Angiotensin converting enzyme in bovine ovarian follicular fluid and its relationship with oestradiol and progesterone.

CONTENT: The purpose of the present study was to identify angiotensin converting enzyme (ACE) in bovine ovarian follicular fluid and to relate the ACE activity to the phase of the oestrous cycle, pregnancy, and the follicular fluid concentrations of oestradiol and progesterone. The ACE activity was similar to that found in bovine serum and was completely inhibited by the specific ACE inhibitor captopril. The 50% inhibitory concentration (IC50) was 1.4 x 10(-8) mol/l (range 0.8 x 10(-8) to 5.0 x 10(-8) mol/l; n=6), which is similar to that found in bovine and human serum. The ACE activity did not differ in the pre-ovulatory and luteal phase, pregnancy or cystic follicles. It correlated with the follicular fluid concentration of progesterone in cycling cows (rho=0.476; p < 0.005; n=36), but did not correlate with the diameter of the follicles, the follicular fluid concentration of oestradiol or the ratio between the oestradiol and progesterone concentrations. The demonstration of ACE in bovine ovarian follicular fluid provides further evidence for the presence of a local renin-angiotensin system in the bovine ovary.

Morning versus evening administration of estradiol to girls with turner syndrome receiving growth hormone: impact on growth hormone and metabolism. A randomized placebo-controlled crossover study.

UNLABELLED: Timing of 17beta-estradiol (E2) administration in relation to that of GH could influence the "first pass effect" of E2 on hepatic IGF-I secretion. In order to test this hypothesis, a randomized double-blind placebo-controlled crossover study was conducted. Nine Turner girls (12.8-20.0y) were treated for 2 mo periods with GH 0.1 IU/kg/d sc at bedtime, and oral E2 6-11 microg/kg/d in the morning and placebo in the evening in one 2-mo period and vice versa in the other period. After each period, 24-h blood sampling was performed. IGF-I and mean 24-h integrated GH were comparable. However, the IGF-I/IGFBP-3 ratio was higher (p = 0.05) and insulin levels were lower after evening administration of E2 (24 h: p = 0.03). During an oral glucose tolerance test in the morning, glucagon and insulin were lower following evening E2 administration (ANOVA: glucagon, p = 0.03; insulin, p = 0.04), as well as insulin resistance tended to be lower (p = 0.09). CONCLUSION: The timing of oral E2 supplementation modulates the IGF-I/IGFBP-3 ratio, insulin and glucagon levels in Turner syndrome during GH treatment, Evening administration of oral estrogen together with evening injections of GH may be preferable.

Reduced androgen levels in adult turner syndrome: influence of female sex steroids and growth hormone status.

BACKGROUND AND OBJECTIVES: In girls with Turner syndrome androgen levels are reduced. In order to assess androgen status in women with Turner syndrome, we compared untreated adult women with Turner syndrome with a group of normal women. In addition, the effects of female sex hormone replacement therapy and GH status on the levels of circulating androgens in Turner syndrome was examined. DESIGN: All patients were receiving female hormone replacement therapy (HRT), which was discontinued four months prior to the initial examination. Patients were studied before and during HRT. Following the initial evaluation, patients were given cyclical HRT for six months consisting of either oral substitution (17beta-oestradiol with norethisterone from day 13-22), or transdermal oestrogen substitution (17beta-oestradiol) with 1 mg norethisterone administered orally from day 13-22. Control subjects were studied once in the early follicular stage of the menstrual cycle. SUBJECTS: The study group consisted of 27 (33.2 +/- 7.9 years) patients with Turner syndrome and an age matched control group of 24 (32.7 +/- 7.6 years) normal women. MEASUREMENTS: Body composition measures, SHBG, testosterone (T), free testosterone (FT), dihydrotestosterone (DHT), alpha-4-androstendione (A), dehydroepiandrosterone sulphate (DHEAS), 17beta-oestradiol (E2), oestrone (E1), oestrone sulphate (ES), 24 h integrated GH concentration (ICGH), insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein (IGFBP-3) were determined at baseline and after six months in women with Turner syndrome, and at baseline in control women. RESULTS: Circulating levels of A, T, FT, DHT, and SHBG were reduced by 25-40% in comparison with age matched normal women. The level of DHEAS was normal. The level of E2 was undetectable and levels of E1 and ES were very low in untreated Turner women. Treatment with 17beta-oestradiol and norethisterone increased oestrogen to levels comparable to those of normal women, while further decreasing FT (P = 0.02), DHT (P = 0.04), and T (P = 0.1). In untreated women with Turner syndrome IGF-I correlated significantly with DHEAS (R = 0.503, P < 0.01), while in normal women IGF-I correlated with A (R = 0.637, P < 0.01), T (R = 0.536, P < 0.01), and FT (R = 0.700, P < 0.01). During hormonal replacement in women with Turner syndrome IGF-I correlated significantly with DHEAS (R = 0.547, P < 0.01). Employing multiple regression analysis IGFBP-3, ICGH, DHEAS and fat free mass explained 85% (adjusted R = 0.92, P < 0.0005) of the variation in the level of IGF-I in untreated Turner syndrome. In treated Turners IGFBP-3, ICGH, SHBG, T, and FT explained 78% (adjusted R = 0.88, P < 0.0005). In controls IGFBP-3, SHBG, BMI and age explained 74% (adjusted R = 0.86, P < 0.0005) of the variation in IGF-I, while GH status did not contribute at all. CONCLUSION: The present study shows that many adults with Turner syndrome have reduced levels of circulating androgens, compared with an age-matched group of normal women. Conditions associated with Turner syndrome such as increased prevalence of sexual problems, reduced bone mineral content, osteoporosis, and an increased incidence of fractures and alterations in body composition could perhaps be alleviated or abolished by substitution with a low dose of androgens. Treatment with female hormonal replacement therapy is associated with a decrease in testosterone, free testosterone and dihydrotestosterone, possibly mediated by the androgenic effect of norethisterone. Furthermore significant differences in sex steroid levels, GH status and indices of body composition can be compatible with comparable levels of IGF-I in two very different groups of individuals.

Relationship between follicular fluid steroids and tissue renin concentrations and secretion rates in bovine ovaries.

The relationship between follicular fluid concentrations of oestradiol (E2) and progesterone (P4), and follicular wall tissue renin concentrations and in-vitro secretion rates was investigated. The follicular fluid concentrations of prorenin correlated negatively with oestradiol and the E2/P4 ratio, and positively with progesterone in accordance with earlier findings. The high concentrations of active renin and prorenin in the follicular wall tissue, and the secretion rates of both active renin and prorenin all correlated positively with oestradiol and the E2/P4 ratio, but negatively with progesterone. These findings suggest that atretic follicles have higher follicular fluid renin concentrations but lower tissue renin concentrations and in-vitro secretion rates than healthy non-atretic follicles. The high follicular fluid prorenin concentrations in atretic follicles are most likely caused by a high prorenin secretion rate earlier in the oestrus cycle. The existence of relationships between the follicular fluid steroids and the follicular wall concentrations and secretion rates of active renin and prorenin indicates an interaction between the reninangiotensin system and steroidogenesis, but it may also reflect regulation by common factors, such as gonadotropins.

Steroid metabolism in the hormone dependent MCF-7 human breast carcinoma cell line and its two hormone resistant subpopulations MCF-7/LCC1 and MCF-7/LCC2.

Androgen and estrogen metabolism was investigated in the hormone-dependent human breast cancer cell line MCF-7 and its two hormone-resistant sublines MCF-7/LCC1 and MCF-7/LCC2. Using the product isolation method, the activity of aromatase, 5alpha-reductase, 3alpha/beta-hydroxysteroid oxidoreductase and 17beta-hydroxysteroid oxidoreductase were investigated isolating the following steroids: estriol (E3), estradiol (E2), estrone (E1), 3alpha/beta-androstanediol (A-diol), testosterone (T), dihydrotestosterone (DHT), androsterone (AND), androstenedion (4-AD) and androstanedione (A-dion). For all experiments, cells were preincubated with cortisol and subsequently incubated with [14C]T or [14C]4-AD as the substrate in medium without phenol red and with serum charcoal stripped of steroids. The results showed no aromatase activity in any of the cell lines under the experimental conditions used, and preincubation with cortisol had no effect on the enzyme activity. With [14C]T as the substrate, the metabolized level of DHT was very similar in the three cell lines, though MCF-7/LCC1 and MCF-7/LCC2 utilized the substrate to a much lesser extent. The amount of DHT and 4-AD produced were comparable in the two hormone-resistant cell lines, while the amount of 4-AD was significantly higher in MCF-7 cells. No differences in enzyme activity were found in the three cell lines when [14C]4-AD was used as the substrate. This study showed an altered androgen metabolism in the MCF-7/LCC1 and MCF-7/LCC2 sublines compared to the parent MCF-7. However, since treatment with DHT and T inhibited cell growth equally well in all three tumor cell lines, it is unlikely that the found differences in steroid metabolism was involved in the acquisition of the endocrine resistance of the two MCF-7 sublines.

Simple mucin-type carbohydrates in normal and malignant human endometrium.

The simple mucin-type carbohydrate antigens, Tn, sialosyl-Tn, and T, are tumor-associated antigens of adenocarcinomas. We evaluated by immunohistochemistry the expression of Tn, sialosyl-Tn (s-Tn), T, and sialosyl-T (s-T) antigens in normal nonsecretory, early gestational, and malignant human endometrium in relation to genetic (ABO/Lewis blood-type) and hormonal factors. The blood group status had no influence on staining. Tn and s-Tn antigens were infrequently demonstrated in normal nonsecretory endometria but showed an increased expression in adenomatous hyperplasias and endometrial carcinomas, which was unrelated to estradiol (E2) levels, grade, and stage. The T disaccharide was demonstrated infrequently in both normal and malignant endometrium. Staining for T antigen showed an inverse correlation to serum E2 levels. In contrast, s-T antigen showed a pronounced but varied expression in normal and malignant endometrium, and the expression of s-T antigen was positively correlated with E2 levels in serum. Our findings suggest a hormonal influence on expression of simple mucin-type carbohydrates in human endometrium. However, the accumulation of Tn and s-Tn antigens in malignant endometrial cells seem to be unrelated to both genetic and hormonal factors. Because s-Tn is also expressed by secretory endometria, only Tn antigen can be considered a "tumor-associated" antigen of endometrial tissue.

Regulation of angiotensin II receptor expression in ovarian follicles. A review.

The regulation of angiotensin (Ang) II receptor expression in ovarian follicles was reviewed. Ang II receptor expression, assessed as the Ang II binding capacity, varied with the animal species and the developmental stage of the follicle. In cows, the expression correlated positively with follicular size and negatively with the active renin concentration in the follicular wall tissue. No relations were found to the follicular fluid concentrations of prorenin, estradiol or progesterone. In cell cultures, luteinizing hormone up-regulated Ang II receptor expression in cows, whereas it was decreased by follicle-stimulating hormone, Ang II and testosterone in rats. These data support the concept of an active and regulated RAS in ovarian follicles. The species differences in Ang II expression suggest varying functional roles of the RAS between species.

Estrogen- and progesterone receptors in normal cycling endometrium as studied by end-point titration.

A thorough knowledge of the normal physiological fluctuations in estrogen- (ER) and progesterone receptors (PgR) is essential to characterize the changes in ER and PgR in the abnormal endometrium. We investigated the distribution of ER and PgR in frozen human cycling endometrial tissue using the commercially available ER- and PgR-ICA kits. Two-fold end-point titration (EPT) of ER and PgR antibodies was implemented to semi-quantitate more accurately ER and PgR. Semiquantitation of ER and PgR using EPT was significantly correlated to results obtained using either simple scoring or enzyme-immunoassay (EIA) methods. ER and PgR staining fluctuated in relation to the menstrual cycle. In most subphases PgR exceeded ER in both epithelial and stromal cells. Highest levels of ER and PgR were demonstrated in the glands of the functionalis in mid-to-late proliferative phases, whereas both receptors were almost undetectable by immunohistology in the glands of mid-to-late secretory phases. Endometrial stromal cells had high and nearly constant EPT values for PgR, but low values for ER throughout the menstrual cycle. EPT values for ER and PgR were generally higher in the basalis than in the functionalis but showed similar cyclic fluctuations. Our results further substantiate the view that the response to hormonal stimulation is cell-type specific, and suggest differences in steroid metabolism according to cell type and layer.

Angiotensin II receptor density in bovine ovarian follicles relates to tissue renin and follicular size.

1. The purpose of this study was to investigate angiotensin II (AII) receptors in isolated bovine ovarian follicles and the relationship of their density to follicular concentrations of prorenin, active renin, oestradiol and progesterone. 2. Displacement of [125I]-[Sar1-Ile5-Ile8]-AII binding by the AII receptor antagonists PD 123319 and Losartan (DuP 753) confirmed that follicular AII receptors are of subtype 2 (AT2 receptor). 3. The dissociation constant (Kd) for [Ile5]-AII (human AII) was 0.84 (range 0.51-1.47) nmol/L. The receptor density varied between 90 and 5990 (mean 1640) fmol/mg membrane protein. 4. The follicular AII receptor density correlated positively with follicular diameter (Spearman's rho = 0.518; P < 0.003) and tissue weight (Spearman's rho = 0.636; P < 0.0001), and negatively with the active renin concentration in the follicular wall (Spearman's rho = -0.399; P < 0.02). The AII receptor density did not correlate with the follicular fluid concentrations of prorenin, active renin, oestradiol (E2), progesterone (P4) or the E2/P4 ratio. The follicular fluid concentrations of prorenin correlated negatively with the E2/P4 ratio (Spearman's rho = -0.716; P < 0.0001). 5. The inverse relationship between AII receptor density and the high active renin concentrations in the follicular wall suggests an active regulated tissue renin-angiotensin system. A high AII receptor density is a general feature of large bovine ovarian follicles.

Sex hormone levels in postmenopausal women with advanced metastatic breast cancer treated with CGS 169 49A.

30 postmenopausal patients with metastatic breast cancer were treated with three different doses of fadrozole hydrochloride (CGS 169 49A), a non-steroidal competitive aromatase inhibitor. The effect of 0.5, 1 and 2 mg given twice daily upon the levels of oestrogens, their androgen precursors and upon the concentration of sex hormone binding globulin (SHBG) was investigated after 1 and 3 months and then every 3 months until progression of disease. A significant reduction in the serum concentration of oestrone (P < 0.0001) was obtained at all doses. Also, the serum concentration of oestrone sulphate was significantly reduced (P < 0.0001). However, after 1 month, the concentration was significantly different from pretreatment levels (P < 0.01) only at the 4 mg daily dose. A decline was also observed in the concentration of SHBG (P < 0.05), with a concomitant elevation of the percentage non-SHBG-bound oestradiol. The androgens, testosterone and dehydroepiandrosterone sulphate, were unaltered during treatment, while androstendione was significantly elevated at the 2 mg daily dose (P < 0.001).

Type-1 chain histo-blood group antigens (Le(a), monosialosyl-Le(a), disialosyl-Le(a), Le(b), and H) in normal and malignant human endometrium.

Type-1 chain histo-blood group antigens such as the Lewis (Le)a, monosialosyl-Le(a), Le(b) and H antigens show an increased expression in endometrial carcinomas. However, the possibility that these antigens are expressed under genetic or hormonal influence in endometrial carcinomas has not been considered. In the present study, the expression of type-1 chain carbohydrate antigens in normal and malignant endometrium was evaluated by immunohistochemistry and related to both genetic and hormonal factors. The glands of normal, non-secretory endometria expressed, in contrast with surface epithelial cells, Le(a), Le(b), disialosyl-Le(a), and H determinants infrequently. Adenomatous hyperplasias and endometrial carcinomas showed an increased expression of type-1 chain carbohydrates that was qualitatively influenced by the erythrocyte Lewis phenotype and the secretor status. Whereas Le(a+b-) non-secretors mainly accumulated Le(a) antigen, and only limited amounts of Le(b) antigen, Le(a-b+) secretors expressed H, Le(b) and Le(a) antigens. The expression of type-1 chain antigens showed no association with the serum-oestrogen level or to the hormone-receptor status. Thus the Lewis secretor status has a qualitative influence on the increased expression of type-1 chain antigens, which, however, seem to be unrelated to hormonal factors. Our findings suggest an increased activity of the Se-gene-defined or a closely related fucosyl-transferase in neoplastic endometrial epithelial cells.

Expression of type-2 histo-blood group carbohydrate antigens (Le(x), Le(y), and H) in normal and malignant human endometrium.

Changes in expression of histo-blood group ABH and Lewis antigens are common alterations in carcinomas. Using immunohistochemistry, we have evaluated the expression of type-2 histo-blood group antigens in normal and malignant endometrial tissues in relation to genetic and hormonal factors. The Le(x), sialosyl-Le(x), and Le(y) antigens were inconstantly expressed in the normal endometrium. The expression was uninfluenced by the secretor status but was related to the ABO blood group status in Oestradiol (E2) stimulated endometria. Le(y) was expressed most frequently in proliferating endometria from blood group 0 individuals. Le(x) and Le(y) were maximally expressed in atrophic endometria, and Le(x) and Le(y) staining scores correlated inversely with serum levels of E2 in normal, non-secretory endometria. No correlation was found in adenomatous hyperplasias and endometrial carcinomas, which when compared with atrophic endometria, showed a loss of Le(x) and Le(y) and an increased H-carbohydrate expression at apical membranes. Carcinomas from non-secretors showed lower expression of Le(y) and H-antigens than carcinomas from secretors. Our findings suggest that the genetic and hormonal influence on glycosylation based on type-2 chain carbohydrates differ between normal and malignant endometrium. This difference is probably related to specific tumour-associated qualitative and quantitative changes in the fucosyltransferases.

A two-year double-blind controlled study of the clinical effect of combined and sequential postmenopausal replacement therapy and steroid metabolism during treatment.

A total of 151 postmenopausal women were randomly allocated to 3 groups for treatment with hormone replacement therapy. One group received combined therapy (2 mg oestradiol (E2) and 1 mg norethisterone acetate (NETA) daily), the second group was placed on sequential therapy (2 mg E2 for 12 days, 2 mgE2 and 1 mg NETA for 10 days and 1 mg E2 for 6 days), while the third was given placebo. Treatment was administered over 24 cycles of 28 days. The two active treatments were equally effective in relieving climacteric symptoms. In the combined therapy group, 62% of the women experienced spotting and/or breakthrough bleeding during the first 3 cycles; thereafter this proportion decreased to between 3 and 18% in each of the following three-cycle periods. Sixty-four percent (64%) of these women had no more bleeding after the first 3 cycles. Endometrial atrophy was detected in 93% of the women in this group after 24 cycles of therapy. Bleeding irregularities occurred during the first 3 cycles in 27% of the patients treated with sequential therapy and in 21% of those receiving placebo. In the subsequent 3-cycle periods these figures fell to below 10% in the 2 groups. In all 3 groups weight remained stable but blood pressure increased equally in the actively treated groups and the placebo group. The levels of follicle-stimulating hormone (FSH), sex-hormone-binding globulin (SHBG) and the free fraction of E2 in serum were significantly lower in the combined therapy group than in the sequential therapy group. The higher level of free E2 in the latter group may have been caused by a decrease in metabolism associated with the increased SHBG concentration. It was concluded that combined treatment with E2 and NETA might provide an alternative to sequential treatment in postmenopausal women willing to tolerate the initial high risk of breakthrough bleeding/spotting in order to avoid subsequent regular bleeding. In the subgroup of women in whom bleeding irregularities continue, sequential treatment should be considered.

Cortical bone mass, composition, and mechanical properties in female rats in relation to age, long-term ovariectomy, and estrogen substitution.

The study comprised 12 groups of female rats: 6 groups of intact rats killed at 2, 6, 9, 12, 15, and 24 months of age, 4 groups of rats ovariectomized at 6 months and killed together with the intact rats at 9, 12, 15, and 24 months of age, and 2 groups of rats (one intact and one ovariectomized) treated with estrogen (2 micrograms estradiol valerate/rat/week s.c.) for 8 months before they were killed at 24 months of age. The composition, dimensions, and mechanical strength of intact bone and bone collagen from femoral diaphyses were investigated in relation to age, ovariectomy, and estrogen administration. Up to 6-9 months of age, the axial length, percentage ash, density, and compressive mechanical stress increased, whereas percentage collagen decreased. An age-related increase in bone mass, cross-sectional area, and wall thickness and a decrease in mechanical quality of bone collagen were apparent from 2 to 24 months of age. An age-related periosteal bone formation and the absence of endosteal bone resorption were demonstrated in intact rats. Compared with intact rats, ovariectomy was followed by an increase in body weight, a tendency to reduced percentage ash and a depressed bone mass, cross-sectional area, and wall thickness of femoral diaphyses. The compressive mechanical stress of intact bone and the mechanical quality of bone collagen were unaffected by ovariectomy. Ovariectomy did not influence the periosteal bone formation but induced an endosteal bone resorption not present in the intact rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Possible interaction between oxcarbazepine and an oral contraceptive.

The effect of oxcarbazepine (OCBZ) on the kinetics of an oral contraceptive containing ethinyloestradiol (EE) and levonorgestrel (LNG) was investigated in 13 healthy female volunteers who had previously received the contraceptive for at least 3 months. After 15 days of the first study cycle, each subject received, in addition to the oral contraceptive, 300 mg OCBZ on day 16, 300 mg twice daily on day 17, and 300 mg three times daily from day 18 of the first cycle to day 18 of the next menstrual cycle. The area under the curve values for both EE and LNG decreased when OCBZ was given with the oral contraceptive (p = 0.006, analysis of variance). The results indicate that OCBZ, like most antiepileptic drugs (AEDs), decreases the bioavailability of EE and LNG, perhaps by affecting metabolism or protein binding.

Serum sex hormones and endurance performance after a lacto-ovo vegetarian and a mixed diet.

Serum sex hormones and endurance performance after a lacto-ovo vegetarian and a mixed diet. Med. Sci. Sports Exerc., Vol. 24, No. 11, pp. 1290-1297, 1992. The effect of a lacto-ovo vegetarian (V) and a mixed, meat-rich (M) diet on the level of serum sex hormones, gonadotropins, and endurance performance of eight male endurance athletes was investigated in a 2 x 6 wk cross-over study. The energy contribution from carbohydrate, fat, and protein was 58%, 27%, and 15% on the V diet and 58%, 28%, and 14 E% on the M diet. For total fasting serum testosterone (T) there was a significant interaction between diet and time (P < 0.01). Thus, the V diet resulted in a lower total T level (13.7, 9.8-32.4 nmol.l-1) (median and range) compared with the M diet (17.4, 11.8-33.5 nmol.l-1). During exercise after 6 wk on the diets total T was also significantly lower on the V than on the M diet (P < 0.05). Serum free testosterone, however, did not differ significantly during the 6 wk dietary intervention periods and neither did serum concentrations of sex hormone binding globulin, dihydrotestosterone, dehydroepiandrosterone sulphate, 4-androstenedione, estrone, estradiol, estrone sulphate, or gonadotropins. Endurance performance time was higher for six and lower for two after the mixed diet compared with the vegetarian diet. This was not significant, however. In conclusion, 6 wk on a lacto-ovo vegetarian diet caused a minor decrease in total testosterone and no significant changes in physical performance in male endurance athletes compared with 6 wk on a mixed, meatrich diet.

The contribution of body composition, substrates, and hormones to the variability in energy expenditure and substrate utilization in premenopausal women.

Twenty-four-hour energy expenditure and substrate use were measured by indirect calorimetry in respiration chambers on a fixed physical program and related to body composition and plasma concentrations of various substrates and thermogenic hormones. Fifty premenopausal women with a wide range of body weight were examined in the follicular menstrual phase under weight stable conditions. Most of the variance in the sleeping energy expenditure (82%) was accounted for by two covariates, lean body mass (75%, P less than 0.0001), and fat mass (7%, P less than 0.0001). An additional 6% of the variance in sleeping energy expenditure was accounted for by plasma androstenedione concentration (4%, P = 0.0005) and by free T3 index (2%, P = 0.03). Thus physiological variation among individuals in plasma androstenedione concentration may result in a difference in energy expenditure of 908 kJ/day and the corresponding variation in free T3 index may result in a difference between individuals of 594 kJ/day. Fifty four percent of the variation in carbohydrate oxidation rates was accounted for by 24-h energy balance, and by plasma concentrations of insulin, nonesterified fatty acids, and estradiol. Waist circumference, plasma nonesterified fatty acids, and estradiol concentrations explained 49% of the variance in 24-h lipid oxidation. An obese subgroup of women (n = 27) had significantly higher 24-h energy expenditure, lipid, and carbohydrate oxidation rates than an age-matched normal weight group (n = 16), but the entire group difference in energy expenditure was explained by differences in body composition. We conclude that physiological variations in plasma androstenedione and T3 concentrations contribute to the interindividual variance in energy expenditure of women, and their role is not different in obese women. A positive energy balance and increased insulin action may be mediators of the higher carbohydrate oxidation in obesity, whereas an increased substrate availability seems to bring about the increased lipid oxidation.

Menopausal age and sex hormones in postmenopausal women with alcoholic and non-alcoholic liver disease.

In order to evaluate age at menopause and serum sex hormone profiles in postmenopausal women with stable chronic liver disease, six non-cirrhotic alcoholics, 13 with alcoholic cirrhosis, eight with non-alcoholic cirrhosis, and 46 healthy controls were studied. In all three groups, patients were significantly (p less than 0.05) younger at the time of natural menopause than controls. Compared to controls, non-cirrhotic alcoholic women had significantly (p less than 0.05) reduced levels of DHAS, significantly (p less than 0.05) more alcoholic cirrhotic women had detectable oestradiol concentrations, elevated concentrations of oestrone and sex hormone binding globulin (SHBG) and reduced levels of 5 alpha-dihydrotestosterone (DHT), while women with non-alcoholic cirrhosis had significantly elevated concentrations of SHBG and reduced levels of oestrone sulphate, DHT, androstenedione and dehydroepiandrosterone sulphate (DHAS) (p less than 0.05). The observed changes may be a consequence of liver disease since similar changes were observed in patients with alcoholic and non-alcoholic liver disease, but an additional effect of alcohol cannot be excluded.

Sex hormones in postmenopausal women with primary biliary cirrhosis.

To evaluate serum sex hormone profiles in nonalcoholic postmenopausal women with liver disease, 25 women with primary biliary cirrhosis (11 in cirrhotic stage) and 46 healthy controls were studied. The patients had significantly (p less than 0.05) elevated serum concentrations of estrone and androstenedione and significantly (p less than 0.05) lower concentrations of estrone sulfate, dehydroepiandrosterone sulfate and 5 alpha-dihydrotestosterone compared with the 46 controls. Serum concentrations of sex hormone binding globulin, testosterone, non-sex hormone binding globulin-bound testosterone and non-protein-bound testosterone did not differ significantly (p greater than 0.05) between primary biliary cirrhosis patients and controls. Patients in the cirrhotic stage had significantly (p less than 0.05) higher concentrations of sex hormone binding globulin than did controls. Patients in the cirrhotic stage had significantly (p less than 0.05) higher sex hormone binding globulin and estrone sulfate levels compared with noncirrhotic patients with primary biliary cirrhosis. Otherwise, no significant differences were observed between cirrhotic and noncirrhotic patients. The observed changes in steroid concentrations may be a consequence of hepatic dysfunction.

Testis cancer. Ichthyosis constitutes a significant risk factor.

Testis cancer and ichthyosis are both relatively rare diseases. Hence the finding of six individuals with both these conditions in a small population with testicular cancer is highly conspicuous and indicates some kind of connection among such persons. Despite the identical clinical appearances of their ichthyoses, three of the ichthyotic subjects had no measurable activity of the enzyme, steroid sulfatase (STS) in leucocytes, a distinct characteristic of recessive X-linked ichthyosis (RXLI). However, the remaining three subjects had normal STS activity, a strong indicator of autosomal dominant ichthyosis (ADI). The STS activity in patients with testicular cancer who do not have ichthyosis (N = 30) was also within the normal range. The patients with testicular cancer with no skin disease had elevated serum levels of 4-androstenedione (4-AD), follicle stimulating hormone (FSH), and luteinizing hormone (LH) but had reduced levels of estrone and estrone sulfate. The other serum parameters measured did not significantly differ from normal levels. In essence, the hormone levels obtained for the patients with ichthyotic testicular cancer followed the same pattern, although their dehydroepiandrosterone sulfate (DHEAS) and estrone sulfate levels tended to be slightly higher than normal. However, no conspicuous aberrations in any of the parameters examined were observed, and why men with ichthyosis are at high risk for testicular cancer remains an unresolved issue.