Temporal changes in cervical mucus after insertion of the levonorgestrel-releasing intrauterine system.

Background: The major contraceptive action of the levonorgestrel-releasing intrauterine system (LNG-IUS) is cervical mucus (CM) thickening, which prevents sperm penetration. No study to date has examined the temporal relationship between the insertion of the LNG-IUS and changes in CM quality and sperm penetration.

Study Design: Participants were enrolled in a clinically descriptive study to compare the quality of CM and three parameters of sperm penetration prior to insertion of the LNG-IUS and on Days 1, 3 and 5 after insertion.

Sex steroid hormone levels in breast adipose tissue and serum in postmenopausal women.

Elevated levels of circulating estrogens and androgens are linked to higher breast cancer risk among postmenopausal women; however, little is known about hormone levels within the breast. Hormone concentrations within the breast may not be reflected in the blood and are likely important contributors to breast carcinogenesis. We used a previously validated method to measure levels of estrone, estradiol, androstenedione, and testosterone in adipose tissue removed as part of breast excisions performed for cancer in 100 postmenopausal women (69 ER/PR +/+ and 31 ER/PR -/-) participating in a breast cancer case-control study.

Estrogen levels in nipple aspirate fluid and serum during a randomized soy trial.

Background: On the basis of hypothesized protective effect, we examined the effect of soy foods on estrogens in nipple aspirate fluid (NAF) and serum, possible indicators of breast cancer risk.

Methods: In a crossover design, we randomized 96 women who produced 10 μL or more NAF to a high- or low-soy diet for 6 months. During the high-soy diet, participants consumed 2 soy servings of soy milk, tofu, or soy nuts (∼50 mg of isoflavones per day); during the low-soy diet, they maintained their usual diet.

Sex differences in β-amyloid accumulation in 3xTg-AD mice: role of neonatal sex steroid hormone exposure.

The risk of Alzheimer's disease (AD) is higher in women than in men, a sex difference that likely results from the effects of sex steroid hormones. To investigate this relationship, we first compared progression of β-amyloid (Aβ) pathology in male and female triple transgenic (3xTg-AD) mice. We found that female 3xTg-AD mice exhibit significantly greater Aβ burden and larger behavioral deficits than age-matched males.

Measurement of sex steroid hormones in breast adipocytes: methods and implications.

Background: The lack of validated methods for measuring sex steroid hormones in breast tissue has limited our knowledge of their role in the development of breast cancer. We explored the feasibility of measuring hormones in breast adipocytes for epidemiologic and clinical studies by refining an existing assay procedure and assessing the reliability of hormone measurements using the modified assay. This report presents the reproducibility of measurements of androstenedione (A), testosterone (T), estrone (E(1)), and estradiol (E(2)), using breast adipose tissue samples obtained from women undergoing surgical resection for a variety of pathologic conditions.

Formation of ethinyl estradiol in women during treatment with norethindrone acetate.

Context: The significance of the conversion of norethindrone acetate (NET-A), a commonly prescribed, synthetic, oral progestogen, to ethinyl estradiol (EE(2)) is controversial.

Objective: We sought to determine accurately the extent to which NET-A may be converted to EE(2), and if so, whether circulating levels of EE(2) would be of clinical significance. DESIGN, SUBJECTS, AND INTERVENTIONS: We administered NET-A 10, 20, or 40 mg once daily for 7 d to 20 regularly menstruating premenopausal women and measured NET-A and EE(2) levels before drug intake; at 1, 2, 4, 8, and 24 h after the first dose; and 2 h after the seventh dose.

Locus-wide chromatin remodeling and enhanced androgen receptor-mediated transcription in recurrent prostate tumor cells.

Prostate cancers (PCas) become resistant to hormone withdrawal through increased androgen receptor (AR) signaling. Here we show increased AR-mediated transcription efficiency in PCa cells that have acquired the ability to grow in low concentrations of androgen. Compared to androgen-dependent PCa cells, these cells showed increased activity of transiently transfected reporters and increased mRNA synthesis relative to levels of AR occupancy of the prostate-specific antigen (PSA) gene.

Long-term, low-dose lead exposure alters the gonadotropin-releasing hormone system in the male rat.

Lead is a male reproductive toxicant. Data suggest that rats dosed with relatively high levels of lead acetate for short periods of time induced changes in the hypothalamic gonadotropin-releasing hormone (GnRH) at the molecular level, but these changes were attenuated with increased concentration of exposure. The current study evaluated whether exposure to low levels of lead acetate over longer periods of time would produce a similar pattern of adaptation to toxicity at the molecular and biologic levels.

Urinary 2-hydroxyestrone/16alpha-hydroxyestrone ratio and family history of breast cancer in premenopausal women.

It has been hypothesized that the ratio of urinary 2-hydroxyestrone to 16alpha-hydroxyestrone (2-OHE1/16alpha-OHE1 represents a biomarker for breast cancer risk; the lower the ratio the higher the risk. We obtained early morning urine samples from 70 'high risk' premenopausal women who had a first degree family history of breast cancer and 27 'low risk' women with no such history. Five estrogen metabolites in urine were determined: 2-OHE1, 16alpha-OHE1, estrone (E1), estradiol (E2), and estriol (E3) conjugates.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.