Biomedical subjects

F Z Stanczyk

Publications and source records attributed to F Z Stanczyk.

At least 73 records · Page 4Linked to original sources

PubMed1997

Cardioprotective effects of individual conjugated equine estrogens through their possible modulation of insulin resistance and oxidation of low-density lipoprotein.

OBJECTIVE: To examine the independent effects on insulin sensitivity and antioxidative activity of the three most prevalent constituents in Premarin (Wyeth-Ayerst Laboratories, Philadelphia, PA): estrone sulfate (E1S), 50%; equilin sulfate (EqS), 25%, and 17 alpha-dihydroequilin sulfate (17 alpha-ES), 15%. DESIGN: Prospective randomized cross-over study. SETTING: University of Southern California Medical Center. PATIENT(S): Eight healthy postmenopausal women, mean age 53 +/- 2 years, and mean body mass index, 26 +/- 2 kg/m2, were enrolled. INTERVENTION(S): Each woman received, in randomized succession, daily oral doses of 17 alpha-ES (0.2 mg), E1S (0.625 mg), and EqS (0.3 mg) for 30 days. MAIN OUTCOME MEASURE(S): Oxidation of low-density lipoprotein (LDL) by negatively charged LDL (LDL-) and lag phase duration and measured the plasma glucose disappearance after insulin administration (K(itt)). RESULT(S): All three estrogen preparations demonstrated antioxidant effects with E1S demonstrating the most significant changes, followed by EqS and 17 alpha-ES. Using E1S, LDL-levels decreased from a baseline of 3.91 +/- 0.9 to 2.05 +/- 0.32 mg/dL and the lag time increased from 24.5 +/- 6.0 to 87.8 +/- 11.8 minutes. Changes in insulin tolerance tests revealed improved insulin action with the various estrogens. With EqS, K(itt) increased from 3.1% +/- 0.3% to 4.3% +/- 0.3% glucose/min, was intermediate with E1S and was least with 17 alpha-ES. CONCLUSION(S): All three conjugated equine estrogens demonstrated antioxidant activity. Also, some improved insulin action was demonstrated. To our knowledge, this is the first in vivo study to examine the effects of these components which may help explain, in part, some of the cardioprotective properties ascribed to Premarin.

Adult↗

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

Endocrine abnormalities in ovulatory women with polycystic ovaries on ultrasound.

Polycystic-appearing ovaries (PAO) on ultrasound have been described in a variety of endocrinopathies and also occur in ovulatory women. By some investigators this is merely referred to as 'PCO' (polycystic ovaries). Although there is controversy in this regard, we do not consider women with PAO/PCO who have no known endocrine disturbance to have polycystic ovary syndrome (PCOS) and therefore prefer not to use the term 'PCO' which is often equated with PCOS. We studied 15 ovulatory women with normal-appearing (NAO) ovaries on ultrasound and 15 matched ovulatory women with PAO/PCO. Compared to ovulatory women, 25 other women were studied who were considered to have PCOS. Of these, 15 were overweight and 10 were of normal weight. All the PCOS women had serum concentrations of luteinizing hormone (LH), testosterone, unbound testosterone, androstenedione and dihydroepiandrosterone sulphate (DHEAS) which were significantly higher (P < 0.01) than values in the normal women, regardless of ovarian morphology. These values were similar in the two groups of ovulatory women with NAO and PAO/PCO. Fasting insulin was elevated in women with PCOS with increased body weight (P < 0.01) and was higher than in ovulatory women with NAO and PAO/PCO and than in women of normal weight with PCOS. Serum insulin-like growth factor (IGF)-I and binding protein (BP)-3 were similar in all groups but serum IGFBP-1 was significantly (P < 0.01) lower in those women with PCOS with increased body weight, compared to all other groups. Compared to values in ovulatory women with NAO, serum IGFBP-1 was also significantly (P < 0.05) lower in women with PAO/PCO and those women with PCOS of normal weight. These lower values were similar in women with PAO/PCO and in normal weight women with PCOS. On an individual basis, an elevation of at least one serum androgen value was found in 33% of women with PAO/PCO. These data confirm that increased body weight accentuates the metabolic alterations in PCOS, but suggest that subtle endocrine disturbances, similar to those that are found in PCOS, may be uncovered in up to a third of ovulatory women with PAO/PCO. It appears that a disturbance of the IGF/IGFBP-1 axis is common and apparently closely associated with alterations in ovarian morphology.

Adult↗

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

5 alpha-reductase activity and prostate cancer: a case-control study using stored sera.

We report a nested case-control study of serum biomarkers of 5 alpha-reductase activity and the incidence of prostate cancer. From a cohort of more than 125,000 members of the Kaiser Permanente Medical Care Program who underwent multiphasic health examinations during 1964-1971, we selected 106 incident prostate cancer cases. A control was pair matched to each case on age, date of serum sampling, and clinic location. Serum levels of total testosterone, free testosterone, androsterone glucuronide, and 5 alpha-androstane-3 alpha,17 beta androstanediol glucuronide (3 alpha-diol G) were measured on the stored samples and scored as quartiles. Potential confounders included alcohol, smoking, and body mass index. The adjusted odds ratios and 95% confidence intervals for a one quartile score increase were 1.00 (0.75-1.34) for total testosterone, 1.14 (0.86-1.50) for free testosterone, 1.13 (0.84-1.53) for androsterone glucuronide, and 1.16 (0.86-1.56) for 3 alpha-diol G. A limitation of this study is that there are two different 5 alpha-reductase isoenzymes, only one of which is expressed in high levels within the prostate, yet both of which may affect serum biomarkers. Since the two isoenzymes are encoded on different chromosomes, variation in one would act as an independent source of measurement error in any analysis of serum biomarker effects of the other. Consequently, the odds ratios may be underestimated and the study, although negative, cannot exclude the previously hypothesized possibility that a positive relationship between intraprostatic 5 alpha-reductase activity and prostate cancer may exist. A clinical trial to test this hypothesis is under way.

Aged↗

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↗

PubMed1997

Relationship of serum dehydroepiandrosterone (DHEA), DHEA sulfate, and 5-androstene-3 beta, 17 beta-diol to risk of breast cancer in postmenopausal women.

Laboratory evidence suggests a role for dehydroepiandrosterone (DHEA) and its metabolite 5-androstene-3 beta, 17 beta-diol (ADIOL) in mammary tumor growth. Serum DHEA also has been related to breast cancer in postmenopausal women, but the relationship of ADIOL to risk has not been evaluated previously. To assess the relationship of serum DHEA, its sulfate (DHEAS), and ADIOL with breast cancer risk in postmenopausal women, we conducted a prospective nested case-control study using serum from the Columbia, MO Breast Cancer Serum Bank. Cases included 71 healthy postmenopausal volunteers not taking replacement estrogens when they donated blood and who were diagnosed with breast cancer up to 10 years later (median, 2.9 years). Two randomly selected controls, who also were postmenopausal and not taking estrogens, were matched to each case on exact age, date (+/-1 year), and time (+/-2 h) of blood collection. Significant (trend P = 0.02) gradients of increasing risk of breast cancer were observed for increasing concentrations of DHEA and ADIOL, and women whose serum levels of these hormones were in the highest quartiles were at a significantly elevated risk compared to those in the lowest; their risk ratios were 4.0 [95% confidence interval (CI), 1.3-11.8) and 3.0 (95% CI, 1.0-8.6), respectively. The relationship of DHEAS to breast cancer was less consistent, but women whose serum DHEAS concentration was in the highest quartile also exhibited a significantly elevated risk ratio of 2.8 (95% CI, 1.1-7.4). Results of this prospective study support a role for the adrenal androgens, DHEA, DHEAS, and ADIOL, in the etiology of breast cancer.

Aged↗

PubMed1997

Androgens in serum and the risk of prostate cancer: a nested case-control study from the Janus serum bank in Norway.

We tested the hypothesis that serum levels of testosterone (T), dihydrotestosterone (DHT), and the DHT metabolite 3 alpha,17 beta-androstanediol glucuronide are positively associated with the risk of prostate cancer. This nested case-control study was based on the cohort of men who donated blood to the Janus serum bank at Oslo University Hospital (Oslo, Norway) between 1973 and 1994. Cancer incidence was ascertained through linkage with the Norwegian Cancer Registry. The study included sera from 59 men who developed prostate cancer (cases) subsequent to blood donation and 180 men who were free of any diagnosed cancer (controls) in 1994 and were of similar age (+/- 1 year) and had similar blood storage time (+/- 6 months) to the cases. Neither T, DHT, nor the ratio T:DHT was associated with risk of developing prostate cancer. Compared to the bottom quartile, the odds ratio (OR) associated with the top quartile of T was 0.83 [95% confidence interval (CI), 0.36-1.93]; the OR for the top (compared to the bottom) quartile of DHT was 0.83 (95% CI, 0.36-1.94), and the equivalent OR for T:DHT was 1.31 (95% CI, 0.58-2.97). Similarly, 3 alpha,17 beta-androstanediol glucuronide showed no association with prostate cancer risk; the OR for the top (compared to the bottom) quartile was 1.10 (95% CI, 0.41-2.90). These results showed no association, positive or negative, between androgens measured in serum and the subsequent risk of developing prostate cancer.

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↗

PubMed1996

Serum androgens and prostate cancer.

It is suspected that male hormones are associated with the risk of prostate cancer. To test this hypothesis, we conducted a nested case-control study in a cohort of 6860 Japanese-American men examined from 1971 to 1975. At the time of examination, a single blood specimen was obtained, and the serum was frozen. After a surveillance period of more than 20 years, 141 tissue-confirmed incident cases of prostate cancer were identified, and their stored sera and those of 141 matched controls were assayed for total testosterone, free testosterone, dihydrotestosterone, 3-alpha-androstanediol glucuronide, androsterone glucuronide, and androstenedione. Odds ratios for prostate cancer, based on quartiles of serum hormone levels, were determined using conditional logistic regression methods. The odds ratios for the highest quartiles were 1.37 (95% confidence interval, 0.73-2.55) for 3-alpha-androstanediol glucuronide and 1.24 (95% confidence interval, 0.62-2.47) for androstenedione, but none of the differences was statistically significant. The results were unremarkable for the other four hormonal measurements. In addition, the patients and controls were compared by hormonal ratios (i.e., total testosterone:dihydrotestosterone), but the results were also unremarkable. The findings of this study indicate that none of these androgens is strongly associated with prostate cancer risk.

Aged↗

PubMed1996

Reproducibility studies and interlaboratory concordance for assays of serum hormone levels: estrone, estradiol, estrone sulfate, and progesterone.

We conducted studies to measure sources of assay variability for estrone, estradiol, estrone sulfate, and progesterone for postmenopausal women (n = 5) and for women in the mid-follicular (n = 5) and mid-luteal (n = 5) phases of the menstrual cycle. A single blood sample from each woman was divided into 2.5-ml aliquots and stored at -70 degrees C, and sets of two aliquots were sent at monthly intervals to each of three laboratories (four for progesterone). Each aliquot was analyzed in duplicate. Thus, within each menstrual category, we were able to estimate the components of variance due to variation among women, variation among aliquots, variation among duplicate measurements, and variation among the 4 analysis days. Using the logarithm of assay measurements, we estimated the percentage of variance attributable to variation among women in each menstrual category, 100 rho, is the estimated intraclass correlation. For each assay, 100 rho exceeded 90% for mid-follicular and mid-luteal women. For postmenopausal women, values of 100 rho exceed 84% for estrone in two laboratories. Values of 100 rho were lower for progesterone in postmenopausal women, although a value of 84% was estimated from one laboratory. These studies indicate that estrogen assays over a period of 3 months permit reliable comparisons among women in a given menstrual category. Progesterone measurements are likewise reliable for women in the mid-follicular and mid-luteal phases but somewhat less satisfactory for postmenopausal women. These assessments of variability pertain only to laboratory techniques and do not allow for secular variation in intra-woman hormone levels. Moreover, although these measurements tend to be reliable enough for making comparisons among women, estimates of coefficients of variation for estrogens are about 10% for mid-follicular and mid-luteal phase women and about 11-20% for postmenopausal women. Coefficients of variation for progesterone are about 10% for mid-luteal, 20% for mid-follicular, and 30% for postmenopausal women.

Analysis of Variance↗

PubMed1995

A cohort study of serum testosterone and hepatocellular carcinoma in Shanghai, China.

A nested case-control study of HCC based on a cohort of 18,244 middle-aged men in Shanghai, China, who had been followed for an average of 5.3 years, was conducted. Our hypothesis dealt with the possible role of testosterone in the etiology of HCC, which shows a minimum of a 2- to 3-fold male excess in all populations world-wide. Seventy-six incident cases of HCC and 410 control subjects drawn from the cohort and individually matched to the cases by age (within 1 year), time of blood sample collection (within 1 month) and neighborhood of residence were assessed for serum HBsAg, anti-HBc, anti-HBs, anti-HCV and testosterone. Among controls, serum testosterone levels were similar between those who had no markers of HBV infection, those who were positive for anti-HBs only and those who were positive for anti-HBc but negative for HBsAg. However, the geometric mean level of testosterone in HBsAg-positive controls was 21% higher relative to HBsAg-negative controls and the difference was statistically significant (2-sided p = 0.0006). Relative to controls, HCC cases had a significantly higher mean level of testosterone at the time of recruitment (570 vs. 485 ng/dl, 2-sided p = 0.0005), but the difference was explicable on the basis of a higher proportion of HBsAg-positive individuals among cases than controls (p = 0.42 after adjustment for HBsAg status).

Age Factors↗

PubMed1995

Alterations in the sensitivity of serum insulin-like growth factor 1 and insulin-like growth factor binding protein-3 to octreotide in polycystic ovary syndrome.

OBJECTIVE: To determine if the somatostatin analog, octreotide, affects insulin and related peptides and, hence, androgen levels differently between polycystic ovary syndrome (PCOS) patients and controls. DESIGN: Prospective controlled trial. SETTING: Reproductive endocrinology clinic of our medical center. PATIENTS: Eleven women with PCOS and six matched ovulatory controls. INTERVENTIONS: Octreotide (100 micrograms) was administered subcutaneously in the midfollicular phase. Serum was obtained before and at 60, 120, 180, and 240 minutes after octreotide. MAIN OUTCOME MEASURES: Fasting insulin, insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), T, androstenedione (A), and LH. RESULTS: In PCOS, baseline levels of T, A, LH, and fasting insulin were significantly higher than in controls. Pretreatment IGF-1 and IGFBP-3 levels were similar in PCOS and controls. Octreotide reduced fasting insulin levels significantly but to a similar degree in control and PCOS patients (77% and 90%, respectively). Both groups also experienced a significant decrease in LH levels after octreotide administration, but no significant changes were demonstrated in serum T or A. However, serum IGF-1 suppression in PCOS was greater (63% versus 8% in controls). Serum IGFBP-3 levels increased after octreotide administration in both groups with a larger increase (40%) occurring in the PCOS patients. CONCLUSIONS: These data suggest that women with PCOS may be more sensitive to the effects of octreotide in decreasing IGF-1 and increasing IGFBP-3. Although no significant changes could be demonstrated in ovarian androgens after a single dose, octreotide effectively reduced serum LH and insulin and, as such, may prove useful in treating some patients with PCOS.

Adolescent↗

PubMed1995

Metabolism of dihydrotestosterone to 5 alpha-androstane-3 alpha, 17 beta-diol glucuronide is greater in the peripheral compartment than in the splanchnic compartment.

OBJECTIVE: To compare the peripheral versus the splanchnic contribution to the formation of 3 alpha-diol G. DESIGN: Prospective study in various groups of women and men. SETTING: Reproductive Endocrine service of our University Medical Center. PATIENTS: Six normal ovulatory women, five hirsute women with polycystic ovary syndrome, and six normal men. INTERVENTIONS: All subjects received IV dihydrotestosterone (DHT) infusions as well as percutaneous administration of DHT. Serum was obtained at multiple time points before and after each administration of DHT. MAIN OUTCOME MEASURES: Comparison of serum levels of DHT, 3 alpha-androstanediol (3 alpha-diol), 3 alpha-diol G, and androsterone glucuronide in the three groups. RESULTS: Steady-state levels of DHT were similar in the three groups and were also similar after the two different routes of administration. However, ratios of 3 alpha-diol G to DHT were significantly greater after percutaneous gel than after IV administration in all three groups. This also was the case for the ratio of unconjugated serum 3 alpha-diol to DHT. Levels of androsterone glucuronide were similar with the different routes of administration. CONCLUSION: Using normal routes of administration and, in attempting to assess in vivo metabolism of DHT, our data confirm that the skin is the major site of unconjugated 3 alpha-diol and 3 alpha-diol G formation. Serum 3 alpha-diol G, therefore, appears largely to reflect skin DHT metabolism.

Administration, Cutaneous↗

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↗

PubMed1995

A prospective randomized trial comparing finasteride to spironolactone in the treatment of hirsute women.

Enhanced 5 alpha-reductase activity has been found in the skin of the majority of women with hirsutism. Finasteride is a specific competitive inhibitor of 5 alpha-reductase, preferentially inhibiting the type 2 isoenzyme. Therefore, we randomly assigned 14 hirsute women in a 2:1 ratio to 1 of 2 treatment arms: 1) finasteride (F) treatment (n = 9; 5 mg, orally, daily), or 2) spironolactone (S) treatment (n = 5; 100 mg, orally, daily). Each group was treated for 6 months. Patients were evaluated at baseline and after 3 and 6 months of treatment. The 2 groups were similar in age, weight, hip/waist ratio, baseline Ferriman-Gallwey score (F, 19 +/- 2; S, 19 +/- 2), and baseline androgen levels. Finasteride treatment resulted in a significant increase in testosterone (T; P < 0.01) and the T/dihydrotestosterone ratio (P < 0.01). Finasteride caused a significant decrease in 5 alpha-androstane-3 alpha,17 beta-diol glucuronide (3 alpha-diolG; P < 0.05), the 3 alpha-diolG/T ratio (P < 0.01), and the 3 alpha-diolG/androstenedione ratio (P < 0.05). All changes were consistent with 5 alpha-reductase inhibition. In contrast, spironolactone treatment did not result in significant changes in serum hormone levels. Both treatments produced a significant decrease in anagen hair diameters [F, -14.0 +/- 6.7% (P < 0.05); S, -13.4 +/- 3.8% (P < 0.05)] and Ferriman-Gallwey scores [F, -2.1 +/- 0.4 (P < 0.05); S, -2.5 +/- 0.7 (P < 0.05)]. In conclusion, despite significantly different effects on androgen levels, finasteride and spironolactone treatment resulted in a similar clinical effect on hirsutism. Both caused significant, but limited, improvement in hirsutism. Although promising, further studies with finasteride are needed to verify its effectiveness as a treatment for hirsutism. Such studies will also provide a better understanding of the relative contribution of 5 alpha-reductase isoenzymes to hirsutism.

Adolescent↗

PubMed1995

Time-dependent changes in serum 3 alpha-androstanediol glucuronide correlate with hirsutism scores after ovarian suppression.

The clinical utility of serum 3 alpha-androstanediol glucuronide level has been controversial. Among the concerns regarding its lack of utility has been the finding that suppression of serum 3 alpha-androstanediol glucuronide does not occur readily with treatment. We hypothesized that because the treatment of hirsutism requires a prolonged duration, a longer observation period is required for changes in serum 3 alpha-androstanediol glucuronide to be measured. Therefore, we studied the clinical and hormonal changes in 11 women treated for hirsutism with a gonadotropin-releasing hormone agonist (GnRH-a) for 1 year. A progressive reduction in Ferriman-Gallwey scores occurred, which was significant at 6 weeks and was maximal at 12 months. Serum 3 alpha-androstanediol glucuronide and another peripheral marker, androsterone glucuronide, also fell commensurately. While there was no correlation at 3 months, by 6 weeks a significant correlation had occurred between the suppression in Ferriman-Gallwey scores and the suppression of serum 3 alpha-androstanediol glucuronide and androsterone glucuronide. The suppression of these steroids also correlated with the suppression of non-sex hormone-binding globulin-bound testosterone. These data confirm that markers of peripheral androgen action, particularly serum 3 alpha-androstanediol glucuronide, reflect the clinical manifestation of hirsutism. However, it appears that modifications in peripheral androgen activity (presumably through 5 alpha-reductase activity) are time-dependent, and that serum markers reflect changes after 6 months of treatment.

Adult↗

PubMed1994

New knowledge in the physiology of hormonal contraceptives.

The present review addresses some of the new knowledge regarding the physiology and mechanisms of action of hormonal contraceptives. Specific topics that are discussed include oral contraceptives, intravaginal rings, long-term contraception, gonadotropin-releasing hormone agonists and antagonists, and antiprogestins. It has been shown that in combined oral contraceptives, lower doses of the new progestins (desogestrel, norgestimate, and gestodene) can be used to inhibit ovulation compared with norethindrone and levonorgestrel. In addition, lower doses of ethinyl estradiol are now used with progestins. Estrogen has been added to intravaginal rings containing levonorgestrel or norethindrone acetate to reduce frequency of bleeding. A new ring containing 3-keto-desogestrel is under evaluation. The use of subdermal implants containing levonorgestrel is currently a popular and highly effective method of long-term contraception. Studies show that gonadotropin-releasing hormone agonists and antagonists can provide ovarian suppression, and antiprogestins such as RU486 effectively block the midcycle gonadotropin surge. These and other novel methods of hormonal contraception are still years away from general use.

Administration, Intravaginal↗