Effects of pulsed electromagnetic fields on the mRNA expression of CAII and RANK in ovariectomized rats.

The present study was designed to determine the effects of pulsed electromagnetic fields (PEMFs) on the mRNA expression of the carbonic anhydrase II (CAII) and receptor activator of NF-κB (RANK) in ovariectomized rats. A total of 48 SD rats were randomly divided into four groups [Sham, OVX, PEMFs, and E(2) (premarin)], 12 rats in each group. Rats in the Sham group received sham ovariectomy, while rats in OVX, PEMFs, and E(2) groups received ovariectomy. Twelve weeks following the surgery, rats (whole body) in the PEMFs group were exposed to PEMFs for 30 days with 3.8 mT, 8 Hz, and 40 min per day; rats in the E(2) group were administered premarin (0.0625 mg/kg/d; intragastric administration 1-2 ml/100 g). Rats in the Sham and OVX groups housed in the same conditions. At the end of intervention, the level of serum estradiol of rats was measured. The gene expression of CAII and RANK in the left ilium of rats was determined with real-time fluorescent-nested quantitative polymerase chain reaction. Compared with the Sham group, the level of serum estradiol in the ovariectomized group was significantly decreased (P < 0.05); compared with the OVX group, CAIImRNA expression was significantly decreased in the PEMFs group and E group (P < 0.05, 0.01, respectively). Compared with the E group, RANKmRNA expression was significantly higher in the PEMFs group (P < 0.05); although RANKmRNA expression decreased in PEMFs group, no statistically significant difference was found between PEMF group and OVX group (P = 0.82). These data suggest that PEMFs could regulate the expression of CAIImRNA in ovariectomized rats.

Plasma estrogen concentrations after oral and vaginal estrogen administration in women with atrophic vaginitis.

In this open-label, randomized, multiple-dose, two-treatment crossover study, 24 postmenopausal women with moderate to severe atrophic vaginitis received 0.3 mg conjugated estrogens daily for 14 days: 7 days orally (0.3 mg tablet) and 7 days vaginally (0.5 g cream). Steady-state plasma concentrations of E2 and estrone were one-third lower after vaginal versus oral administration of conjugated estrogens.

Effect of one-week treatment with vaginal estrogen preparations on serum estrogen levels in postmenopausal women.

OBJECTIVE: Approximately 50% of postmenopausal women suffer from vaginal atrophy, and a large proportion of them choose intravaginal estrogen preparations administered for local action to avoid systemic exposure to estrogens and its associated risk of breast and uterine cancer. The primary objective of this study was the evaluation of the systematic bioavailability of estradiol and estrone and the pharmacokinetics of two of the most frequently used intravaginal estrogen preparations, namely Vagifem and Premarin cream. DESIGN: While immunobased assays could not previously provide accurate measurement of serum estrogen concentrations in postmenopausal women, we have used validated mass spectrometry assays to measure the pharmacokinetics of serum estradiol and estrone during the 24 hours following the seventh daily application of 25 microg estradiol (Vagifem) and 1 g (0.625 mg) conjugated estrogens (Premarin) cream in 10 postmenopausal women in each group. RESULTS: Serum estradiol was increased on average by 5.4-fold from 3 to 17 pg/mL during the 24-hour period after daily administration of 25 microg estradiol or 1 g (0.625 mg) conjugated estrogens cream. Serum estrone, conversely, increased 150% with Vagifem and 500% with Premarin cream. CONCLUSIONS: The present data using validated, accurate, and sensitive mass spectrometry assays of estrogens show that the Vagifem pill and Premarin cream, after 1 week of daily treatment, cause an approximately fivefold increase in serum estradiol in postmenopausal women, thus indicating that the effects are unlikely to be limited to the vagina and that systemic actions are expected after application of these intravaginal estrogen preparations.

Steady-state pharmacokinetics of conjugated equine estrogens in healthy, postmenopausal women.

OBJECTIVE: To determine the steady-state exposure of conjugated and unconjugated estrogen components following oral administration of conjugated equine estrogens (2 0.625-mg tablets). STUDY DESIGN: A prospective, open-label, single-treatment study conducted at 1 clinical site with 12 healthy, postmenopausal women. Each subject received 7 daily doses of 2 conjugated equine estrogen (0.625-mg) tablets, and blood samples were taken on the last day of dosing for pharmacokinetic analysis of estrogen components. RESULTS: The major estrogen components after estrogen dosing (as determined by steady-state plasma concentration-time curves) were estrone (100 ng x h/mL), equilin (43.1 ng x h/mL) and delta8,9-dehydroestrone (13.6 ng x h/mL). Several 17beta-reduced forms of estrogen also had consistent plasma concentrations during a steady-state dosing interval. Mean t(max) values ranged from 6.2 to 9.0 hours after dosing, and the 24-hour profiles of the various plasma estrogen concentrations at steady state showed limited fluctuations. CONCLUSION: Oral dosing of conjugated equine estrogen at steady state resulted in consistent concentrations of estrogen components during a dosing interval.

Two estrogen replacement therapies differentially regulate expression of estrogen receptors alpha and beta in the hippocampus and cortex of ovariectomized rat.

As estrogens have been implicated in altered cognitive function associated with menopause, the purpose of the present study was to determine the regulatory effects of different estrogen preparations on the expression of estrogen receptor subtypes in the hippocampus and cortex of ovariectomized rats. The expression of estrogen receptor mRNA and protein was determined with RT-PCR and immunohistochemistry, respectively. Two estrogen reagents, Premarin and Progynova, were used in the present study. Premarin, a conjugated equine estrogen, down-regulated ER alpha expression in the hippocampus and cortex of ovariectomized rats and had no effect on levels of ER beta expression in the same two regions. However, Progynova (valerate estradiol) was shown to up-regulate ER beta expression in the hippocampus and cortex and had no effect on the levels of ER alpha expression. Our present data suggest that different estrogen reagents used in estrogen replacement therapy could have different regulatory effects on the expression of estrogen receptor subtypes, which might, at least in part, explain why clinically, different estrogen preparations have distinct estrogenic effects on target organs.

Supplementation with DHEA: effect on muscle size, strength, quality of life, and lipids.

OBJECTIVE: To evaluate the effects of combination estrogen/androgen therapy on muscle mass, strength and endurance, serum hormone and lipid profiles, and quality of life measures in postmenopausal women. METHODS: Prospective, randomized, placebo-controlled pilot study at a tertiary care medical center. Fifty postmenopausal women were randomized to a 12-week course of (1) dehydroepiandrostenedione (DHEA) 50 mg daily, (2) conjugated equine estrogen (CEE) 0.625 mg daily, (3) DHEA 50 mg+CEE 0.625 mg daily, or (4) placebo. Main outcome measures of lower extremity muscle (calf) mass, functional muscle parameters, serum hormone and lipid levels, and quality of life (QOL) were obtained at baseline and after treatment. Statistical analysis compared percent change from baseline values and treatment differences among outcomes. RESULTS: Significant increases in mean DHEA, DHEA sulfate (DHEA-S), testosterone, and androstenedione levels were noted with DHEA alone or combined DHEA/CEE treatments when compared with placebo. Compared with no hormone therapy, none of the supplemental hormone groups caused significant changes in muscle mass, muscle strength, muscle endurance, feelings of well-being, sleep, or sexual function. CONCLUSIONS: Androgen replacement therapy, with DHEA, to menopausal women increases serum androgen levels without any appreciable effect on muscle cross-sectional area, muscle strength, muscle function, or improvement in health-related QOL.

Differential role of K(ATP) channels activated by conjugated estrogens in the regulation of myocardial and coronary protective effects.

BACKGROUND: We have demonstrated that estrogen can reduce myocardial injury in ischemia-reperfusion via activation of ATP-sensitive potassium (K(ATP)) channels. We sought to determine whether the protective effect of estrogen extends to epicardial coronary artery with attenuated vasoconstriction in patients after angioplasty by activation of such channels. METHODS AND RESULTS: The study was designed to prospectively investigate 41 consecutive patients scheduled for elective coronary angioplasty. Pretreatment with estrogen limited myocardial ischemia during coronary occlusion and attenuated postangioplasty coronary vasoconstriction at the dilated and distal segments. An inhibitor of K(ATP) channels, glibenclamide, did not affect coronary vasomotor response, although it abolished the beneficial effect of estrogen on myocardial ischemia. Patients to whom estrogen was administered after the second balloon deflation experienced a similar magnitude of myocardial ischemia as controls but showed significantly attenuated vasoconstriction compared with controls (P=0.0001). Endothelin-1 levels from the great cardiac vein rose significantly from 1.9+/-0.4 to 3.1+/-0.6 pg/mL (P=0.001) 15 minutes after angioplasty in the control group; this was attenuated after estrogen was administered. Significant correlation was found between the changes in coronary vasomotion of the dilated segment and endothelin-1 levels (r=0.65, P<0.0001). CONCLUSIONS: These results demonstrate that estrogen is protective against both myocardial ischemia and coronary vasoconstriction through different mechanisms. The myocardial effect of estrogen was abolished by glibenclamide, which suggests that the cardioprotective effect of estrogen may result from activation of K(ATP) channels. In contrast, estrogen-induced attenuated vasoconstriction is associated with an attenuated release of endothelin-1, independent of K(ATP) activation.

Sex steroids in serum of prepubertal male and female horses and correlation with bone characteristics.

We used radioimmunoassay (RIA) to measure monthly serum levels of unconjugated and conjugated sex steroids (testosterone T, androstenedione A, estradiol E(2), and estrone E(1)) in 4 male and 4 female foals during their first year of life. Maximal production of sex steroids was detected from April to August with hormonal peaks, corresponding to the natural breeding season in adults. In males, only A levels were more steady. Total estrogens (unconjugated plus conjugated E(2) and E(1)) were the major steroids in immature males in contrast to adults. Estrogens generally peaked in young females before males; the major estrogen was E(1), and total estrogens overtook total androgens (unconjugated and conjugated T and unconjugated A). We also sampled 3 male and 3 female foals with bone alterations in adulthood. For all animals, serum levels of four bone formation markers were obtained: osteocalcin (O), hydroxyproline (HP), and alkaline phosphatase (AP), and a radiographic score was determined. Only male foals with normal skeletal frame (good radiographic score GRS) in adulthood showed a correlation (P < 0.01) between the distribution frequency of each bone formation marker and unconjugated E(2) or E(1) levels; this finding highlighted the role of unconjugated estrogens in bone maturation in horses, since this was not found in the groups with bone alterations. In females, the threshold of estrogen synthesis and sensitivity was probably sufficient to be a nonlimiting factor at this stage of development. Our results strongly suggest a differential regulation of the estrogen/androgen balance in horses according to sex, sexual maturation, and photoperiod. Moreover, estrogens appear to be crucial for skeletal development in male colts, and these steroids are good modulators of skeletal frame characteristics in adulthood.

Evaluation of single- and multiple-dose pharmacokinetics of synthetic conjugated estrogens, A (Cenestin) tablets: a slow-release estrogen replacement product.

A multiple-dose, placebo-controlled, randomized pharmacokinetic study was performed in 15 early (i.e., 1-3 years) postmenopausal women to evaluate the single and steady-state pharmacokinetics of 0.625 mg Cenestin (Synthetic Conjugated Estrogens, A) tablets, administered once daily for 90 days. Plasma concentration-time profiles for both total (conjugated and unconjugated) estrone and equilin, two major estrogens in Cenestin, were nearly superimposable between Day 1 (single dose) and Day 90 (multiple dose), indicating equivalent drug exposure from one dose to the next. For total estrone, the mean estimates of Cmax and AUC0-24 were 2.5 ng/ml and 35.0 ng x h/ml for Day 1 and 3.0 ng/ml and 39.8 ng x h/ml for Day 90, respectively. Similarly, Cmax and AUC0-24 mean values for total equilin were 1.4 ng/ml and 17.4 ng x h/ml after Day 1 and 1.5 ng/ml and 17.3 ng x h/ml after Day 90, respectively. The mean tmax value for total estrone was 8.3 hours on Day 1 and 8.6 hours on Day 90, indicating a slower rate of absorption. The average estimate for observed drug accumulation index for the 24-hour dosing interval was calculated to be 1.1 for total estrone and 1.0 for total equilin. These data, taken together, indicate a slow and steady rate of absorption, minimal drug accumulation at steady state, and consistent drug exposure between Cenestin doses.

The influence of maternal size on placental, fetal and postnatal growth in the horse. II. Endocrinology of pregnancy.

Within-breed artificial insemination and between-breed embryo transfer were carried out in small pony (P) and large Thoroughbred (Tb) mares to create 4 types of horse pregnancy in which the fetus experienced spatial and nutritional deprivation (Tb-in-P; n=8), luxury (P-in-Tb; n=7) or normality (Tb-in-Tb; n=7 and P-in-P; n=7) in utero. Measurement of equine chorionic gonadotrophin (eCG), total conjugated oestrogens and progestagen concentrations in serial peripheral serum samples recovered from all the mares throughout gestation showed that the amount of eCG produced during the first half of gestation was dependent upon the breed of the mare rather than the breed of the fetus being carried. In contrast, the mean total amounts of oestrogens produced, as measured by area under the curve, were significantly greater (P=0.003) in the two types of pregnancy in which a Thoroughbred fetus was being carried (Tb-in-Tb and Tb-in-P) than those in which a pony fetus was gestated (P-in-P and P-in-Tb); the evidence suggests that the Tb fetus may have larger gonads than the P fetus and thereby secrete more C-19 precursor steroids for aromatisation to oestrogens by the placenta. In the final weeks of pregnancy mean plasma progestagen concentrations rose much earlier, and to significantly higher levels (P<0.001), in the Tb-in-P than in the P-in-Tb pregnancies, thereby reflecting the increased fetal stress in the former causing premature maturation of the fetal adrenal gland. This, in turn, resulted in increased secretion of pregnenolone by the adrenal cortex for conversion to progestagens by the placenta.

A comparison of tibolone and hormone replacement therapy on coronary artery and myocardial function in ovariectomized atherosclerotic monkeys.

OBJECTIVE: Tibolone is used to prevent osteoporosis and to treat climacteric symptoms. The objectives of these studies were to measure and compare the effects of tibolone with hormone replacement therapy on coronary artery vascular reactivity and myocardial function and to relate these outcomes to treatment-induced plasma lipid/lipoprotein concentrations and atherosclerosis. DESIGN: One hundred forty-eight adult ovariectomized cynomolgus monkeys were fed an atherogenic diet for 24 months while receiving one of five oral treatments: no treatment (control, n = 31); conjugated equine estrogens (CEE), given at the equivalent of 0.625 mg/day ( n = 27); CEE (same dose) plus medroxyprogesterone acetate (MPA), given at the equivalent of 2.5 mg/day ( n = 29); low-dose tibolone (LoTib; 0.625 mg/day equivalent, n = 30); or high-dose tibolone (HiTib; 2.5 mg/day equivalent, n = 31). RESULTS: Quantitative coronary angiography showed that endothelium-mediated dilation was enhanced (17.5 +/- 5%, p = 0.002) in the CEE-treated group (but not other treatment groups) compared with the control. Both doses of tibolone and CEE reduced the incidence of dobutamine-induced ST-segment depression (LoTib: 33%, HiTib 25%, and CEE: 23%) compared to the control (79%) ( p = <0.05). Neither vascular reactivity nor dobutamine-induced myocardial ischemia were associated with treatment-induced changes in atherosclerosis or plasma lipid/lipoprotein concentrations. CONCLUSIONS: Tibolone, unlike CEE, has no benefit for endothelium-mediated dilation. Despite these differences, both tibolone and CEE reduced the incidence of myocardial ischemia, whereas CEE+MPA had no effect. It is speculated that tibolone may have direct effects on the myocardium that protect against myocardial ischemia.

The effects of six months of treatment with a low-dose of conjugated oestrogens in menopausal women.

OBJECTIVE: Hormone replacement therapy (HRT) is usually prescribed as medium- to high-dose formulations. Little is known, however, about dose-dependency of oestrogen effects on plasma hormone levels, markers of cardiovascular risk in lipid metabolism and the haemostatic system, or markers of bone turnover. SUBJECTS AND DESIGN: In an open trial, three groups of 12 or 13 healthy, non-obese postmenopausal women received conjugated equine oestrogens (CEE) for 6 months at doses of 0.3 mg/day (group 1), 0.6 mg/day (group 2) or 1.25 mg/day (group 3). From day 1 to day 10, CEE was administered alone, and from day 11 to day 21, in combination with 5 mg of medrogestone. Each treatment cycle was followed by a pause of 7 days. Fasting blood samples were obtained before treatment as well as on days 10, 21 and 28 of the first, third and sixth months on treatment. All results obtained on day 10 were grouped together as phase A, on day 21 as phase B, and on day 28 as phase C. MEASUREMENTS: Plasma concentrations of oestradiol (E), dehydroepiandrosterone sulphate (DHEA-S), total testosterone (T), FSH, PRL, sex hormone binding globulin (SHBG), type I procollagen propeptide (PICP) and the cross-linked carboxyterminal telopeptide of type I collagen (ICTP), total cholesterol, HDL-cholesterol, triglycerides (TG), apolipoprotein (apo) A-1, apo B, lipoprotein(a)[Lp (a)], fibrinogen, factor VIIc and plasminogen activator inhibitor 1 (PAI-1) were evaluated with commercially available kits. RESULTS: Dose-dependently, the three regimens increased E, SHBG and factor VIIc activity and decreased FSH, DHEAS, cholesterol, LDL-cholesterol and apoB. HDL-cholesterol and apoA-1 were slightly decreased in group 1 but increased in groups 2 and 3. The high CEE dosage in group 3 resulted in a significant increase of TG and decrease of Lp(a) and PAI-1. Markers of bone turnover were not significantly changed by any CEE dosage. CONCLUSIONS: Six months of treatment with 0.3 mg/day of conjugated equine oestrogen significantly lowers serum levels of total cholesterol and LDL-cholesterol without causing the adverse increases of triglycerides or factor VIIc, which were observed at higher doses. However, this low-dose treatment did not yield the maximal LDL-cholesterol lowering effect. Moreover, the positive effects of HRT on HDL-cholesterol, apolipoprotein A-I, lipoprotein (a) and plasminogen activator inhibitor-1 required at least the medium dose of 0.6 mg conjugated equine oestrogens per day. Therefore, further studies are needed to determine which dose of conjugated equine oestrogens has the optimal effect on cardiovascular risk and bone turnover.

Fecal estrone sulfate profile in sows during gestation.

The aim of this study was to establish radioimmunoassay (RIA) for fecal estrone sulfate (E1S) and to elucidate changes in fecal E1S during pregnancy in the sow. Fecal E1S was extracted on a commercially available solid phase column, and the E1S fraction obtained was subjected to RIA. The sensitivity of the RIA was 8.5 pg/tube. The intra- and inter-assay coefficients of variation were 8.8-8.9% and 10.7-14.2%, respectively. Mean recovery for E1S added to fecal samples was as high as 95.0%. A significant positive correlation (r = 0.904, n = 147 p < 0.0001) existed between fecal and plasma E1S concentrations. Mean E1S concentration in feces and plasma fluctuated exhibiting two peaks. The first peak of E1S concentration was evident on day 28-32 in feces and on days 26-30 in plasma. The E1S concentration in both feces and plasma remained at baseline levels during mid-pregnancy, but began to rise gradually around days 72-82 and 70-80, in feces and plasma respectively, and reached a peak concentration on days 110-114. Following parturition, the concentration of E1S in plasma declined rapidly, but there was a two-day delay before a decline in fecal E1S. Apart from this two-day delay, changes in fecal E1S were similar to those in plasma E1S. The study indicates that the measurement of E1S in feces could be a useful tool for early pregnancy diagnosis and for monitoring fetal development in sows and gilts.

Relationships of peri-partum, plasma concentrations of progesterone, oestrogens and 13,14-dihydro-15-ketoprostaglandin F2alpha in heifers and of anatomical measurements of dam and calf with difficulty of calving in early-bred Hereford x Friesian heifers.

Plasma concentrations of progesterone, oestradiol-17beta, oestrone, oestrone sulphate and PGFM have been measured daily during the first peri-partum period of 45 Hereford x Friesian heifers bred at 11 months of age. Anatomical measurements of dam and calf were also recorded. Twelve of the calvings were scored easy, 33 difficult. Each of five models (fitted by linear logistic regression) relating difficulty of calving to the hormonal and anatomical measurements, predicts with at least 94% accuracy the calving score (easy or difficult) among the calvings. The models predict that increases of progesterone concentration on the day before calving, of oestrone sulphate concentration on the day after calving and of heifer heart girth decrease the odds of difficult calving, whereas increases of heifer body length and of calf head circumference increase the odds of difficult calving.

Effect of conjugated estrogen on peripheral flow-mediated vasodilation in postmenopausal women.

Estrogen replacement protects against cardiovascular morbidity and mortality in postmenopausal women. Conjugated estrogen is the main hormone used in these studies. However, the vascular effects of this type of estrogen are, to a large extent, unexplored. The objective of this study was to evaluate short-term endothelium-dependent vascular effects of intravenously conjugated estrogen at 2 dose levels. Eleven postmenopausal women were included. Each study subject was given 2.5 and 5 mg of conjugated estrogen or placebo in random order with at least 1 week between each investigation in a double-blind study design. The vascular reactivity of the brachial artery was studied using the duplex technique before and 30 minutes after the intravenous administration of study drug. Reactive hyperemia was used to study the flow-mediated vasodilation. Serum estradiol increased significantly and dose dependently 5 minutes after conjugated estrogen infusion. The flow-mediated vasodilation at baseline before drug administration was 1.8 +/- 2.0% (mean +/- SD) after an average 400% increase in local blood flow. Conjugated estrogen at a dose of 2.5 mg caused an increase in flow-mediated vasodilation from 1.8 +/- 2.1% at baseline to 5.4 +/- 2.8% after infusion (p <0.05 vs placebo), whereas 5 mg caused an increase from 1.9 +/- 1.5% at baseline to 7.0 +/- 3.3% after infusion (p <0.05 vs placebo). Intravenous injection of conjugated estrogen significantly improves the peripheral vascular reactivity in postmenopausal women.

Estrogen diminishes postischemic hydroxyl radical production.

Reperfusion of blood flow to an ischemic myocardium is imperative to survival; ironically, it may also manifest several pathophysiological conditions. The most important of these are reperfusion arrhythmias and tissue injury and/or death. The mechanisms involved in reperfusion arrhythmias remain to be fully elucidated; however, increasing evidence indicates that reperfusion-induced arrhythmias are a free radical-mediated phenomenon. Acute administration of conjugated equine estrogen to dogs attenuates ischemia- and reperfusion-induced arrhythmias. The cardioprotective effect of estrogens in postmenopausal women is well documented, and recent studies suggest that estrogens possess strong antioxidant properties, with equine estrogens most potent. In this study we show that administration of conjugated equine estrogen to fully anesthetized dogs abolishes the burst of .OH radicals typically produced on reperfusion of the myocardium. This indicates that estrogen might attenuate reperfusion-induced ventricular arrhythmias by virtue of its antioxidant properties, suggesting a novel cardioprotective effect of the hormone.

Effects of age, season, and fertility status on plasma and intratesticular immunoreactive (IR) inhibin concentrations in stallions.

The nature of the relationship between inhibin and reproductive function in the stallion is yet to be elucidated. Blood and testes from 51 light horse stallions ranging in age from 2 mo to 25 years were collected during the breeding and nonbreeding seasons to study the effects of testicular maturation, aging, season, and fertility status on peripheral and intratesticular concentrations of Ir inhibin and other reproductive hormones. Of the 51 stallions, 12 age-matched stallions (6 fertile, 3 subfertile, and 3 infertile) were used in the fertility study. Blood samples were taken before castration and plasma stored at -20 degrees C for analysis of Ir inhibin, luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone (T), estradiol (E2), and estrogen conjugates (EC) by radioimmunoassay (RIA). Testes were homogenized and testicular extracts prepared and frozen at -70 degrees C for analysis of Ir inhibin, T, E2, and EC by RIA. Plasma concentrations of Ir inhibin, LH, FSH, T, E2, and EC and intratesticular concentrations of Ir inhibin, T, E2, and EC increased with age (P < 0.01). The most dramatic effect appeared to be during testicular maturation. An aging effect was not observed in adult stallions. A seasonal effect was not detected for any of the plasma hormones, whereas for the intratesticular hormones the only change noted was an increase in T in the nonbreeding season (P < 0.05). Plasma Ir inhibin, E2, and EC were lower (P < 0.01) and gonadotropins higher (P < 0.05) in infertile stallions. Plasma T levels did not change. Intratesticular Ir inhibin concentrations tended to be lower (P < 0.1) in subfertile stallions and significantly lower (P < 0.01) in infertile stallions, whereas intratesticular steroid levels were not different among the three groups. In conclusion, plasma and intratesticular Ir inhibin concentrations seem to be affected by testicular maturation and fertility status.

Comparison of the merits of measuring equine chorionic gonadotrophin (eCG) and blood and faecal concentrations of oestrone sulphate for determining the pregnancy status of miniature horses.

The relative merits of measuring blood concentrations of equine chorionic gonadotrophin (eCG, previously known as pregnant mare serum gonadotrophin (PMSG)), or oestrone sulphate (OS), or faecal OS concentrations for determining pregnancy status in miniature horses were investigated. Pregnant mares between 40 and 140 days after mating had serum eCG concentrations > 1 I.U. mL-1, with the highest concentrations occurring between days 50 and 120. However, eCG measurements were susceptible to returning a 'false positive' diagnosis of pregnancy. Plasma OS concentrations ranged from 0.1 to 3.6 ng mL-1 in non-pregnant mares, whereas pregnant mares beyond 100 days post-mating all had plasma OS concentrations > 30 ng mL-1. Faecal OS concentrations ranged from 4 to 89 ng g-1 in non-pregnant mares. For faecal samples collected from pregnant mares 150 days or more after mating, 97% of samples had OS concentrations > 85 ng g-1, the value 3 standard deviations above the mean non-pregnant value. None had values below 67 ng g-1, the value 2 standard deviations above the mean non-pregnant value. These results show that measurement of eCG is suitable for determining pregnancy status in miniature mares between 40 and 100 days post-mating. However, mares returning a 'pregnant' diagnosis should undergo a blood OS test 100 or more days after mating to eliminate the possibility of a 'false positive' diagnosis. Measuring blood OS is recommended as the method of choice for determining pregnancy status in miniature mares 100 or more days after mating. Faecal OS measurements provide a non-invasive alternative to blood OS testing from 150 days post-mating. However, the discrimination between 'pregnant' and 'non-pregnant' levels of OS is not as great in faeces as it is in blood.

Differential effect of carbamazepine and valproate monotherapy on plasma levels of oestrone sulphate and dehydroepiandrosterone sulphate in male epileptic patients.

Steroid sulphates such as oestrone sulphate (OE1S) and dehydroepiandrosterone sulphate (DHEAS) have been suggested to be of biological importance in different disease states such as breast cancer and atherosclerosis. Previous studies have shown that drugs such as aminoglutethimide and rifampicin that induce P450-dependent mixed-function oxygenases selectively suppress plasma OE1S levels. The aim of this study was to evaluate the influence of treatment with carbamazepine, an antiepileptic drug known to stimulate mixed-function oxygenases, on plasma levels of OE1S and DHEAS. We measured plasma OE1S and DHEAS together with other plasma oestrogens and androgens in male epileptic patients before and during carbamazepine monotherapy. Patients treated with valproate monotherapy acted as a control group. Treatment with carbamazepine decreased plasma OE1S levels from a mean value of 810.8 to 411.6 pmol/l (mean suppression to 50.7% of pretreatment levels, P < 0.001). Similarly, the ratio of OE1S to OE1 fell to 59.9% of pretreatment levels (P < 0.001)). DHEAS decreased from a mean level of 4.9 mumol/l before treatment to 3.0 mumol/l during carbamazepine therapy (mean reduction to 62.7% of pretreatment levels (P < 0.001), while the ratio of DHEAS to DHEA fell to 63.0% of pretreatment values (P < 0.01). No significant change in plasma levels of the other oestrogens or androgens measured was observed. Treatment with valproate caused a slight decrease in FSH levels (P < 0.05), but no change in any of the other hormones measured was observed. Studies are warranted to evaluate the possible effects of long-term treatment with carbamazepine on the risk of developing endocrine-sensitive tumours and cardiovascular disease and also the possible effects of alterations in plasma DHEAS on epileptic activity.