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Biomedical subjects

F Z Stanczyk

Publications and source records attributed to F Z Stanczyk.

At least 109 records · Page 6Linked to original sources

Simultaneous measurements of prostacyclin and thromboxane metabolites during the menstrual cycle.

The balance between prostacyclin and thromboxane is known to be important for reproductive and cardiovascular health but has been difficult to quantify. Whereas their stable urinary metabolites, 6-keto-prostaglandin F1 alpha and thromboxane B2, may reflect in part systemic changes, it has been suggested that 2,3-dinor-6-keto-prostaglandin F1 alpha and 11-dehydro-thromboxane B2 more adequately reflect systemic production. Therefore we report for the first time the simultaneous measurements of 6-keto-prostaglandin F1 alpha, thromboxane B2, 2,3-dinor-6-keto-prostaglandin F1 alpha, and 11-dehydro-thromboxane B2 during the menstrual cycle. Timed urine collections were obtained from 18 ovulatory women, aged 22 to 40, during the midfollicular and midluteal phases. Serum estradiol, progesterone, urinary pregnanediol glucuronide, estrone glucuronide, and creatinine also were measured. Prostanoid extraction from urine by C18 and silica Bond Elut columns were then separated by high-performance liquid chromatography before radioimmunoassay. Concentrations of all urinary prostanoids were not significantly different in the follicular phase when compared with the luteal phase. A positive correlation of borderline significance was noted between luteal thromboxane B2 and pregnanediol glucuronide (r = 0.70) and between luteal estrone glucuronide and 2,3-dinor-6-keto-prostaglandin F1 alpha (r = 0.68). A significant correlation was found between follicular estrone glucuronide and the 6-keto-prostaglandin F1 alpha/11-dehydro-thromboxane B2 ratio (r = 0.83, p less than 0.04). These novel normative data suggest an influence of sex steroids on prostacyclin and thromboxane metabolism.

6-Ketoprostaglandin F1 alpha↗

Serum androsterone conjugates differentiate between acne and hirsutism in hyperandrogenic women.

OBJECTIVE: To determine if among hyperandrogenic women acne may be differentiated from hirsutism by markers of peripheral androgen metabolism. DESIGN: Prospective outpatient study of 36 hyperandrogenic women and controls divided into groups based on the presence or absence of significant hirsutism and the presence or absence of moderate to severe acne. Serum levels of adrenal and ovarian derived androgens were elevated but similar in all patient groups. INTERVENTIONS: Measurement of serum androgens including metabolites of 5 alpha-reductase activity: 3 alpha-androstanediol glucuronide and sulfate and androsterone (A) glucuronide and sulfate. RESULTS: 3 alpha-androstanediol glucuronide and sulfate were elevated in all groups (P less than 0.05) and could differentiate between hirsute and nonhirsute patients but were similar in patients with and without acne. Serum A glucuronide and sulfate were only significantly elevated in patients with acne (P less than 0.01) and were higher than levels in controls and hirsute patients without acne. Ratios of precursor androgens to A glucuronide and sulfate were significantly higher in patients with acne compared with patients without acne (P less than 0.05). CONCLUSIONS: Altered peripheral metabolism in acne may favor the formation of A conjugates, which may help differentiate acne from hirsutism among hyperandrogenic women.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Effects of sex steroids on skin 5 alpha-reductase activity in vitro.

Skin 5 alpha-reductase activity is the major factor influencing the manifestation of androgen excess. Although oral contraceptives have been useful for the treatment of androgen excess, little is known of the independent effects of the various progestins and estrogens on inhibition of skin 5 alpha-reductase activity. We incubated minces of normal genital and pubic skin with physiologic concentrations of 3H-testosterone to assess 5 alpha-reductase activity by its conversion to 3H-dihydrotestosterone. In separate experiments, 5 alpha-reductase activity was assessed before and after the addition of progesterone, medroxyprogesterone acetate, levonorgestrel, norethindrone, 17 beta-estradiol, and ethinyl estradiol. Progesterone, levonorgestrel, and norethindrone demonstrated 97 +/- 5.3%, 47.9 +/- 6.3%, and 59 +/- 4.6% inhibition, respectively, of genital skin 5 alpha-reductase activity at 10(-4) mol/L (P less than .01). Medroxyprogesterone acetate, however, failed to affect 5 alpha-reductase activity at similar doses. Estradiol exhibited 40.8 +/- 14.2% inhibition at 10(-4) mol/L (P less than .01), whereas ethinyl estradiol at concentrations from 10(-8) to 10(-4) mol/L failed to inhibit 5 alpha-reductase activity. We conclude that progesterone and the 19-nor-derivatives inhibit 5 alpha-reductase activity at high doses, whereas medroxyprogesterone acetate does not. Therefore, the 19-nor-progestin component may expand the usefulness of oral contraceptives in the treatment of hirsutism by an inhibitory action on skin 5 alpha-reductase activity.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Short-term effects of smoking on the pharmacokinetic profiles of micronized estradiol in postmenopausal women.

Because smoking is associated with an increased risk of osteoporosis, yet a decreased risk of endometrial carcinoma, a state of relative hypoestrogenism induced by smoking has been suggested. However, because previous data are unclear and do not reflect current trends in smoking intensity and estrogen prescriptions, we examined the estrogen profiles of postmenopausal women, by smoking status, both before and after oral micronized estradiol. Baseline levels of estrone, estradiol, estrone sulfate, and estrone glucuronide were similar in nonsmokers and smokers, but unbound (non-sex-hormone-binding-globulin--bound) estradiol was significantly lower in smoking women (p less than 0.05) and sex-hormone-binding-globulin--binding capacity was higher (p less than 0.001). After 1 or 2 mg of micronized estradiol, estrone and estradiol serum profiles were similar but unbound estradiol was significantly lower in women who were smokers (p less than 0.05). Serum estrone glucuronide rose with treatment but was indistinguishable in nonsmokers and smokers. However, maximum changes in serum estrone sulfate were greater in smokers after administration of estrogen, suggesting a hepatic effect. Urinary estrone glucuronide levels increased after 8 hours of oral estrogen but were similar in nonsmokers and smokers with the two doses. It appears that even moderate smoking, as studied here, induces significant changes in hepatic estrogen metabolism and is best reflected by alterations in serum estrone sulfate and sex-hormone-binding-globulin--binding capacity that result in decreased serum unbound estradiol. However, these changes do not appear to require increasing the estrogen dosage to achieve physiologic levels of estrogen in postmenopausal smokers.

Estradiol↗

Metabolism of levonorgestrel, norethindrone, and structurally related contraceptive steroids.

There is limited information on the metabolism of levonorgestrel, norethindrone and structurally related contraceptive steroids. Both levonorgestrel and norethindrone undergo extensive reduction of the alpha, beta-unsaturated ketone in ring A. Levonorgestrel also undergoes hydroxylation at carbons 2 and 16. The metabolites of both compounds circulate predominantly as sulfates. In urine, levonorgestrel metabolites are found primarily in the glucuronide form, whereas norethindrone metabolites are present in approximately equal amounts as sulfates and glucuronides. Of the progestogens structurally related to norethindrone, norethindrone acetate, ethynodiol diacetate, norethindrone enanthate, and perhaps lynestrenol, undergo rapid hydrolysis and are converted to the parent compound and its metabolites. There is no convincing evidence that norethynodrel is converted to norethindrone. Of the progestogens structurally related to levonorgestrel, it appears that neither desogestrel nor gestodene are transformed to the parent compound. However, there is evidence that norgestimate can be, at least partly, converted to levonorgestrel. Further studies on the metabolism of these progestogens are required before we can understand their mechanism of action.

Animals↗

Pharmacokinetic comparison of two triphasic oral contraceptive formulations containing levonorgestrel and ethinylestradiol.

The pharmacokinetics of levonorgestrel (LNG) and ethinylestradiol (EE2) were determined in 24 women (aged 21 to 35 years), following the administration of a single tablet from the second phase of two different triphasic preparations (Triphasil and Trinordiol. Each tablet contained 0.075 mg of LNG and 0.040 mg of EE2. The data were compared to the pharmacokinetics of LNG and EE2 obtained following the oral administration of a hydroalcoholic solution (standard) containing the same steroids and dose. The study consisted of a randomized design in which the three formulations were administered to each of the 24 subjects in a three-period crossover pattern. Blood samples were taken at frequent intervals after dosing. Serum levels of LNG and EE2 were measured by specific radioimmunoassays. The results show that both LNG and EE2 in the Triphasil and Trinordiol tablets are bioequivalent with respect to rate and extent of absorption. Furthermore, LNG, but not EE2, in both tablet formulations was bioequivalent to the solution dose. The serum concentration-time profiles for the three formulations showed that the range of mean peak levels was 2.3-2.8 ng/ml for LNG and 116-159 pg/ml for EE2. These levels were achieved within 2 hours in the majority of subjects. The ranges of mean values calculated for the areas under the curves were 15-16 ng.hr/ml for LNG and 1053-1390 pg.hr/ml for EE2. The ranges of mean values calculated for other pharmacokinetic parameters were: volume of distribution: LNG--1.6-1.8 L/kg, EE2--7.7-9.1 L/kg; clearance: LNG--84-88 ml/hr/kg, EE2--0.67-0.99 ml/hr/kg; half-life: LNG--13-15 hr, EE2--7-12 hrs.

Adult↗

Androstenedione is an important precursor of dihydrotestosterone in the genital skin of women and is metabolized via 5 alpha-androstanedione.

Androgen action is largely determined by the formation of dihydrotestosterone in target tissues. In women, androstenedione is the major precursor of dihydrotestosterone production in female genital skin. The present study was initiated to determine whether androstenedione is converted to dihydrotestosterone primarily via testosterone or 5 alpha-androstane-3,17-dione (5 alpha-androstanedione), and to examine the pathway of androstenedione metabolism in genital skin. Genital skin was obtained from 9 normal premenopausal women and 2 normal men. Each tissue was incubated with [3H]androstenedione in RPMI-1640 medium for 1 h at 37 degrees C in 95% O2/5% CO2. The metabolites were separated and purified by paper partition and thin-layer chromatography. The conversions of androstenedione to 5 alpha-androstanedione and to androsterone were similar (10.45 +/- 1.46 and 11.04 +/- 2.04%/200 mg tissue), and were approx. 12, 8 and 23 times higher than the conversion of androstenedione to testosterone, dihydrotestosterone and 5 alpha-androstane-3 alpha,17 beta-diol, respectively. The male samples showed a similar pattern of metabolism. These data indicate that 5 alpha-androstanedione is the most important intermediate in the conversion of androstenedione to dihydrotestosterone. The data also confirm the importance of 5 alpha-reductase activity over that of 17 beta-hydroxysteroid oxidoreductase activity in the expression of androgen action in women.

Adult↗

Effects of norethindrone on gonadotropin and ovarian steroid secretion when used for cycle programming during in vitro fertilization.

Norethindrone (NET) has been used for cycle programming and may result in attenuated responses to controlled ovarian hyperstimulation. The effects of NET on gonadotropin secretion, its bioavailability to the ovary, and its effect on ovarian steroidogenesis in vivo and in vitro were assessed. Endogenous secretion of luteinizing hormone and follicle-stimulating hormone was attenuated by 59% and 50%, respectively, after 2 weeks of orally administered NET. Twelve hours after a single 10-mg oral dose, significant levels of NET were measured in samples of peripheral (8.8 +/- 1.9 ng/mL) and ovarian venous blood (10.5 +/- 3.1 ng/mL), follicular fluid (7.1 +/- 2.1 ng/mL), and homogenates of ovarian tissue (8.0 +/- 0.6 ng/g). Furthermore, NET was detectable in follicular fluid 2 weeks after its withdrawal (863 +/- 149 pg/mL). However, there were no effects of NET on follicular fluid levels of estradiol and progesterone in vivo or on luteinized granulosa cell steroidogenesis in vitro. We conclude that when used for cycle programming in in vitro fertilization, NET does not inhibit ovarian steroidogenesis but does affect the hypothalamic-pituitary axis.

Adult↗

Random urinary pregnanediol glucuronide measurements in pregnancy: lack of utility for evaluation of first-trimester vaginal bleeding.

Progesterone and its urinary metabolite pregnanediol-3 alpha-glucuronide (PDG) are generally lower in women with abnormal pregnancies compared to those with normal intrauterine gestations. We evaluated the ability of random urinary PDG measurements determined by enzyme immunoassay (EIA) to differentiate normal from abnormal pregnancies. Patients with first-trimester vaginal bleeding (n = 104) were evaluated. Eventual outcomes indicated 39 women had viable intrauterine pregnancies (IUPs), 54 had spontaneous abortions (SABs) and 11 had ectopic pregnancies (EPs). Urinary PDG was significantly lower in SAB and EP compared to IUP patients. However, a wide range of values in IUP patients was noted (3.2-93.3 micrograms/ml), due to varying degrees of patient hydration at presentation. Hence, random measures of urinary PDG demonstrated poor specificity (32.8%) in correctly differentiating normal from abnormal gestations, thus limiting its clinical usefulness.

Female↗

Effect of hydration on random levels of urinary pregnanediol glucuronide.

To determine the effect hydration has upon the relationship between serum progesterone and its urinary metabolite pregnanediol-3 alpha-glucuronide (PDG) we measured spot samples from patients (n = 207) presenting in the 1st trimester of pregnancy. Serum and urine specimens were obtained simultaneously and measured for progesterone and PDG by radioimmunoassay (RIA). Urine specific gravity was also measured at the time of sample collection. Results demonstrated that in samples where the urine specific gravity was greater than or equal to 1.015 there was a strong positive correlation between serum progesterone and PDG (r greater than 0.60, p less than 0.001). However, when urine samples were below a specific gravity of 1.015, serum and urinary steroid values correlated poorly or not at all. We conclude that the measurement of specific gravity should be routinely performed when determining random values of urinary PDG, since only samples in which the urine is adequately concentrated accurately reflect corresponding serum progesterone concentrations.

Adolescent↗

Dehydroepiandrosterone and dehydroepiandrosterone sulfate metabolism in human genital skin.

Genital skin samples were obtained from normal women and men to determine the extent of conversion of dehydroepiandrosterone (DHEA) to dihydrotestosterone (DHT) and other androgen metabolites and to assess sulfatase activity. The skin samples were minced and incubated with 3H-DHEA or 3H-dehydroepiandrosterone sulfate (3H-DHEAS) in medium for 1 hour at 37 degrees C. The following metabolites of DHEA were isolated after extraction and chromatography: 5-androstene-3 beta,17 beta-diol (delta 5-diol), 5 alpha-androstane-3,17-dione (5 alpha-delta 4A), testosterone, DHT, androsterone (A), and 5 alpha-androstane-3 alpha,17 beta-diol. Although the conversion of DHEA to all the metabolites was low, the conversions were higher in men than in women. In women, conversions of DHEA to delta 5-diol and androstenedione (delta 4A) were highest, followed by conversions of DHEA to DHT and 5 alpha-delta 4A, whereas in men the formation of delta 4A and 5 alpha-delta 4A was highest, followed by delta 5-diol and A. There was a significant conversion of DHEAS to DHEA in both women and men, although the sulfatase activity was approximately six times higher in men. We conclude that despite the low conversion of DHEA to DHT, significant androgenecity may result from pathological levels of DHEAS.

Adult↗

Decreased in vitro production of 6-keto-prostaglandin F1 alpha by uterine arteries from postmenopausal women.

Cessation of ovarian function is associated with a marked increased in morbidity and mortality secondary to ischemic heart disease. Estrogen replacement has been shown to impart protection against ischemic heart disease. We hypothesized that estrogen may influence vascular production of vasodilators such as prostacyclin. To investigate this relationship we have measured the production of 6-keto-prostaglandin F1 alpha, and thromboxane B2 by superfused uterine arteries from pre- and postmenopausal women. Arterial specimens from healthy normotensive premenopausal (n = 5) and postmenopausal women (n = 5) were superfused for 5 hours. Production of 6-keto-prostaglandin F1 alpha reached steady state levels by 120 minutes and remained linear for the length of the experiment. Indomethacin (4 x 10(-5) mol/L) added at 120 minutes significantly decreased prostanoid production. In subsequent experiments, 17 beta-estradiol in concentrations of 10, 100, 1000 ng/ml was added to the superfusion media at 120 minutes. Total production of 6-keto-prostaglandin F1 alpha by premenopausal arteries superfused with neat media during the steady state interval (3 hours) was significantly greater than that of postmenopausal specimens (1.25 versus 0.27 ng/mg dry tissue, p less than 0.05). Thromboxane B2 levels were undetectable in spent media. However, the addition of 17 beta-estradiol did not alter production of 6-keto-prostaglandin F1 alpha. These data suggest that arterial production of prostacyclin is significantly decreased in uterine arteries from postmenopausal women, but in this in vitro model system estrogens did not affect vascular prostanoid production.

6-Ketoprostaglandin F1 alpha↗

Androgen sulfate and glucuronide conjugates in nonhirsute and hirsute women with polycystic ovarian syndrome.

Peripheral androgen action largely determines the occurrence of hirsutism in women. Although serum 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-diol) glucuronide signifies skin 5 alpha-reductase activity and has been used as a marker of hirsutism and peripheral androgen metabolism, other C19 androgen conjugates have recently been measured and may also be useful markers of hirsutism in women. In addition to normal controls we studied both hirsute and nonhirsute patients with polycystic ovarian syndrome who had similar levels of circulating androgen precursors. In these three groups we measured various C19 sulfates and glucuronides including serum 3 alpha-diol glucuronide. Serum androgen precursors were elevated, but were equal in the hirsute and nonhirsute patients. Serum androsterone sulfate and glucuronide, and 3 alpha-diol sulfate and glucuronide clearly differentiated the hirsute from the nonhirsute group. Among the conjugates, androsterone glucuronide was most reflective of the difference between the two groups (100.3 +/- 28.0 versus 42.9 +/- 4.0 ng/ml, p less than 0.05). In hirsute compared with nonhirsute patients with polycystic ovarian syndrome, serum 3 alpha-diol glucuronide was increased by the smallest amount (32%), followed by androsterone sulfate (38%), 3 alpha-diol sulfate (59%), and androsterone glucuronide with the largest increase (134%). Serum androsterone glucuronide and 3 alpha-diol glucuronide both correlated with androstenedione and dehydroepiandrosterone sulfate in hirsute women but not in nonhirsute women. These data suggest that besides serum 3 alpha-diol glucuronide, other C19 sulfate and glucuronide conjugates may reflect peripheral androgen action.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Half-life of plasma sex steroid-binding protein (SBP) in the primate.

We have recently shown that the metabolic clearance of testosterone in plasma is directly dependent on sex steroid-binding protein (SBP or SHBG) levels [J. steroid. Biochem. 22, 739 (1986)]. In order to further understand the relationship between these two parameters, we have measured the half-life of SBP in plasma of female rhesus monkeys. SBP was purified to homogeneity from pooled Macaca nemestrina serum, and iodinated with 125I. The labeled protein ([125I]nSBP) was purified by chromatography on DEAE-agarose and fractions identified as immunologically reactive against anti-human SBP were collected. Protein purity of [125I]nSBP was established by SDS gel electrophoresis using an unlabelled Macaca nemestrina SBP as standard. The labeled protein was infused intravenously into two different adult female Macaca mulatta (rhesus) monkeys. Plasma samples were collected at short intervals during the first 24 h after infusion, and then daily for 7-9 days. The clearance profile of labeled SBP in plasma was quantitated by radioactivity measurement and immunoprecipitation. Analysis of the results indicate that the rate of SBP clearance in plasma has two components, the t1/2 (app) of the first component is 7.5 h (r = 0.94), and the t1/2 (app) of the second component is 3.95 days (r = 0.95). Over 90% of the injected 125I-nSBP was removed from plasma within 24 h at a rate corresponding to the t1/2 (app) of the first component. The data indicate that most of the SBP rapidly distributes into extravascular spaces during the first 24 h following infusion, and are consistent with the hypothesis that SBP may be directly involved in sex steroid hormone transport into tissues.

Animals↗

Disparity in the response of sex steroid-binding protein and corticosteroid-binding globulin to thyroxine in the primate.

There is uncertainty regarding the differential effects of thyroid hormone on the circulating levels of sex steroid-binding protein (SBP) and corticosteroid-binding globulin (CBG). Therefore, we studied the effects of elevated thyroxine (T4) on SBP and CBG concentrations in serum in 4 baboon (Papio anubis) infants between 6 and 7 mo of age. The infants were given levothyroxine in increasing doses (25 to 600 micrograms) over a 1-mo period until the peripheral T4 levels were 3-4 times higher than baseline values. Each animal served as its own control. Blood samples were obtained at 2- to 3-day intervals prior to and during treatment. Serum T4 was measured by RIA. SBP and CBG were measured by diethylaminoethyl cellulose filter paper assays. Elevations in serum T4 resulted in a dose-response increase in circulating SBP concentrations with a maximal increase at the 600-micrograms dose of T4 (p less than 0.001). In contrast, significant elevations in peripheral CBG levels occurred with 50 and 100 micrograms of T4 (p less than 0.025 and p less than 0.01, respectively), but decreased thereafter with higher doses of T4. At the 600-micrograms dose of T4, CBG concentrations returned to baseline values. We conclude that in the baboon, T4 increases the circulating levels of SBP in a graded fashion, while the effect on CBG is biphasic.

Animals↗

Dynamics of steroid biosynthesis during the luteal-placental shift in rhesus monkeys.

We studied the dynamics of steroid secretion during the luteal-placental shift of early pregnancy in rhesus monkeys. Daily blood samples were obtained from six pregnant rhesus monkeys during the cycle of conception and for the first 44 days of pregnancy to examine the relationships among aromatizable androgens, estrogens, progesterone (P), and CG in the peripheral circulation. To elucidate the biosynthetic mechanisms involved in the changes in hormonal patterns, minces of placentae and corpora lutea (CL) were incubated in vitro with [3H]pregnenolone ([3H]P5) and [3H]androstenedione ([3H]A), and steroid metabolites were isolated and identified by reverse isotope dilution. After a brief rise (corresponding to the approximate time of implantation of the blastocyst), serum P levels declined despite rising serum CG levels and reached a nadir at the time of maximal CG secretion. In contrast, serum androstenedione (A), testosterone (T), estrone (E1), and estradiol (E2) concentrations rose and fell in parallel with CG and reached peak levels near day 24 of pregnancy 2- to 10-fold higher than those during the luteal phase. The CL of early pregnancy produced less than one third as much P from [3H]P5 as did the CL of the cycle, but had a 9-fold greater capacity for estrogen biosynthesis. Total CL aromatase activity did not differ between the nonfertile cycle and early pregnancy. 17-Hydroxylase and C17-20 lyase activities increased in the CL during early pregnancy, since 17-hydroxyprogesterone and A (but not T) syntheses were 3- to 5-fold greater in the CL of early pregnancy than in the CL of the cycle. Although serum E1 and E2 concentrations during early pregnancy were similar, E1 was the predominant estrogen produced from [3H]P5 or [3H] A by luteal tissue in vitro. Placental tissue obtained on days 23-27 of pregnancy produced large amounts of P from [3H]P5, but only trace amounts of estrogens were formed from [3H]A. By day 45 of pregnancy, however, the placenta had acquired substantial amounts of aromatase activity. Neither estrogens nor androgens were formed from [3H]P5 by the placenta.(ABSTRACT TRUNCATED AT 400 WORDS)

Androgens↗

A pharmacodynamic comparison of human urinary follicle-stimulating hormone and human menopausal gonadotropin in normal women and polycystic ovary syndrome.

We performed a pharmacodynamic comparison of human urinary follicle-stimulating hormone (hFSH) and human menopausal gonadotropin (hMG) to characterize differences in the bioavailability of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), as well as to compare estrogen responses in normal women and those with polycystic ovary syndrome (PCOS). Ten women with PCOS and ten normal ovulatory controls were randomized to receive a single dose (2 ampules) of either hFSH or hMG. Serum LH decreased significantly following hFSH with responses occurring earlier in controls (24.5 +/- 10.9% after 30 minutes) than in PCOS patients (27.3 +/- 7.5% after 18 hours). After hMG, LH increased only in controls (33.8 +/- 16.3%). An FSH increment following hFSH was observed in both PCOS patients (54.7 +/- 24.8%) and controls (74.6 +/- 36.8%), with peak responses at 6 and 4 hours, respectively. However, after hMG, FSH increased only in controls. The LH/FSH ratio after hFSH decreased, with the nadir at 18 hours (1.438 +/- 0.183) being similar to baseline LH/FSH ratios of controls (1.433 +/- 0.341). Serum estradiol (E2) increased following hMG, with peak responses after 18 hours, in both PCOS patients (75.4 +/- 28.6%) and controls (88.5 +/- 32.5%). The peak E2 response to hFSH was observed to be earlier in PCOS patients (147 +/- 34%), occurring after 12 hours, compared with controls (58 +/- 29% after 18 hours).

Adult↗

Rapid measurement of urinary pregnanediol glucuronide to diagnose ectopic pregnancy.

We investigated the ability of a single, random, urinary pregnanediol-3 alpha-glucuronide level to differentiate early intrauterine from ectopic pregnancy. Thirty-four patients with intrauterine gestations were compared with 60 patients with ectopic pregnancies. Urinary pregnanediol-3 alpha-glucuronide was measured by radioimmunoassay and enzyme immunoassay. Compared with intrauterine gestations, results demonstrate that urinary pregnanediol-3 alpha-glucuronide is significantly depressed in ectopic pregnancies: 24.5 +/- 2.2 versus 4.8 +/- 0.7 micrograms/ml (p = 0.0001). Urinary pregnanediol-3 alpha-glucuronide levels obtained by conventional radioimmunoassay correlated closely with values measured in minutes with enzyme immunoassay (r = 0.95, p = 0.0001), and with serum progesterone (r = 0.74, p = 0.0001). Urinary pregnanediol-3 alpha-glucuronide measured by enzyme immunoassay exhibited predictive values for detecting ectopic gestations comparable with random serum progesterone or serum beta-human chorionic gonadotropin values. We conclude that ectopic gestations demonstrate a reduced level of urinary pregnanediol-3 alpha-glucuronide (55/60 cases) detectable with a rapid enzyme immunoassay, which makes this assay a practical screening test in early pregnancy.

Chorionic Gonadotropin↗