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E Gentzschein

Publications and source records attributed to E Gentzschein.

17 recordsLinked to original sources
PubMed2001

Prostate cancer risk and serum levels of insulin and leptin: a population-based study.

BACKGROUND: In a previous study of Chinese men, we found that men with a higher waist-to-hip ratio (WHR) have a higher prostate cancer risk. Because leptin and insulin are related to body fat distribution, we examined whether leptin and insulin were associated with prostate cancer risk. METHODS: Blood samples were collected from 128 case patients with incident prostate cancer and from 306 healthy control subjects randomly selected from residents of Shanghai, CHINA: Epidemiologic information and anthropometric measurements were collected in personal interviews. Serum leptin, insulin, and sex hormone levels were measured by radioimmunoassay, and insulin-like growth factor-I (IGF-I) was measured by enzyme-linked immunosorbent assay. Multiple logistic regression analyses were used to estimate odds ratios for prostate cancer in relation to serum insulin and leptin levels. All statistical tests were two-sided. RESULTS: After adjustment for body mass index, WHR, IGF-I, and sex hormone levels, higher serum insulin levels were associated with a statistically significantly elevated risk of prostate cancer (P<.001). Men in the highest tertile of insulin levels had a 2.56-fold (95% confidence interval [CI] = 1.38 to 4.75) risk of prostate cancer compared with men in the lowest tertile. Regardless of the tertile level of WHR, higher serum insulin levels were associated with an increased risk of prostate cancer: Men in the highest tertiles of WHR (>0.900) and insulin (>8.83 microU/mL) had 8.55 times (95% CI = 2.80 to 26.10) the prostate cancer risk of men in the lowest tertiles of both, and those in the lowest tertile of WHR (<0.873) and highest tertile of insulin had 4.30 times (95% CI = 1.17 to 15.70) the risk. By contrast, the association between leptin levels and prostate cancer risk was not statistically significant. CONCLUSION: Our results suggest that serum insulin levels may influence the risk of prostate cancer in Chinese men. Further research, especially prospective studies, is needed to confirm these findings in high-risk populations and to clarify the underlying mechanisms involved.

Age Factors↗
PubMed2001

Do urinary estrogen metabolites reflect the differences in breast cancer risk between Singapore Chinese and United States African-American and white women?

Breast cancer risk is substantially lower in Singapore than in women from the United STATES: Part of the risk discrepancy is probably explained by differences in the production of endogenous estrogens, but differences in the pathway by which estrogen is metabolized may also play a role. We undertook a study to determine whether the ratio of urinary 2-hydroxyestrone (2OHE(1)):16alpha-hydroxyestrone (16alpha-OHE(1)) was higher in Singapore Chinese than in a group of United States (predominantly African-American) women living in Los ANGELES: We also wanted to determine whether any difference in estrogen metabolite ratio between these two groups of women was greater than that in estrone (E(1)), estradiol (E(2)) and estriol (E(3)). The participants in this study were randomly selected healthy, non-estrogen using women participating in the Singapore Chinese Health Study (n = 67) or the Hawaii/Los Angeles Multiethnic Cohort Study (n = 58). After adjusting for age and age at menopause, mean urinary 2-OHE(1) was only 23% (P = 0.03) higher in Singapore Chinese than in United States women, and there were no statistically significant differences in 16alpha-OHE(1) levels or in the ratio of 2-OHE(1):16alpha-OHE(1) between the two groups. The adjusted mean 2-OHE(1):16alpha-OHE(1) ratio was 1.63 in Singapore Chinese and 1.48 in United States women (P = 0.41). In contrast, the adjusted mean values of E1, E2, and E3 were 162% (P < 0.0001), 152% (P < 0.0001), and 92% (P = 0.0009) higher, respectively, in United States women than in Singapore Chinese women. Our study suggests that urinary E1, E2, and E3 reflect the differences in breast cancer risk between Singapore Chinese and United States women to a stronger degree than the estrogen metabolites 2OHE(1) and 16alpha-OHE(1) or the ratio of 2OHE(1):16alpha-OHE(1.)

Aged↗
PubMed1999

Urinary 2-hydroxyestrone/16alpha-hydroxyestrone ratio and risk of breast cancer in postmenopausal women.

BACKGROUND: It has been suggested that women who metabolize a larger proportion of their endogenous estrogen via the 16alpha-hydroxylation pathway may be at elevated risk of breast cancer compared with women who metabolize proportionally more estrogen via the 2-hydroxylation pathway. However, the supporting epidemiologic data are scant. Consequently, we compared the ratio of urinary 2-hydroxyestrone (2-OHE1) to 16alphahydroxyestrone (16alpha-OHE1) in postmenopausal women with breast cancer and in healthy control subjects. METHODS: Estrogen metabolites were measured in urine samples obtained from white women who had participated in a previous population-based, breast cancer case-control study at our institution. All P values are from two-sided tests. RESULTS: All of the urinary estrogens measured, with the exception of estriol, were higher in the 66 case patients than in the 76 control subjects. The mean value of urinary 2-OHE1 in case patients was 13.8% (P = .20) higher than that in control subjects, 16alpha-OHE1 was 12.1% (P = .23) higher, estrone was 20.9% higher (P = .14), and 17beta-estradiol was 12.0% higher (P = .36). The ratio of 2-OHE1 to 16alpha-OHE1 was 1.1% higher in the patients (P = .84), contrary to the hypothesis. Compared with women in the lowest third of the values for the ratio of urinary 2-OHE1 to 16alpha-OHE1, women in the highest third were at a nonstatistically significantly increased risk of breast cancer (odds ratio = 1.13; 95% confidence interval = 0.46-2.78), again contrary to the hypothesis. CONCLUSION: This study does not support the hypothesis that the ratio of the two hydroxylated metabolites (2-OHE1/16alpha-OHE1) is an important risk factor for breast cancer.

Aged↗
PubMed1999

Effect of oral contraceptives containing 20 and 35 micrograms ethinyl estradiol on urinary prostacyclin and thromboxane metabolite levels in smokers and nonsmokers.

The interaction between smoking and oral contraceptive (OC) use with respect to thrombogenesis was investigated by studying the effects of OC and smoking on urinary prostacyclin (PGI2) and thromboxane A2 (TxA2) metabolite levels in smokers and nonsmokers. Sixty healthy women, aged 19-32 years, who were not taking any hormonal treatment for at least 3 months before initiating the study, were divided into three equal groups: OC users who smoked (N = 20), OC users who did not smoke (N = 20), and a control group of 10 smokers and 10 nonsmokers. Each OC treatment group was randomized to receive either norethindrone (NET) acetate (1 mg)/ethinyl estradiol (EE2) (35 micrograms) (N = 10) or NET acetate (1 mg)/EE2 (20 micrograms) (N = 10) daily for 3 months. Overnight urine collections and fasting blood samples were obtained at baseline and at the end of the 3-month study. Serum levels of NET and EE2, as well as urinary levels of cotinine and the stable metabolites of PGI2 and TxA2, namely 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane (TxB2), respectively, were measured by specific immunoassays. Analysis of pre- to posttreatment changes in mean urinary 6-keto-PGF1 alpha and TxB2 levels for each subgroup, as determined by smoking status and EE2 dose, showed no statistically significant differences. Also, no significant differences were found in each subgroup with respect to changes in the 6-keto-PGF1 alpha/TxB2 ratios. Large intersubject variability in urinary 6-keto-PGF1 alpha and TxB2 levels were observed in all subgroups. The results of this study indicate that both low-estrogen-dose compounds, when used by smokers or nonsmokers, did not significantly alter the ratio of PGI2 to TXA2 metabolites, compared with pretreatment. However, the small number of subjects and the large intersubject variability in this study make it difficult to determine if there is a significant difference between the 20- and 30-microgram EE2 doses.

6-Ketoprostaglandin F1 alpha↗
PubMed1997

Endothelin levels decrease after oral and nonoral estrogen in postmenopausal women with increased cardiovascular risk factors.

OBJECTIVE: To establish levels of plasma endothelin-1 in postmenopausal women with increased CV risk as compared with healthy premenopausal women and to measure the effects of different forms of estrogen replacement on plasma endothelin-1. DESIGN: Prospective randomized study. SETTING: University of Southern California Medical Center. PATIENT(S): We studied 18 postmenopausal women (mean age 53.4 +/- 4.9 years) with total cholesterol levels > 240 mg/dL divided into those with and without hypertension as well as in 10 healthy premenopausal women. INTERVENTION(S): The postmenopausal women were randomized to receive oral estrone sulfate, transdermal E2, or placebo for 30 days. MAIN OUTCOME MEASURE(S): We measured the endothelin-1 levels and total cholesterol at baseline and after 30 days of estrogen treatment. RESULT(S): In the postmenopausal women, endothelin-1 was higher (4.58 +/- 0.46 pg/mL) compared with premenopausal levels (2.80 +/- 0.46 pg/mL). In hypertensive postmenopausal women, endothelin-1 was 5.56 +/- 0.44 pg/mL. After estrogen, plasma endothelin-1 values decreased from 5.38 +/- 0.66 to 4.82 +/- 0.9 pg/mL with oral estrone sulfate, 4.84 +/- 0.25 to 4.54 +/- 0.49 pg/mL with transdermal E2, and did not change after placebo 4.76 +/- 0.71 to 4.81 +/- 0.46 pg/mL. In evaluating hypertensive women alone with estrogen therapy, plasma endothelin-1 showed the greatest decrement from 5.39 +/- 0.49 to 4.4 +/- 0.59 pg/mL (18.4%). The decrease in endothelin-1 with estrogen, which was statistically significant for the entire group, did appear to be influenced by the route of administration. Baseline plasma endothelin-1 levels were correlated positively to plasma cholesterol levels with a correlation coefficient of 0.632. CONCLUSION(S): These data provide another potential mechanism explaining the cardioprotective effects of hormone replacement therapy.

Administration, Cutaneous↗
PubMed1997

A pilot study of urinary estrogen metabolites (16alpha-OHE1 and 2-OHE1) in postmenopausal women with and without breast cancer.

The two main pathways for metabolizing estrogen are via 16alpha-hydroxylation and 2-hydroxylation. The 16alpha-hydroxy metabolites are biologically active; the 2-hydroxy metabolites are not. It is suggested that women who metabolize a larger proportion of their endogenous estrogen via the 16alpha-hydroxy pathway may be at significantly elevated risk of breast cancer compared with women who metabolize proportionally more estrogen via the 2-hydroxy pathway. In particular, it is suggested that the ratio of urinary 2-hydroxyestrone (2-OHE1) to 16alpha-hydroxyestrone (16alpha-OHE1) is an index of reduced breast cancer risk. This pilot study compared this ratio in postmenopausal women diagnosed with breast cancer to those of healthy controls. Urinary concentrations of estrone (E1), 17beta-estradiol (E2) and estriol (E3) were also quantified. White women who were subjects in a previous breast cancer case-control study at our institution were eligible for inclusion. All participants provided a sample of their first morning urine. The results from the first 25 cases and 23 controls are presented here. The ratio of 2-OHE1 to 16alpha-OHE1 was 12% lower in the cases (p=0.58). However, urinary E1 was 30% higher (p=0.10), E2 was 58% higher (p=0.07), E3 was 15% higher (p=0.48), and the sum of E1, E2, and E3 was 22% higher (p=0.16) in the cases. These preliminary results do not support the hypothesis that the ratio of the two hydroxylation metabolites (2-OHE1/16alpha-OHE1) is an important risk factor for breast cancer or that it is a better predictor of breast cancer risk than levels of E1, E2 and E3 measured in urine.

Breast Neoplasms↗
PubMed1997

Urinary progesterone and pregnanediol. Use for monitoring progesterone treatment.

OBJECTIVE: To compare progesterone (P) and pregnanediol glucuronide (PDG) levels in urine with respect to their potential use for monitoring luteal activity and P treatment. STUDY DESIGN: Two different experiments were carried out. In the first experiment, each of seven normal, ovulatory women collected first morning urines daily throughout an entire menstrual cycle. The day of ovulation was determined by transvaginal ultrasound scanning. P, PDG, estrone glucuronide, luteinizing hormone and creatinine were measured in each urine specimen. In the second experiment, each of three normal, ovulatory women was given a single oral dose of 200 mg of micronized P and, 2 days later, a single intramuscular injection of 25 mg of P during days 2-5 of the cycle. Blood and urine were collected prior to each treatment and 1, 4, 8, 12 and 24 hours after treatment. P was measured in both serum and urine; PDG was quantified only in urine. RESULTS: The mean initial rises and peak days, as well as the patterns of urinary excretion of P and PDG during the menstrual cycles, were similar; however, the variability of PDG was much greater. Concentrations of PDG were 1,000-4,000 times greater than those of P. A significant correlation was observed between urinary P and PDG. Following either intramuscular or oral P treatment, serum P levels rose rapidly and reached peak levels (7.0-11.8 ng/mL) by one hour. In contrast, both urinary P and PDG peaked considerably later (4-12 hours). Twenty-four hours after intramuscular treatment, serum and urinary P and urinary PDG were still elevated. Following oral treatment the levels of these compounds decreased after peaking and were 10- to 20- fold lower at 24 hours. Also, after oral P treatment, urinary PDG levels were considerably higher and more variable as compared to urinary P levels. CONCLUSION: Urinary P appears to be as good a clinical marker of luteal activity and therapeutic P administration as PDG and may be measured in place of this metabolite. There appears to be greater variability in urinary PDG as compared to urinary P when P is administered.

Adult↗
PubMed1996

Biologic effects of 17 alpha-dihydroequilin sulfate.

OBJECTIVE: To determine the independent biologic effects of 17 alpha-dihydroequilin sulfate. DESIGN: Prospective randomized study. SETTING: University of Southern California Medical Center. PATIENTS(S): Twenty-one postmenopausal women, mean age 50 +/- 2 (+/-SEM) years, and mean body mass index 27 +/- 2. INTERVENTION(S): Women were randomized to receive daily oral doses of either 1.25 mg of estrone sulfate (E1S), 0.2 mg of 17 alpha-dihydroequilin sulfate, or a combination. Three blood and urine samples were obtained before and after 30 and 90 days of treatment. RESULT(S): After 30 and 90 days of treatment, E1S alone increased sex hormone-binding globulin (SHBG) levels significantly, 19.7% +/- 6.0% and 61.3% +/- 13.0%, whereas 17 alpha-dihydroequilin sulfate reduced SHBG levels, 20.8% +/- 68% and 12.4% +/- 7.5%, respectively. Nevertheless, the combination of E1S and 17 alpha-dihydroequilin sulfate significantly increased SHBG levels, 103% +/- 27.9% and 98.2% +/- 19.1%, compared with baseline at 30 and 90 days. Fewer changes were evident with corticosteroid-binding globulin (CBG). After 90 days of treatment, CBG levels significantly increased 30.9% +/- 5.5% with E1S, decreased by 7.2% +/- 5.0% with 17 alpha-dihydroequilin sulfate, and, with the combination, significantly increased by 10.5% +/- 2.4% compared with baseline. Changes in lipids and lipoproteins were more variable. However, high-density-lipoprotein cholesterol increased significantly with E1S at 30 and 90 days compared with baseline, 96.5% +/- 39% and 91.5% +/- 22.6%, and with the combination increased 66.4% +/- 13.3% and 79.2% +/- 24.4%, respectively. Fewer changes were evident with 17 alpha-dihydroequilin sulfate alone, decreasing 4.4% +/- 22% and 2.6% +/- 21.3%. Urinary ratios of bone collagen equivalents-creatinine and calcium-creatinine decreased in all three groups. However, the combination group resulted in a significantly greater percentage decrease in bone collagen equivalents-creatinine than with E1S alone. CONCLUSIONS(S): 17 alpha-Dihydroequilin sulfate could modify some of the first-pass effects of conjugated equine estrogens and act synergistically with other conjugated equine estrogens to reduce bone resorption.

Calcium↗
PubMed1995

Substrate dependency of C19 conjugates in hirsute hyperandrogenic women and the influence of adrenal androgen.

Serum C19 conjugates, specifically 3 alpha-androstanediol glucuronide (3 alpha G), reflect peripheral androgen action through the action of 5 alpha-reductase activity. The origin of 5 alpha-reduced C19 conjugates has been controversial and it has been suggested that they are derived primarily from adrenal androgens. We examined concentrations of 3 alpha G, 3 alpha-androstanediol sulphate (3 alpha S), androsterone glucuronide (AoG) and androsterone sulphate (AoS) in 40 hirsute hyperandrogenic women. These patients were divided into four groups based upon individual, combined or normal concentrations of the adrenal androgens dehydroepiandrosterone (DHEAS) and 11 beta-hydroxy-androstenedione. Testosterone, unbound testosterone and androstenedione were similar in these groups. Serum 3 alpha G was equally high in all groups and was correlated significantly with hirsutism, while the other conjugates were not. Androsterone glucuronide was raised in all groups but was higher in patients with raised DHEAS. Serum 3 alpha S was raised in all groups and was higher where both adrenal androgens were raised. Serum AoS was highly correlated with DHEAS. Serum 3 alpha G was correlated with unbound testosterone and androstenedione but not with the adrenal androgens. The glucuronide conjugates were correlated with one another as were the sulphate conjugates but glucuronides and sulphates were not correlated. These data confirm ovarian and adrenal dependency of C19 conjugates. Serum 3 alpha G appears to reflect hirsutism most accurately and is least dependent on adrenal androgens in patients with mixed hyperandrogenism.

Adrenal Glands↗
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↗
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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1987

Production of 3 alpha-androstanediol glucuronide in human genital skin.

3 alpha-Androstanediol glucuronide (3 alpha diol-G) is produced extrasplanchnically and is a good clinical marker of androgen action in peripheral tissues. However, the direct formation of androgen glucuronides in peripheral sites such as skin has not been determined in man. Genital skin from 21 premenopausal women and 8 men and foreskin from 6 neonates were incubated with either [14C]testosterone [14C]dihydrotestosterone (DHT) to determine the production of DHT glucuronide and 3 alpha diol-G in skin. After hydrolysis of incubation medium with glucuronidase, followed by extraction and sequential chromatography, constant 3H to 14C ratios of 3 alpha diol confirmed the production of DHT glucuronide and 3 alpha diol-g. The conversion of DHT to 3 alpha diol-G was higher than the conversion from testosterone (P less than 0.05), and conversion was higher in men than in women. These data provide evidence for the direct formation of C19 steroid glucuronides by human skin.

Adult↗
PubMed1980

Clinical and endocrinologic study of continuous levonorgestrel administration from subcutaneous solid polydimethylsiloxane rods.

Three solid polydimethylsiloxane (Silastic) rods containing levonorgestrel were inserted into the subcutaneous tissue of the volar aspect of the forearm of 8 women. Serum samples were drawn three times a week for 2 months and weekly thereafter for 2 years in 3 of the subjects. The other subjects had serum drawn during the twelfth and last treatment months. Levonorgestrel, estradiol and progesterone were measured in all samples. The subject kept a bleeding record. In comparison to an earlier clinical trial in which 6 hollow capsules of Silastic filled with levonorgestrel were used, the 3 solid levonorgestrel-containing rods provided higher serum levels of levonorgestrel, fewer serum estradiol peaks, only a single episode of ovulation and better bleeding performance.

Adult↗
PubMedDate not supplied

Plasma prostaglandin E(2) metabolite levels during labor induction with a sustained-release prostaglandin E(2) vaginal insert.

OBJECTIVE: To measure prostaglandin E(2) levels during labor induction with a sustained-release vaginal polymer insert (prostaglandin E(2) insert) and to determine whether Bishop score change correlated with tachysystole. METHODS: Twelve primiparas and 12 multiparas were treated with a 0.3 mg per hour sustained-release polymer vaginal prostaglandin E(2) insert for up to 24 hours. Bishop score was assessed at start and end of therapy, and serum samples were collected at 4-hour intervals. Prostaglandin E(2) metabolite (PGEM) levels were measured by specific enzyme immunoassay. RESULTS: Exposure averaged 13.5 +/- 7.2 hours. Four patients (16.7%, three nulliparas) had tachysystole. Mean PGEM levels increased from 187 +/- 42 pg/mL at baseline to 548 +/- 110 pg/mL at 12 hours (P <.05) and remained relatively stable thereafter. Nulliparas with Bishop score changes of four points or more had the highest increase, with average peak levels of 985 +/- 109 pg/mL, compared with 452 +/- 58 pg/mL for all others (P <.001). Patients with tachysystole had higher 4-hour (P <.01) and overall (P <.04) increases in PGEM level. Removal of the insert led to an average decrease of 335 pg/mL in PGEM levels (P <.01). The decrease correlated with the PGEM level measured before removal (r =.94, P <.0001) and the maximum PGEM increase from baseline (r =.94, P <.0001). The mean mixed venous cord PGEM level was 409 +/- 375 pg/mL. CONCLUSION: Administration of the prostaglandin E(2) insert led to a sustained increase in circulating PGEM levels in women who had labor induction. Peak PGEM levels correlated with Bishop score improvement. Rapid increases in prostaglandin E(2) levels might cause tachysystole.

Administration, Intravaginal↗