 25 each month (n = 7). An insulin tolerance test (ITT) was performed at baseline and between days 23 and 25 during the 2nd month of treatment to assess insulin sensitivity. Values for the disappearance of glucose (K(itt)) were calculated and compared with values obtained from women receiving 1.25 mg of oral equine estrogens (n = 8). SETTING: University Clinical Research Center. PATIENTS: Healthy postmenopausal women not receiving hormonal replacement. INTERVENTION: Insulin tolerance tests before and after treatment. MAIN OUTCOME MEASURE: Disappearance of glucose and insulin (K(itt)) before and after treatment. RESULTS: Women receiving transdermal E2 alone demonstrated improved insulin sensitivity. The K(itt) glucose values increased by 13.2%, compared with a 23.9% decrease in K(itt) values observed with 1.25 mg of conjugated equine estrogen. The group treated with transdermal E2 and MPA had a reduction in insulin sensitivity. Insulin clearance was enhanced only with transdermal estrogen and was significantly delayed (blunted clearance) with the addition of MPA to transdermal E2 and with oral estrogen. CONCLUSION: We previously demonstrated a bimodal effect of oral equine estrogens on insulin sensitivity with an improvement occurring with the lower dose of 0.625 mg but with a deterioration with the dose of 1.25 mg. Here we suggest that this effect may be related to a first-pass hepatic-portal effect in that transdermal E2 (0.1 mg), which may be equated more closely with the larger dose of oral estrogen (1.25 mg), improved insulin sensitivity. Progestin, however, appeared to attenuate the beneficial effects of transdermal estrogen and may alter the clearance of insulin.

Administration, Cutaneous↗

PubMed1993

Insulin sensitivity is decreased in normal women by doses of ethinyl estradiol used in oral contraceptives.

OBJECTIVE: We determined the independent effects of various doses of ethinyl estradiol used in oral contraceptives or norethindrone acetate, as well as their combination, on insulin sensitivity in normal women. STUDY DESIGN: Thirty-three normal ovulatory female volunteers were recruited for this study. Insulin tolerance tests were performed after carbohydrate loading to determine the kinetic disappearance of glucose and insulin. After initial testing the women were randomized into four groups: ethinyl estradiol 20 micrograms, 35 micrograms, and 50 micrograms and norethindrone 1 mg. Insulin tolerance tests were repeated after 1 month of treatment and again after a second month, when all ethinyl estradiol groups received the addition of norethindrone 1 mg to their doses of ethinyl estradiol. Plasma glucose and insulin were measured, and insulin sensitivity (K(itt) glucose) and the disappearance of insulin (K(itt) insulin) were calculated. RESULTS: All groups were comparable at baseline, and no significant changes in fasting glucose and insulin were evident with treatment. After ingestion of 50 micrograms ethinyl estradiol the K(itt) glucose value decreased significantly (p < 0.03) and ingestion of 20 micrograms and 35 micrograms showed individual changes, but as groups the changes were not statistically significant. All ethinyl estradiol groups combined had a significant decrease in K(itt) glucose (p < 0.01). Norethindrone 1 mg alone did not change K(itt) glucose values, and after the addition of norethindrone to ethinyl estradiol, K(itt) glucose values normalized. K(itt) insulin values were also lower with treatment but were lower with ethinyl estradiol plus norethindrone compared with ethinyl estradiol alone (p < 0.04), suggesting an attenuation of insulin clearance with the progestin. CONCLUSION: Ethinyl estradiol alone decreases insulin sensitivity, and this may occur at lower doses, but norethindrone 1 mg does not appear to do so. However, progestins may alter insulin clearance.

Adult↗

PubMed1993

Single- and multiple-dose pharmacokinetics of a low-dose oral contraceptive in women with chronic renal failure undergoing peritoneal dialysis.

OBJECTIVE: Our purpose was to compare the pharmacokinetic parameters of oral administration of a 35 micrograms ethinyl estradiol, 1 mg norethindrone pill in peritoneal dialysis patients and normal women. STUDY DESIGN: A single-dose study was performed with five patients and four controls, followed by a multiple-dose study with five subjects in each group. Pharmacokinetic parameters were calculated by noncompartmental analysis and statistical analysis performed with Mann-Whitney U testing. RESULTS: There is no difference in the pharmacokinetic parameters for norethindrone in peritoneal dialysis patients compared with normal women. During multiple dosing an increased area under the concentration curve and decreased apparent oral clearance was observed for ethinyl estradiol in peritoneal dialysis patients compared with normal women. CONCLUSION: Peritoneal dialysis patients have decreased apparent oral clearance of ethinyl estradiol, leading to slightly higher serum concentrations compared with women with normal renal function. The clearance of norethindrone is the same in peritoneal dialysis patients and normal women.

Adult↗

PubMed1993

A possible bimodal effect of estrogen on insulin sensitivity in postmenopausal women and the attenuating effect of added progestin.

OBJECTIVE: To determine the effects of estrogen and of added progestin on carbohydrate tolerance in postmenopausal women. DESIGN: An insulin tolerance test (ITT) was used to assess insulin resistance in healthy post-menopausal women and to determine the effects of oral estrogen with and without added progestin on insulin sensitivity. SETTING: A menopause research clinic at a University Medical Center. PATIENTS: Fifteen healthy postmenopausal and nine premenopausal women were studied after having not received any hormone preparations for > or = 4 weeks. INTERVENTIONS: All subjects received a baseline ITT and postmenopausal women were then randomized to receive either 0.625 mg conjugated equine estrogen, 0.625 mg conjugated equine estrogen/10 mg progestin, or 1.25 mg conjugated equine estrogen for 2 months at which time a second ITT was performed. In the former two groups the women were treated for an additional 4 months to assess the long-term effects of treatment and had a third ITT performed at the end of 6 months. MAIN OUTCOME MEASURES: Fasting serum insulin and glucose were measured and K(itt) values were obtained at each visit in each group. RESULTS: Forty-four percent of nonobese healthy postmenopausal women were found to have insulin resistance. The three groups differed significantly in their K(itt) responses. Estrogen replacement improved insulin sensitivity (K(itt) increased by 25%). However, 1.25 mg of conjugated equine estrogen caused a 24.7% decrease in K(itt) values and progestins attenuated the beneficial effects of 0.625 mg conjugated equine estrogen from baseline values (K(itt) decreased by 17.0%). Two- and 6-month values did not differ. CONCLUSIONS: Insulin resistance is prevalent in healthy postmenopausal women. A moderate dose of estrogen appears to increase insulin sensitivity but higher doses may attenuate this benefit and progestins may cause a decrease in insulin sensitivity.

Adult↗

PubMed1993

Premature luteinization as detected by elevated serum progesterone is associated with a higher pregnancy rate in donor oocyte in-vitro fertilization.

Premature luteinization has been reported to be associated with decreased pregnancy rates in patients undergoing in-vitro fertilization. However, the detrimental effect created by a pre-aspiration rise in progesterone is difficult to assess since ovarian stimulation affects both oocyte quality and endometrial receptivity. Therefore, the relationship between premature luteinization and pregnancy rates remains uncertain. To achieve improved control for confounding variables, we studied premature luteinization in ovum donors of proven fertility. A total of 114 consecutive ovum donation cycles using pituitary suppression with a gonadotrophin-releasing hormone agonist followed by gonadotrophin stimulation were examined. Serum progesterone concentration on the day of administration of human chorionic gonadotrophin (HCG) was > 1.2 ng/ml in 29% of patients. Patients were divided into two groups based on this value. There was a significant increase in clinical pregnancy rates per embryo transfer in the group with higher progesterone concentrations (53 versus 25%, P = 0.012), as well as significantly more oocytes obtained at aspiration (19.6 +/- 10.4 versus 13.3 +/- 5.4, P < 0.001), and significantly higher peak serum oestradiol values (3903 +/- 1787 versus 2453 +/- 1232 pg/ml, P < 0.001). There were no significant differences between groups due to age, degree of stimulation or the number of embryos transferred. We conclude that premature luteinization as based on elevated serum progesterone concentration is a common occurrence in oocyte donors, reflects healthy follicular development, and is associated with increased pregnancy rates.

Adult↗

PubMed1992

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.

Adult↗

PubMed1992

A reevaluation of estrogen status in postmenopausal women who smoke.

Hypoestrogenism in postmenopausal smokers has been suggested as the mechanism for the observed decreased risk of endometrial cancer and increased risk of osteoporosis. We have prospectively studied a well-matched group of smokers and nonsmokers and have evaluated their estrogen levels and compared them with existing data from the literature. We conclude that increased adrenal activity resulting in increased androgens, mainly androstenedione, is seen in postmenopausal smokers but that estrogen levels are not decreased. We hypothesize that in nonusers, unlike in users of estrogen, smoking is not associated with changes in estrogen levels and that other mechanisms must be responsible for the epidemiologic observations seen.

Aged↗

PubMed1992

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

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 10 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 3 alpha-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 11 beta-hydroxyandrostenedione 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% to 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.

Adrenal Gland Diseases↗

PubMed1992

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.

Aged↗

PubMed1992

Interrelationship of serum levonorgestrel and sex hormone-binding globulin levels following vaginal and oral administration of combined steroid contraceptive tablets.

Ten women were treated daily with a standard dose contraceptive tablet containing 0.25 mg levonorgestrel (LNG) in combination with 0.05 mg ethinylestradiol. Five women used the tablet vaginally, while the other five used it orally. Blood samples were taken at frequent intervals on the first day of treatment and after 1 and 2 hours on treatment days 7 and 14. Serum LNG levels were measured by radioimmunoassay, and sex hormone-binding globulin (SHBG) was quantitated by charcoal assay. On day 1, peak concentrations of LNG (5.1 ng/ml) occurred within 2 hours in the oral group, whereas in the vaginal group a peak of 2.2 ng/ml was reached after 4 hours. After 24 hours, mean serum concentrations of LNG were 1.1 and 0.69 ng/ml in the oral and vaginal groups, respectively. In both groups, mean LNG concentrations increased dramatically on days 7 and 14 compared to day 1. There was no significant difference between the two groups in LNG concentrations, except after 2 hours on day 1. SHBG levels were increased after one day of treatment. By day 14 of treatment, there was a 3.5- to 4.5-fold rise in SHBG levels from pretreatment values in both groups. However, there was no significant difference in SHBG levels between the two groups throughout the study. A high correlation was found between serum levels of SHBG and LNG in both the vaginal and oral groups. The results suggest that the increase in serum LNG levels in women receiving combined contraceptive tablets either vaginally or orally is due to increased levels of SHBG. Also, the measured concentrations of LNG in the vaginal group are consistent with the previously reported clinical contraceptive efficacy of combined contraceptive tablets administered vaginally.

Contraceptives, Oral, Hormonal↗

PubMed1992

The ratio of androstenedione:11 beta-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.

Adolescent↗

PubMed1992

Estradiol stimulates the secretion of prostacyclin and thromboxane from endometrial stromal cells in culture.

OBJECTIVE: To determine the production of the vasoactive prostaglandins (PGs), prostacyclin, and thromboxane (TX) in endometrial stromal cell cultures and their steroid modulation by sex steroids. DESIGN: Primary stromal cell cultures with steroid modulation in tissues from the follicular and luteal phases of normal women. SETTING: Laboratories of the Division of Reproductive Endocrinology and tissues obtained from normal patients at the Los Angeles County and University of Southern California Medical Center in Los Angeles, California. MEASURES: Stromal cell tissue culture for 14 days. Radioimmunoassay of 6-keto-PGF1 alpha, TXB2, and prolactin (PRL) as well as determination of protein content. RESULTS: Estradiol stimulated 6-keto-PGF1 alpha production more than TXB2. This effect occurred after day 6 and was as much as 10-fold greater in luteal phase tissue. The effect was eliminated by progestins that alone had no effect. This modulatory response was greater in luteal endometrial tissue than in follicular phase tissue. As expected, in these tissues progestin stimulated PRL, an effect opposite to its negative influence on the vasoactive PGs. CONCLUSION: These data provide evidence for a steroid-related influence on the balance of vasoactive PGs in the stroma of the endometrium.

6-Ketoprostaglandin F1 alpha↗

PubMed1992

Cutaneous application of an androstenedione gel as an in vivo test of 5 alpha-reductase activity in women.

OBJECTIVE: Assessment of an in vivo test for 5 alpha-reductase activity using serum markers, 5 alpha-androstane-3 alpha,17 beta-diol glucuronide and androsterone glucuronide, after the cutaneous application of androstenedione (A). DESIGN: An A gel was applied for 6 days to the skin of normal women, male volunteers, and hirsute and nonhirsute patients with polycystic ovarian syndrome (PCOS). Blood samples were obtained at baseline and on day 6 of the A gel application. Blood samples were assayed for A, 5 alpha-androstane-3 alpha,17 beta-diol glucuronide, and androsterone glucuronide. In three hirsute women, the protocol was followed before and after receiving an oral contraceptive (OC) and spironolactone 200 mg/d for 3 months. SETTING: The study was performed in the outpatient clinic of the Division of Reproductive Endocrinology and Infertility, Women's Hospital of the Los Angeles County and University of Southern California Medical Center in Los Angeles, California. PATIENTS, PARTICIPANTS: A total of eight nonhirsute patients with PCOS, seven hirsute patients with PCOS, and six male volunteers were enrolled in the study. Five normal women served as a control group. MAIN OUTCOME MEASURE: Serum A increased after 6 days by a similar magnitude in all groups. Serum androsterone glucuronide showed a significant increase from baseline only in the hirsute group (P < 0.03), whereas the increase in 5 alpha-androstane-3 alpha,17 beta-diol glucuronide was not statistically significant. RESULTS: The ratio of the increases in serum androsterone glucuronide over serum A was significantly higher in the hirsute group (P < 0.02). In the three hirsute patients who were placed on an OC and spironolactone, serum 5 alpha-androstane-3 alpha,17 beta-diol glucuronide and androsterone glucuronide decreased after 3 months and did not increase with application of the gel for another 6 days. CONCLUSION: The cutaneous application of A provides a useful assessment of in vivo 5 alpha-reductase activity. However, because we found that A absorption varied considerably (30% to 62%), we suggest that this in vivo test may not provide more information than baseline determinations of 5 alpha-androstane-3 alpha,17 beta-diol glucuronide and androsterone glucuronide. It may, however, be useful as a parameter for assessing the effectiveness of various treatment regimens for hirsutism.

Administration, Cutaneous↗

PubMed1992

Fetal and maternal endocrine responses to reduced uteroplacental blood flow.

In clinical practice, falling or reduced maternal estrogen levels are commonly regarded as indicators of fetal distress. However, experimental studies in primate animal models demonstrate that changes in maternal estradiol concentrations vary in response to reduced uteroplacental blood flow and are elevated during fetal hypoxemic stress, suggesting an increase in fetal adrenal precursor steroids. We studied the effects of graded reductions in maternal distal aortic blood flow (Qda) on the fetal MCR of dehydroepiandrosterone (D; MCR-D), the fetal production rate of D (PR-D), and changes in maternal and fetal plasma concentrations of D, D sulfate, cortisol, androstenedione, estrone (E1), and estradiol (E2) and in fetal plasma ACTH, PRL, and LH. A continuous i.v. infusion of [7-3H]D was administered to fetuses in five pregnant baboons (Papio anubis) at 155-165 days gestation (term, 184 days) for 270 min. A 50% reduction in mean distal aortic blood flow was imposed after 60 min by means of partial occlusion of the aorta with a snare device, which was released at 180 min. Maternal and fetal blood samples were collected at 10-min intervals from 30-60, 120-180, and 240-270 min. Equilibrium concentrations of [3H]D in fetal plasma were determined, and the MCR-D and PR-D were calculated for each of the three levels of Qda corresponding to the control, occlusion, and release intervals. Concentrations of steroid and peptide hormones in maternal and fetal plasma were determined by RIA, and arterial blood pH, pO2, and pCO2 were measured. Control fetal PR-D (mean +/- SE, 4.4 +/- 2.0 mg/day) rose significantly during aortic occlusion accompanied by fetal hypoxemia (11.8 +/- 3.1 mg/day; P less than 0.05) and remained elevated with release of the aortic constriction (13.8 +/- 2.9 mg/day). Changes in fetal MCR-D were variable and not statistically significant. Among the maternal plasma steroids, only E1 and E2 increased significantly, doubling from control values during aortic occlusion and increasing by another 50% after release (P less than 0.05). There was a significant correlation between fetal PR-D and maternal plasma E2 and E1 concentrations (r2 = 0.76 and 0.71, respectively; P less than 0.01). Fetal hypoxemia was associated with dramatic increases in fetal plasma D, D sulfate, androstenedione, E1, and E2. No significant change occurred in fetal plasma cortisol, which tended to decline throughout the study. We observed a dramatic and sustained increase in fetal plasma ACTH during the period of reduced Qda and for 90 min thereafter, but no change in PRL or LH.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticotropic Hormone↗

PubMed1992

The ovarian contribution to peripherally derived serum C19 conjugates.

While serum markers of peripheral androgen metabolism, such as 5 alpha-androstane-3 alpha, 17 beta-diol glucuronide (3 alpha-diolG) and androsterone glucuronide (AoG), have been highly correlated with adrenal androgen production, the relative ovarian contribution to the pool of various C19 conjugates has not been fully investigated. Our hypothesis was that whereas the ovary may not produce C19 conjugates directly, ovarian androgens, such as testosterone (T) and androstenedione (A), may be used as substrate for peripheral production of these conjugates. To determine whether the ovary contributes directly to the pool of C19 conjugates, blood was obtained from the ovarian and peripheral veins of eight normal women (NW) at hysterectomy. To assess the indirect ovarian contribution to C19 conjugate production, the effect of ovarian suppression and stimulation on circulating 3 alpha-diol and Ao conjugate levels was examined in 10 NW and 10 anovulatory nonhirsute patients with PCO (NH-PCO). Ovarian suppression was carried out with leuprolide acetate (1 mg, sc) daily until the serum estradiol level was 30 pg/mL and was continued thereafter during ovarian stimulation with im human menopausal gonadotropin or FSH. Blood samples were taken before, during, and after GnRH agonist suppression and just before hCG stimulation. Both unconjugated and conjugated androgens were quantified in serum by specific RIAs. No peripheral-ovarian gradients were found for 3 alpha-diol or Ao sulfates (3 alpha-diolS or AoS) or glucuronides. In the NH-PCO group, both T and A levels were elevated, and they were suppressed significantly to levels similar those in NW. With stimulation, T and A levels rose significantly to higher levels than those observed in NW. Both AoS and 3 alpha-diolS, but not AoG and 3 alpha-diolG, decreased significantly with agonist suppression in the two groups; the decrease in levels of AoS and T correlated significantly in the NH-PCO group. With stimulation, the Ao and 3 alpha-diol conjugate levels increased significantly in NH-PCO and were most marked for Ao S and 3 alpha-diol S, which were previously suppressed; the increase in AoG and A correlated highly. Our data suggest that while there is no evidence for the direct ovarian production of C19 conjugates, these markers of peripheral androgen action are influenced by precursors from the ovary, principally A and T.

Adult↗

PubMed1991

The role of prostaglandins in detrusor instability.

To study the role of prostaglandin production by detrusor muscle in women with idiopathic primary detrusor instability, biopsies of detrusor muscle were obtained from 20 women. Nine women had detrusor instability, and 11 women had stable bladders. Prostaglandin F2 alpha and the stable metabolites of prostacyclin and thromboxane A2, namely, 6-keto-prostaglandin F1 alpha and thromboxane B2, respectively, were measured after in vitro incubations of detrusor muscle for 3 hours. A significant reduction in the production of 6-keto-prostaglandin1 alpha in women with detrusor instability was noted. There were no differences in the production of prostaglandin F2 alpha and thromboxane B2, between women with stable and unstable bladders. These results suggest for the first time that women with idiopathic primary detrusor instability may have a deficient production of prostacyclin.

6-Ketoprostaglandin F1 alpha↗

PubMed1991

Is 11 beta-hydroxyandrostenedione a better marker of adrenal androgen excess than dehydroepiandrosterone sulfate?

To determine whether the adrenal androgen 11 beta-hydroxyandrostenedione is a more sensitive and specific marker than dehydroepiandrosterone sulfate, we compared these serum androgens in 81 women with anovulatory hyperandrogenism before treatment, after corticotropin and corticotropin-releasing-factor stimulation, and after short- and long-term dexamethasone suppression. Of all subjects, 65% and 57% had elevated levels of 11 beta-hydroxyandrostenedione (greater than 2.0 ng/ml) and dehydroepiandrosterone sulfate (greater than 2.8 micrograms/ml), respectively. However, 11 beta-hydroxyandrostenedione and dehydroepiandrosterone sulfate levels did not correlate in either the women with hyperandrogenism (r = 0.12) or the 26 normal women (r = 0.29). After 0.25 mg corticotropin was administered intravenously (n = 16), 11 beta-hydroxyandrostenedione increased by 157% +/- 53% (mean +/- SEM), whereas dehydroepiandrosterone sulfate, androstenedione, dehydroepiandrosterone, and cortisol increased by 6% +/- 2%, 46% +/- 10%, 416% +/- 80%, and 2326% +/- 371%, respectively. After intravenous administration of 100 micrograms corticotropin-releasing factor to eight patients, the percent change from baseline level to peak was 148% +/- 26%, 24% +/- 5%, 61% +/- 15%, 117% +/- 15%, and 116% +/- 18% for 11 beta-hydroxyandrostenedione, dehydroepiandrosterone sulfate, androstenedione, dehydroepiandrosterone, and cortisol, respectively. After 2 mg dexamethasone for 3 days (n = 10), 11 beta-hydroxyandrostenedione, dehydroepiandrosterone sulfate, androstenedione, and testosterone were suppressed by 95% +/- 2%, 74% +/- 3%, 51% +/- 9%, and 32% +/- 9%, respectively. Suppression with 0.5 mg dexamethasone for 3 months lowered 11 beta-hydroxyandrostenedione and dehydroepiandrosterone sulfate levels equally by 50% +/- 14% and 62% +/- 12%, respectively. 11 beta-Hydroxyandrostenedione is a useful marker of adrenal androgen secretion with a calculated sensitivity and specificity greater than that of dehydroepiandrosterone sulfate. The greater sensitivity of 11 beta-hydroxyandrostenedione over dehydroepiandrosterone sulfate to adrenal stimulation and suppression suggests its unique diagnostic use.

Adolescent↗