Circulating concentrations of hemostatic factors and two "steroid sensitive proteins" during oral hormone replacement therapy in women with coronary heart disease.

OBJECTIVE: To study a possible use of sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) as markers for changes in hemostatic factors during oral postmenopausal hormone replacement therapy (HRT). METHODS: Twenty-eight postmenopausal women were treated with oral conjugated equine estrogens+oral medroxyprogesterone acetate (CEE + MPA, n = 15) or with placebo (n = 13). Serum SHBG, CBG, testosterone, cortisol and plasma coagulation factors, coagulation inhibitors and markers of coagulation activation were measured before and after 6 and 12 months of treatment. RESULTS: Pretreatment plasminogen activator inhibitor 1 (PAI-1) levels correlated negatively to SHBG and antithrombin III (AT III) negatively to total and free cortisol. In the CEE + MPA group, CBG, SHBG and Factor VII increased, and PAI-1, AT III and free testosterone decreased during treatment. No significant changes were found in plasma von Willebrand factor antigen, thrombin-antithrombin complex, fibrin D-dimer and fibrinogen. A significant, negative correlation was found between changes in SHBG and PAI-1. No changes were found in the placebo group. CONCLUSION: The only correlation found between changes in "steroid sensitive" proteins and hemostatic factors was between increased SHBG and a possibly beneficial effect of estrogens, i.e. decreased PAI-1 values. SHBG or CBG could not be used as predictors of increased cardiovascular risk during postmenopausal oral HRT.

Immunohistochemical localization of glutaredoxin and thioredoxin in human endometrium: a possible association with pinopodes.

The human endometrium is only receptive for blastocyst implantation during a short period of the menstrual cycle. Pinopodes have been suggested to be markers of uterine receptivity, but little is known about their function and the biochemical processes taking place in them. In this study, we have examined the presence of glutaredoxin (Grx) and thioredoxin (Trx) and their co-localization with pinopodes in the normal human endometrium. Endometrial biopsies were obtained from fertile women with normal menstrual cycles. The biopsies were examined by scanning electron microscopy for detection of pinopodes and by immunohistochemistry for the expression of Grx and Trx. The pinopodes showed strong immunostaining for Grx. Increasing levels of Grx immunoreactivity were seen in the luminal and glandular epithelial cells concomitant with pinopode formation. Trx immunostaining was most intense in the ciliated cells of the luminal and glandular epithelium, while the staining was moderate to strong in a majority of the other cells, both epithelial and stromal. Trx levels did not change during the secretory phase of the cycle. The intense immunostaining concomitant with the presence of pinopodes suggests that Grx plays an important role during implantation, possibly by protecting the epithelial cells from apoptotic actions of the trophoblast cells.

The effect of 17beta-estradiol at doses of 0.5, 1 and 2 mg compared with placebo on early postmenopausal bone loss in hysterectomized women.

In a randomized double-masked placebo-controlled parallel-group trial 166 hysterectomized (+/- oophorectomy) perimenopausal and postmenopausal women aged 45-55 years with a follicle stimulating hormone level above 20 IU/l were treated with one daily dose of either 0.5 mg 17beta-estradiol (E2), 1 mg E2, 2 mg E2 or placebo for 2 years. Bone mineral density (BMD) and biochemical bone markers were determined. All three doses of E2 were significantly better than placebo with respect to change in BMD at the lumbar spine (L1-L4) (p<0.0001 for all pairwise comparisons) and hip (femoral neck, trochanter, Ward's triangle). The mean percentage change from baseline at the lumbar spine was -0.2%, 0.8% and 1.8% in the 0.5, 1 and 2 mg E2 groups respectively compared with -3.5% in the placebo group. Both 1 and 2 mg E2 were significantly better than placebo in increasing the BMD at the femoral neck (p<0.001), trochanter (p<0.01) and Ward's triangle (p<0.0001), while 0.5 mg E2 was significantly better than placebo at the femoral neck (p<0.001) and Ward's triangle (p<0.0001). The overall difference in mean percentage change in BMD at the femoral neck versus placebo (-0.2%) was 3.8% for 0.5 mg, 4.0% for 1 mg and 3.9% for 2 mg E2; the corresponding numbers for trochanter were 1.3%, 3.3% and 3.2%, respectively, and -2.2%,, 2.9, 2.9% and 4.0%, respectively, for Ward's triangle. More than half the women who received placebo presented with a decrease in BMD at the hip. The percentage of women in the 0.5 mg E2 group who maintained or increased BMD at the femoral neck, trochanter and Ward's triangle was 69%, 56% and 44%, respectively. For 1 mg E2 the numbers were 69%, 78% and 61% respectively, and for 2 mg E2 were 59%, 68% and 59% respectively. Osteocalcin, serum pyridinium crosslinks, urinary pyridinium cross-links and urinary hydroxyproline/creatinine decreased significantly (p<0.0001, p<0.05) in the 0.5, 1 and 2 mg E2 groups compared with the placebo group after 6 and 24 months of treatment.

Formation of pinopodes in human endometrium is associated with the concentrations of progesterone and progesterone receptors.

OBJECTIVE: To investigate the relation between the development of endometrial pinopodes and the serum concentration of hormones and the distribution of estrogen receptor-alpha, estrogen receptor-beta, progesterone receptor A, and progesterone receptor B. DESIGN: Prospective clinical study. SETTING: Hospital-based unit of reproductive health and university-affiliated reproductive research laboratories. PATIENT(S): Twenty-seven healthy fertile women with normal menstrual cycles. INTERVENTION(S): Urine and blood sampling for hormone measurement, vaginal ultrasonography, and endometrial biopsy. MAIN OUTCOME MEASURE(S): Appearance of the endometrium on light microscopy, pinopode formation, serum levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH), and expression of progesterone receptors A and B and estrogen receptors alpha and beta. RESULT(S): Pinopode formation and regression were closely associated with increases and decreases, respectively, in serum progesterone concentration. At pinopode development, levels progesterone receptors A and B in the glandular and luminal epithelial cells decreased; this effect was mainly dependent on the absence of progesterone receptor B. Serum estrogen levels and levels of estrogen receptor alpha and beta did not correlate with pinopode formation. CONCLUSION(S): The increase in serum progesterone level and down-regulation of progesterone receptor B are important in development of pinopodes.

Ovarian function during and after treatment with the new progestagen Org 30659.

OBJECTIVE: To evaluate ovarian function during 21 days of oral administration of different doses of Org 30659, a novel selective progestagenic steroid. DESIGN: Randomized, double-blind, dose-finding study. SETTINGS: Three centers in Austria, Sweden, and the United Kingdom. PARTICIPANTS: Eighty-one healthy women 19-40 years of age with regular ovulatory cycles. INTERVENTION: Daily oral administration of 0.060, 0.120, 0.180, or 0.240 mg of Org 30659, or 0.075 mg desogestrel (reference group), for 21 days. MAIN OUTCOME MEASURE(S): Once-daily measurements of follicular diameter and 17-beta estradiol, progesterone, FSH, and LH levels. RESULT(S): Daily treatment with Org 30659 for 21 days caused dose-dependent suppression of ovarian activity. No ovulation was observed in any study group. On average, ovulation returned 16.5 to 22.1 days after treatment. The effects of desogestrel, 0.075 mg, were similar to those of 0.060 and 0.120 mg of Org 30659. All doses were well tolerated, as shown by the type of side effects that occurred, the absence of an effect on physical and laboratory findings, and the low rate of study discontinuation. CONCLUSION(S): Daily oral administration of 0.060-0.240 mg of Org 30659 suppresses ovarian function to a level sufficient to inhibit ovulation. This effect is dose-dependent, and the suppressive effect is readily reversible at all doses tested. Org 30659 can thus be safely administered orally for 21 days to healthy female volunteers in a dosage of 0.060 mg/d to 0.240 mg/d.

The effect of tolterodine on the pharmacokinetics and pharmacodynamics of a combination oral contraceptive containing ethinyl estradiol and levonorgestrel.

BACKGROUND: Tolterodine is an antimuscarinic agent for the treatment of overactive bladder, a chronic condition that is particularly common in women. Given the prevalence pattern of overactive bladder and the widespread use of oral contraception, circumstances are likely to arise in which physicians may wish to prescribe tolterodine for patients already taking oral contraceptives. Based on a search of MEDLINE from 1990 to 2001, there have been no studies of whether concomitant use of these agents entails a risk of drug-drug interaction or conception. OBJECTIVE: This study investigated the effects of tolterodine on the pharmacokinetics and pharmacodynamics of a low-dose combination oral contraceptive (ethinyl estradiol 30 microg/levonorgestrel 150 microg). METHODS: This was an open-label, randomized, 2-period crossover study in healthy women. Oral contraception was given for 21 days either alone or in combination with oral tolterodine 2 mg BID (on days 1-14) over two 28-day contraceptive cycles. Pharmacokinetic assessments were performed on day 14 based on plasma levels of ethinyl estradiol and levonorgestrel up to 24 hours after dosing and serum tolterodine levels at 1 to 3 hours after dosing. The potential for pharmacodynamic interaction was assessed in terms of the risk of failure of suppression of ovulation based on serum levels of estradiol and progesterone measured throughout each cycle. RESULTS: Twenty-four healthy women (age, 23-41 years [mean, 30 years]; height, 155-178 cm [mean, 167 cm]; body weight, 51-75 kg [mean, 64 kg]) participated in the study. There was no evidence of a pharmacokinetic interaction between tolterodine and the steroid hormones in the oral contraceptive used, nor did the oral contraceptive show any relevant pharmacokinetic interaction with tolterodine. Serum levels of estradiol and progesterone indicated suppression of ovulation in both treatment periods. CONCLUSION: In this selected population. coadministration of tolterodine did not affect the contraceptive efficacy of a low-dose combination oral contraceptive containing ethinyl estradiol and levonorgestrel.

A randomized comparison of the effects on vaginal and cervical epithelium of a placebo vaginal ring with non-use of a ring.

Little is known about the effects of contraceptive vaginal rings on the vaginal surface epithelium, although most studies have not demonstrated any significant deleterious effect. However, one study found that some medium-to-long-term levonorgestrel-releasing ring users developed chronic erythematous and ulcerative lesions in the posterior vaginal fornix. Subsequently, this ring was completely redesigned (IVR-2) with different dimensions and much greater flexibility. The first version of IVR-2 was designed as a placebo ring to explore effects on the vagina and cervix without addition of a progestogen. One-hundred-sixty-six healthy sexually active women volunteers were recruited in four centers and randomly assigned for 6 months to either placebo ring use or control (non-use) using a predetermined randomization code generated by WHO in a 2:1 ratio. Careful inspections of the vaginal and cervical epithelium were performed with a colposcope at admission and at 2-month intervals. No clinically significant lesions were detected in any center either among ring users or controls. However, a number of minor changes in appearance of the vaginal and cervical epithelium (erythema, petechiae, ecchymosis, and minor aceto-white changes) were described from the Sydney Center, some of which were present on admission and some of which were found on subsequent examination. Ten of eleven "red" changes on the cervix and vagina were noted in IVR-2 users, and only one in the controls, suggesting a contribution by the IVR-2 to minor epithelial surface changes. Five of ten resolved completely with continued ring use. There was no correlation in this study between epithelial changes and cigarette smoking or frequency of intercourse in the 14 days prior to colposcopic examination but a significant relationship between tampon use in the last 7 days and all epithelial changes (p = 0.05) and especially red changes (p = 0. 027) was noted. Red changes were significantly less likely to be found among condom users (p = 0.007). The IVR-2 placebo ring did not produce clinically significant changes in the vaginal epithelium and cervical mucosa and a carefully controlled and randomized study should be considered to compare the epithelial appearances in women using a placebo IVR-2 and one releasing 20 microg levonorgestrel.

The influence of stress and state anxiety on the outcome of IVF-treatment: psychological and endocrinological assessment of Swedish women entering IVF-treatment.

BACKGROUND: Comparing stress levels in women entering IVF treatment with those of fertile controls as well as relating these levels to the outcome of IVF. METHODS: State anxiety and personality profiles as well as stress hormones were studied in 22 normally menstruating women entering IVF treatment for tubal infertility. Their personality profiles as well as state anxiety scores measured before entering IVF treatment were related to the outcome of treatment. Twenty-two fertile women served as controls. Stress markers were serum prolactin and cortisol. These were estimated by radioimmunoassay. The psychological evaluation included the Karolinska Scales of Personality (KSP) and state anxiety as measured by the STAI questionnaire. Basal FSH on cycle day 3 and E2 and P4 AUC during the luteal phase were evaluated as hormonal predictors for the outcome of IVF treatment. RESULTS: Comparison of the personality profiles of the two groups, showed that infertile women had significantly higher scores of suspicion (p>0.05), guilt (p>0.05), and hostility (p>0.01), but lower somatic anxiety (0.05) and indirect aggression (0.05) than fertile controls. The infertile women also had significantly higher levels of prolactin and cortisol throughout the menstrual cycle. Serum cortisol, prolactin and FSH levels on cycle day 3 did not differ between the women who conceived after IVF treatment and those who did not conceive. However, significant differences were found in E2 and P4 AUC (p>0.01) in the luteal phase between those women who became pregnant and those who failed. There was a trend (p<0.06) toward higher state anxiety levels among the women who did not succeed in becoming pregnant after IVF treatment. CONCLUSIONS: The main findings suggest that infertile women have a different personality profile in terms of more suspicion, guilt and hostility as compared to the fertile controls, perhaps as a response to their infertility. Their stress levels in terms of circulating prolactin and cortisol levels were elevated compared to the fertile controls. Psychological stress may affect the outcome of IVF treatment since state anxiety levels among those who did not achieve pregnancy were slightly higher than among those who became pregnant.

[Climacteric--medicalization, minimalization or normalization?]. / Klimakteriet--sjukligt, bagatelliserat eller normalt?

Women's experiences and ideas about the climacteric are not in accord with the biomedical model, in which the climacteric and the menopause are characterized as being a risk factor for various diseases and a cause of "estrogen deficiency", a hormonal disease which is assumed to persist during the rest of life. The biomedical model may lead to medicalization and pathologizing, increasing the subordination of women and making them dependent on the health care system. Women who use hormonal therapy during the climacteric have many characteristics differentiating them from women who do not use such therapy. Thus, epidemiological studies will be difficult to interpret with respect to the long term effects of hormonal therapy. It is argued that the consultation for women of middle-age should be characterized by a holistic view of the woman taking account of her gender identity, life conditions and life situation. Such a view should focus on the woman's own ideas as to diagnostic procedures, treatment and solutions. In view of the lack of knowledge about the pros and cons of hormonal therapy, women themselves should make the decision, and such decisions should be encouraged. Also, the efforts directed towards women's compliance to hormonal therapy can be questioned. Women's climacteric symptoms should neither be medicalized, pathologized or minimized.

Bioavailability of norethisterone acetate alone and in combination with estradiol administered in single or multiple oral doses to postmenopausal women.

OBJECTIVES: Twenty-four postmenopausal women were randomly allocated to a cross-over trial for an investigation of the pharmacokinetics of norethisterone acetate (NETA; 0.5 mg), administered alone or in combination with estradiol (E2; 1 mg), both after a single oral dose. In a second trial, the above combination of 0.5 mg NETA with 1 mg E2 was administered daily for 28 days. METHODS: Plasma levels of NET, E2, estrone (E1) and estrone sulphate fraction containing an admixture of estrone glucuronide (E1S/E1G) were measured by radioimmunoassay at various intervals up to 72 h in the first trial and at the same intervals after the 28th day in the second trial. RESULTS: In the first, single-dose trial, pharmacokinetic parameters of NET were similar for NETA administered alone and its combination with E2. There was no statistically significant difference in the area under curve values AUC0-24 and AUC0-infinity and no apparent major differences were observed for other pharmacokinetic parameters. No carry-over effects due to the cross-over design were seen. The multiple dosage in the second trial did not cause any major changes in the pharmacokinetic parameters of NET, except for the AUC0-24 and AUC0-infinity values which were significantly higher than those seen in the first trial. The levels of E2 exhibited, shortly after the intake of E2, a rapid burst. The levels gradually decreased to a nadir followed by an increase to the main peak and by the subsequent elimination phase. The difference between the peak and nadir levels was significant (P < 0.05) in the second, multiple-dose trial. This bimodal pattern was not observed in earlier studies. The main metabolite of E2 was E1S/E1G, followed by E1, as could be seen from the AUC0-infinity values. These were, in both trials, approximately 300 and 7-times higher for the E1S/E1G and E1, respectively, than those for E2. For all analytes, the AUC0-24 values were significantly higher in the second trial than those found in the first trial, indicating accumulation upon repeated administration. Pharmacokinetics of all analytes remained linear in the second trial, as follows from the statistically established equality of AUC0-24 found in the second, multiple-dose trial with AUC0-infinity in the first, single-dose trial. The absorption half-life and t-max values of E1S/E1G appeared to be considerably shorter than those of E1 in both trials. CONCLUSIONS: The bioavailability of NET was not influenced by its combination with 1 mg E2. The most abundant metabolite of E2 was the E1S/E1G fraction, which may have served as the main source of E2 and other estrogens due to metabolic interconversions during the absorption and elimination phases.

A randomized trial on effects of hormone therapy on ambulatory blood pressure and lipoprotein levels in women with coronary artery disease.

OBJECTIVE: To investigate 1-year effects of hormone replacement therapy (HRT) on ambulatory blood pressure (ABP) and lipoprotein levels in postmenopausal women with coronary artery disease (CAD). METHODS: Sixty patients at a mean age (+/- SD) of 59 +/- 7 years were randomized into three groups: conjugated equine oestrogens (CEE) 0.625 mg daily (n = 20), 50 microg 17beta-oestradiol transdermally (TTSE) per 24 h (n = 20) or placebo (n = 20) for 18 days, then combined with medroxyprogesterone acetate 5 mg for 10 days. Each cycle of 28 days was repeated for one year. RESULTS: Night-time systolic ABP had decreased by 9.6% (P= 0.0075) in 15 of 18 women in the CEE group and by 22% in 12 of 13 women (P = 0.0034) in the placebo group after 1 year. In the CEE group, a 4.6% rise in daytime systolic ABP (P< 0.05) and a 4.2% rise in night-time systolic ABP (P< 0.05) appeared from baseline to 6 months in 13 of 18 women. In the CEE group (14 women analysed), high-density lipoprotein levels showed a 15.8% increase (P= 0.0018) in 13 women, low-density lipoprotein levels a 15.2% decrease (P= 0.0129) in 12 women and total cholesterol levels a 7.5% decrease (P = 0.057) in 11 women after 1 year. Triglyceride levels showed no changes. In the TTSE group and in the placebo group, with 12 and 13 women analysed respectively, no significant changes appeared. CONCLUSIONS: One year of HRT in patients with CAD does not influence ABP. Oral HRT induces beneficial effects on lipoprotein levels.

Endometrial evaluation is not predictive for in vitro fertilization treatment.

PURPOSE: The main purpose of this study was to evaluate ovarian function by clomiphene citrate (CC) challenge test in a group of tubal infertile women and to study endometrial morphological maturation in the early luteal phase of CC-stimulated cycles as compared to in vitro fertilization (IVF) treatment outcome. METHODS AND RESULTS: Four women presented with strongly retarded, proliferative endometrium in the luteal phase. Of these, three presented with impaired ovarian function, high basal follicle-stimulating hormone, and high follicle-stimulating hormone levels after clomiphene stimulation on cycle day 10. In the remaining 30 women, showing an in-phase endometrium after CC stimulation, a comparison of six morphological characteristics did not reveal any significant differences between the 14 women who did become pregnant and the 16 who did not. No significant differences in endometrial thickness were observed between the groups. Significant differences were found when comparing estradiol and progesterone area under the curve during the luteal phase (P < 0.001 and P < 0.01, respectively) between those who did and those who did not become pregnant. CONCLUSIONS: Luteal endometrium morphology was not a sharp instrument to detect differences between women who did and women who did not become pregnant following IVF treatment, while ovarian function, as measured by hormonal markers, seemed to be a more reliable prognostic factor for IVF treatment outcome.

Female patients with cystic fibrosis suffer from reproductive endocrinological disorders despite good clinical status.

Ten women with cystic fibrosis (CF) were evaluated with regard to hormonal profiles during a natural and a clomiphene citrate (CC) stimulated cycle. Five of the women were found to be anovulatory during a natural cycle. All women except one did respond with ovulation to CC stimulation indicating adequate ovarian response. Neither did they show increased follicle-stimulating hormone (FSH) concentrations on day 10 after CC treatment confirming normal ovarian reserve. Clinically the anovulatory women differed from the ovulating in two aspects: more profound essential fatty acid deficiency (EFAD) and higher peak/basal insulin response during an oral glucose tolerance test. The anovulatory women had significantly lower luteal oestradiol and progesterone but higher total testosterone concentrations when compared to healthy controls and the ovulatory CF women. The pathological insulin response and high testosterone concentrations resemble those seen in women with polycystic ovarian (PCO) syndrome. However, the CF patients in our study had normal ovaries, as deduced from ultrasound examination and normal luteinizing hormone (LH)/FSH ratio. It is suggested that EFAD as well as hypersecretion of insulin may be of importance for the observed ovarian dysfunction. Further studies are needed to evaluate the relation between ovulatory mechanisms and EFAD in CF women as well as studies to compare anovulatory CF women with women with PCO syndrome.

Does sublingual 17 beta-oestradiol have any effects on exercise capacity and myocardial ischaemia in post-menopausal women with stable coronary artery disease?

BACKGROUND: A variety of vascular effects have been ascribed to 17 beta-oestradiol. These effects may partially explain the reduced incidence of cardiovascular disease found in post-menopausal women on oestrogen replacement therapy. OBJECTIVES: To evaluate the effects of 2 mg sublingual 17 beta-oestradiol on exercise capacity, exercise-induced myocardial ischaemia and circulating levels of endothelin-1 in post-menopausal women with stable coronary artery disease. METHODS: Twelve post-menopausal women, mean age 61 (range 52-72) years, with angiographically verified significant coronary artery disease, were randomly assigned to 2 mg of sublingual 17 beta-oestradiol, 2.5 mg of buccal nitroglycerine and to placebo in a double-blind cross-over study design with at least 2 days between each of the study arms. Antianginal medications, with the exception of beta-blockers, were discontinued before investigation. All study patients underwent a maximal bicycle exercise test 30 min after drug intake. Blood was withdrawn immediately before and up to 8 h after medication for analyses of circulating levels of oestradiol and endothelin-1. RESULTS: The mean serum levels of oestradiol increased from a control level of 72 +/- 28 pmol.l-1 to 3557 +/- 1731 pmol.l-1 after 30 min and to 5028 +/- 3971 pmol.l-1 after 60 min with a gradual decline thereafter. Sublingual 17 beta-oestradiol did not induce any improvement in exercise duration when compared with nitroglycerin and placebo (500 +/- 112 s, 505 +/- 107 s, 498 +/- 157 s), and did not influence time to onset of ST-segment depression (358 +/- 89 s, 436 +/- 93 s, 384 +/- 116 s). The plasma levels of endothelin-1 did not change after administration of 17 beta-oestradiol, nitroglycerin or placebo. CONCLUSIONS: No effects of exercise capacity, exercise-induced acute ischaemia, or plasma levels of endothelin-1 were found after a single dose of 2 mg 17 beta-oestradiol in post-menopausal women with documented coronary artery disease.

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.

Long-term effects of hormone replacement therapy on symptoms of angina pectoris, quality of life and compliance in women with coronary artery disease.

OBJECTIVE: The aim of the present study was to evaluate the effects of HRT on symptoms of angina pectoris, quality of life and factors of importance for compliance in women with ischemic heart disease. METHODS: Sixty postmenopausal women with coronary artery disease were randomized into three groups: one group received transdermal 17 beta-estradiol at a dose of 50 micrograms per 24 h alone for 18 days followed by 10 days of combined treatment with medroxyprogesterone acetate (MPA) 5 mg orally; the second group received placebo and the third group received conjugated estrogens orally for 18 days followed by a combined treatment with MPA for 10 days. Clinical evaluations were performed at baseline, after 3, 6 and 12 months. The investigations included gynecological history. occurrence of climacteric symptoms, quality of life evaluation, cardiac history and symptoms of angina pectoris. RESULTS: Forty-six women (77%) completed the study during 1 year. The following cardiac events occurred in the women who completed the study: one patient was hospitalized because of congestive heart failure (patch), two patients because of angina pectoris, one patient because of coronary bypass operation (CEE) and three patients underwent balloon dilatation (placebo), all three on CEE. Among the 14 women who discontinued, two patients had TIA (patch), one experienced palpitations (CEE) and one woman died from myocardial infarction (placebo). Overall improvement in mood and cognitive functions were reported in all three treatment groups. CONCLUSIONS: HRT does not seem to have negative effects on symptoms of angina pectoris and seems to increase quality of life in older women with coronary heart disease. It also seems safe from the cardiovascular point of view.

The use of a sensitive equilibrium dialysis method for the measurement of free testosterone levels in healthy, cycling women and in human immunodeficiency virus-infected women.

Measurements of total and free testosterone levels in women have lacked precision and accuracy because of limited assay sensitivity. The paucity of normative data on total and free testosterone levels in healthy women has confounded interpretation of androgen levels in women with human immunodeficiency virus (HIV) infection and other disease states. Therefore, the objectives of this study were to develop sensitive assays for the measurement of the low total and free testosterone levels in women to define the range for these hormones during the normal menstrual cycle and assess the total and free testosterone levels in HIV-infected women. By using a larger volume of serum, increasing the incubation time, and reducing the antibody concentration, the sensitivity of the total testosterone assay was increased to 0.008 nmol/L, and that of the free testosterone assay was increased to 2 pmol/L. The mean percent free testosterone was 1.0 +/- 0.1% of the total testosterone. Serum total and free testosterone levels in the follicular and luteal phases were not significantly different, but both demonstrated a modest preovulatory increase, 3 days before the LH peak. Serum total [0.50 +/- 0.32 (14.60 +/- 9.22) vs. 1.2 +/- 0.7 nmol/L (34.3 +/- 21.0 ng/dL); P < 0.0001] and free testosterone levels (5.56 +/- 2.70 (1.58 +/- 0.80) vs. 12.8 +/- 5.5 pmol/L (3.4 +/- 1.7 pg/mL); P < 0.0001) were significantly lower in HIV-infected women (n = 37) than in healthy women (n = 34). Serum total and free testosterone levels were also significantly lower in HIV-infected women who were menstruating normally. There were no significant differences in serum total and free testosterone levels between those who had lost weight and those who had not. Testosterone levels correlated inversely with plasma HIV ribonucleic acid copy number. Serum FSH, but not LH, levels were significantly higher in HIV-infected women than in controls. Using assays with sufficient sensitivity, we defined the range for total and free testosterone levels during the normal menstrual cycle. Serum total and free testosterone levels are lower in HIV-infected women and correlate inversely with plasma HIV ribonucleic acid levels. The hypothesis that androgen deficiency contributes to wasting in HIV-infected women remains to be tested.

Importance of endometrial quality in women with tubal infertility during a natural menstrual cycle for the outcome of IVF treatment.

PURPOSE: The importance of endometrial maturation at estimated time of implantation for the outcome of IVF treatment in regularly menstruating women with tubal infertility was evaluated. METHODS: FSH was measured on cycle day 3, on days 10-15 urine and blood were collected to estimate the day of the LH peak, and E2 and P4 were measured during the luteal phase, on cycle days 19-26. An endometrial biopsy was obtained on days LH + 3 to LH + 6. RESULTS: The number of subjects with delayed endometrial maturation was larger in the group of infertile women who did not become pregnant compared to pregnant women and controls. Those infertile women who did not become pregnant after IVF treatment also presented with a higher basal FSH on cycle day 3 and lower E2 and P4 AUC in the luteal phase. Six infertile women and two controls presented with mid- and late-proliferative endometrium in the luteal phase on cycle days LH + 3 to LH + 6, in the presence of adequate E2 and P4 secretion. Six morphological characteristics were compared in the three groups: (1) 17 infertile women who became pregnant, (2) 18 who did not become pregnant, and (3) 28 controls. The pregnant infertile women did not differ from the controls. The numbers of glandular and stromal mitoses were significantly higher in those women who did not become pregnant (P < 0.01) compared with those who became pregnant. Endometrial biopsies obtained on cycle days LH + 5 and LH + 6 showed significant differences in glandular epithelial height (P < 0.05) and number of vacuolated cells among the nonpregnant women (P < 0.01), the pregnant women (P < 0.05), and controls. CONCLUSIONS: A higher frequency of retarded endometrial development in women who did not become pregnant following IVF treatment was found. In some cases, endometrial insensitivity could most likely cause retarded endometrial development and failure of implantation after IVF treatment, which could not be overcome by routine luteal-phase support. However, our results do not allow conclusions concerning its relative importance compared to preembryo quality; this has to be investigated further.

Psychosocial factors associated with the use of hormonal replacement therapy in a longitudinal follow-up of Swedish women.

OBJECTIVES: To follow up a cohort of 1400 women aged 52 years who had replied to a health questionnaire 4 years previously. The follow-up covered general and gynecological health, experience of symptoms, the use of hormone replacement, the reasons for starting HRT and effectiveness of treatment as well as comparison of users and nonusers concerning psychosocial factors and life style. METHODS: A questionnaire together with a letter was mailed to the women who had responded previously. The questionnaire covered four different areas: sociodemographic background, general and gynecological health, a 20-item symptom rating scale, and questions concerning work role. RESULTS: A total of 1194 women (85%) responded to the questionnaire; 40% of the women were currently using hormone replacement. The reasons for starting treatment were: relief of somatic (55%) and psychological symptoms (20%), increased wellbeing (5%), to prevent disease (5%) and other reasons, such as keeping young (15%). Positive effects were experienced by 86% and negative effects by 26%. Women using HRT had less frequent vasomotor symptoms, sleep problems and vaginal dryness and were more harmonious than nonusers. There were no differences between HRT users and nonusers regarding negative mood and sexual desire. Women with psychologically demanding and stressful jobs requiring concentration were more likely to use hormone replacement. CONCLUSIONS: Swedish women are increasingly willing to start hormone replacement, particularly those who suffer from vasomotor symptoms and who have stressful and psychologically demanding occupations. The majority of these experience relief of symptoms. A certain proportion will suffer from side effects and are likely to discontinue treatment.