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There are conflicting data on postmenopausal hormone therapy (HT) and the risk of vascular dementia (VD) and Alzheimer's disease (AD).

Context:The “window of opportunity hypothesis” refers to data indicating that conjugated equine estrogen alone or in combination with medroxyprogesterone acetate, if initiated before 60 years of age, protects the heart but endangers it if initiated later (Women's Health Initiative study). Less is known about the “window of opportunity hypothesis” with natural estradiol alone (ET) or with various progestins in combination with estradiol (EPT).Objective:We related the death risk from coronary heart disease (CHD) in users of ET or EPT to the age at the initiation of therapy and to the progestin component of EPT.Design, Patients, Interventions, and Main Outcome Measures:Altogether, 498 105 women had used ET or EPT containing medroxyprogesterone acetate, norethisterone acetate, dydrogesterone, other progestins, or tibolone during 3.7 million person-years during 1994–2009. Women were followed from the therapy initiation to death, or to the end of year 2009. The risk of CHD death in hormone users was compared with that in the age-matched background population using standardized mortality ratio with 95% confidence intervals.Results:Age younger than 60 rather than older than 60 years at the initiation of ET (standardized mortality ratio, 0.53; 95% confidence interval, 0.47–0.59 vs 0.76; 0.71–0.82), EPT with norethisterone acetate (0.45; 0.41–0.49 vs 0.74; 0.67–0.81), or tibolone (0.35; 0.26–0.47 vs 1.01; 0.67–1.46) therapy lasting for less than 5 years was associated with significantly greater decreases in the CHD death risk. A similar tendency was also seen for other EPT groups and for longer use. In all hormone users, the CHD death risk was smaller the earlier the use of ET or EPT had started (P< .05); this phenomenon was unrelated to the progestin component of EPT.Conclusions:Estradiol-based hormone therapies are accompanied with larger CHD mortality risk reductions the earlier the therapies are initiated. The progestin component of EPT does not modify this “timing effect.”

Context:Current guidelines recommend annual discontinuation of postmenopausal hormone therapy (HT) to evaluate whether a woman could manage without the treatment. The impact of HT on cardiovascular health has been widely studied, but it is not known how the withdrawal of HT affects cardiovascular risk.Objective:We evaluated the risk of cardiac or stroke death after the discontinuation of HT.Design, Patients, Interventions, and Main Outcome Measures:Altogether 332 202 Finnish women discontinuing HT between 1994 and 2009 (data from National Reimbursement register) were followed up from the discontinuation date to death due to cardiac cause (n = 3177) or stroke (n = 1952), or to the end of 2009. The deaths, retrieved from the national Cause of Death Register, were compared with the expected number of deaths in the age-standardized background population. In a subanalysis we also compared HT stoppers with HT users.Results:Within the first posttreatment year, the risk of cardiac death was significantly elevated (standardized mortality ratio; 95% confidence interval 1.26; 1.16–1.37), whereas follow-up for longer than 1 year was accompanied with a reduction (0.75; 0.72–0.78). The risk of stroke death in the first posttreatment year was increased (1.63; 1.47–1.79), but follow-up for longer than 1 year was accompanied with a reduced risk (0.89; 0.85–0.94). The cardiac (2.30; 2.12–2.50) and stroke (2.52; 2.28–2.77) death risk elevations were even higher when compared with HT users. In women who discontinued HT at age younger than 60 years, but not in women aged 60 years or older, the cardiac mortality risk was elevated (1.94; 1.51–2.48).Conclusions:Increased cardiovascular death risks question the safety of annual HT discontinuation practice to evaluate whether a woman could manage without HT.

Because premenstrual symptoms in fertile age resemble menopausal symptoms, many women with premenstrual symptoms fear that they have an increased risk for developing vasomotor symptoms in menopause. We investigated the impact of premenstrual symptoms on the occurrence and severity of menopausal vasomotor symptoms and quality of life.

We assessed the impact of hot flashes and various forms of hormone therapy on health-related quality of life and sexual well-being in recently postmenopausal women.

Recent data have indicated that menopausal hot flashes may be a determinant for cardiovascular health. Therefore, we studied the impact of hot flashes on insulin resistance, one of the most powerful markers of cardiovascular health, in recently postmenopausal women.

The aim of the study was to compare the responses of heart rate variability (HRV) with hormone therapy in recently postmenopausal women with and without vasomotor hot flashes.

The aim of this study was to investigate whether cardiovascular autonomic reactivity and risk profile are associated with the frequency and severity of hot flashes in recently postmenopausal women.

Menopausal hot flashes may affect vascular function and perhaps explain conflicting data on cardiovascular disease (CVD) between observational and randomized hormone therapy (HT) studies. We prospectively assessed hot flash status in recently postmenopausal women and related it to a number of biochemical vascular surrogate markers for CVD.

Isoflavones may display beneficial health effects in postmenopausal women. We studied in a clinical trial whether isolated isoflavone treatment in postmenopausal women could affect reverse cholesterol transport as evaluated by adenosine triphosphate-binding cassette A1- (ABCA1), dependent cholesterol efflux from macrophages. In addition, various serum lipid and lipoprotein parameters were investigated. Furthermore, we separately assessed equol-producing and non-equol-producing women.

Ospemifene is a novel selective estrogen receptor modulator (SERM) that is initially being developed for the treatment of vaginal atrophy in postmenopausal women. However, it also shows promise in the prevention and treatment of osteoporosis. As a part of a phase II trial, we compared the effects of ospemifene and raloxifene on bone turnover in postmenopausal women. The study was conducted as a randomized, double-blind study in which 118 healthy postmenopausal women received 30 (n= 29), 60 (n= 30), or 90 mg (n= 30) ospemifene or 60 mg (n= 29) raloxifene for 3 months. Bone resorption was assessed by measuring the urinary outputs of N- and C-terminal cross-linking telopeptides of type I collagen (NTX and CTX, respectively). Bone formation was assessed by measuring bone-specific alkaline phosphatase (bone ALP), osteocalcin (OC), procollagen type I N propeptide (PINP), and procollagen type I C propeptide (PICP) in serum. All markers were studied before and at 3 months and 2–4 weeks after cessation of the medication. Urine NTX outputs decreased in all study groups, and the only statistically significant difference in NTX was observed between raloxifene and 30 mg ospemifene, which was reduced more in the raloxifene group. The output of CTX decreased most clearly in 60- and 90-mg ospemifene groups, but no significant differences between study groups emerged. A significant difference was found between the 90-mg ospemifene group and raloxifene in PINP in favor of ospemifene. No other differences in bone formation markers emerged between ospemifene and raloxifene. The study confirms the bone-restoring activity of ospemifene, which is comparable to that of raloxifene.

Based on the low cardiovascular risk in Asian populations, phytoestrogens are believed to provide vascular benefits. To elucidate the mechanisms behind the possible cardiovascular effects of phytoestrogens, we evaluated reverse cholesterol transport by assessing the capacity of serum to promote cholesterol efflux in postmenopausal women treated with isolated isoflavones.

Objective:Adiponectin is an adipocyte-derived protein with profound insulin-sensizing, anti-inflammatory, and antiatherogenic effect. Surprisingly, recent evidence suggests that adiponectin concentrations are increased during preeclampsia, which is characterized by insulin resistance. We studied whether serum adiponectin is related to insulin sensitivity in preeclamptic and normotensive pregnant women.Methods:We measured serum adiponectin concentrations and insulin sensitivity (intravenous glucose tolerance test/minimal model) in 22 women with preeclampsia and 15 normotensive controls with similar pre-pregnancy body mass index (BMI) (range 18-29 kg/m2) between 29 and 39 weeks of gestation. Fourteen cases and 10 controls were also studied 6-22 weeks after delivery. No subject had gestational diabetes.Results:During pregnancy, the mean adiponectin concentration in preeclamptic women was 10.3 (SD 4.2) μg/mL as compared to 7.9 (SD 2.9) μg/mL in normotensive controls (95% confidence interval [CI] for difference 0.1-5.3 μg/mL; P = .04). Adiponectin concentrations were unrelated to insulin sensitivity both in preeclamptic and normotensive subjects; insulin sensitivity was decreased in preeclampsia (P = .01). After delivery, mean adiponectin concentration was lower than during pregnancy: 7.4 (SD 3.0) μg/mL in preeclamptic subjects (P = .001) and 7.1 (SD 1.6) μg/mL in normotensive controls (P = .06) and similar in cases and controls (95% CI for difference - 1.7-2.3 μg/mL, P = .7).Conclusions:Despite their reduced insulin sensitivity, preeclamptic women have higher adiponectin concentrations than normotensive pregnant women. These concentrations are unrelated to insulin sensitivity. After pregnancy, the difference in adiponectin concentrations is no longer present between the two groups. These findings are consistent with a role of adiponectin in the pathophysiology of preeclampsia.

Objective: Adiponectin is an adipocyte-derived protein with profound insulin-sensitizing, antiinflammatory, and antiatherogenic effects. Surprisingly, recent evidence suggests that adiponectin concentrations are increased during preeclampsia, which is characterized by insulin resistance. We studied whether serum adiponectin is related to insulin sensitivity in preeclamptic and normotensive pregnant women. Methods: We measured serum adiponectin concentrations and insulin sensitivity (intravenous glucose tolerance test/minimal model) in 22 women with preeclampsia and 15 normotensive controls with similar pre-pregnancy body mass index (BMI) (range 18–29 kg/m2) between 29 and 39 weeks of gestation. Fourteen cases and 10 controls were also studied 6—22 weeks after delivery. No subject had gestational diabetes. Results: During pregnancy, the mean adiponectin concentration in preeclamptic women was 10.3 (SD 4.2) Lg/mL as compared to 7.9 (SD 2.9) Lg/mL in normotensive controls (95% confidence interval [CI] for difference 0.1—5.3 Lg/mL; P =.04). Adiponectin concentrations were unrelated to insulin sensitivity both in preeclamptic and normotensive subjects; insulin sensitivity was decreased in preeclampsia (P=.01). After delivery, mean adiponectin concentration was lower than during pregnancy: 7.4 (SD 3.0) Lg/mL in preeclamptic subjects (P =.001) and 7.1 (SD 1.6) µg/mL in normotensive controls (P=. 06) and similar in cases and controls (95% CI for difference —1.7—2.3 µg/mL, P=.7). Conclusions: Despite their reduced insulin sensitivity, preeclamptic women have higher adiponectin concentrations than normotensive pregnant women. These concentrations are unrelated to insulin sensitivity. After pregnancy, the difference in adiponectin concentrations is no longer present between the two groups. These findings are consistent with a role of adiponectin in the pathophysiology of preeclampsia.

To compare ospemifene and raloxifene regarding their effects on hormones, lipids, genital tract, and tolerability in postmenopausal women.

Ospemifene, a novel selective estrogen receptor modulator (SERM), shows promise for bone preservation in postmenopausal women. This study examined the effects of ospemifene on different vascular surrogate markers.

Ospemifene, a novel selective estrogen receptor modulator, shows a potential for prevention and treatment of osteoporosis in postmenopausal women. We studied the effects of ospemifene on hormone levels, genital tract organs, climacteric symptoms, and quality of life.

Misoprostol is widely used in combination with mifepristone for medical termination of pregnancy. We studied the endocrine parameters of trophoblast function during medical termination of early pregnancy using mifepristone in combination with oral or vaginal misoprostol. The effect of prolonged misoprostol administration was also examined.

To evaluate C to T substitution at nucleotide 677 of N5,N10-methylenetetrahydrofolate reductase gene in women with prior preeclamptic or normotensive pregnancies.

To examine whether depression and anxiety in early pregnancy are associated with preeclampsia in an unselected nulliparous population.

Objective: To evaluate C to T substitution at nucleotide 677 of N5, N10-methylenetetrahydrofolate reductase gene in women with prior preeclamptic or normotensive pregnancies.

Objective: To examine whether depression and anxiety in early pregnancy are associated with preeclampsia in an unselected nulliparous population.

Objective: To identify factors associated with fear of childbirth during and after first labor.

Objective: To study the isoforms of insulin-like growth factor binding protein-1 (IGFBP-1) in cervical secretion and to evaluate whether their assessment could serve in prediction of cervical ripeness at term.

Objective: To study the plasma levels of homocysteine in preeclampsia and relate them to insulin sensitivity.

Objective: To clarify production of nitric oxide with preeclampsia.

To study the plasma levels of homocysteine in preeclampsia and relate them to insulin sensitivity.

To study the isoforms of insulin-like growth factor binding protein-1 (IGFBP-1) in cervical secretion and to evaluate whether their assessment could serve in prediction of cervical ripeness at term.

Objective To assess the possible role of serum levels of activin A, inhibin A and pro‐αC inhibin (pro‐Design αC) in insulin sensitivity in pre‐eclampsia.

The effects of suprapubic Marshall-Marchetti-Krantz (MMK) operation or vaginal Kelly's operation on roentgenographic anatomy of the lower urinary tract were elucidated by means of chain urethrocystography (UCG). A selected series of 30 postoperatively continent and 70 incontinent patients were examined both preoperatively and 3-4 years after operation.Both the urethral inclination (UI) and the posterior urethrovesical (PUV) angle decreased after the operation. The decrease was more marked after successful than unsuccessful operations. The MMK operation reduced the UI and the PUV angle significantly more than did Kelly's operation in both successful and unsuccessful cases. The position of the bladder base or the PUV junction was not altered significantly by either of the operations, whether successful or unsuccessful. The patients with postoperative detrusor instability had roentgen-anatomical findings similar to those of continent patients.

Objective: Labetalol reduces blood pressure primarily by blocking alpha-and beta-receptors, but other mechanisms of action may also be possible. We studied the effects of labetalol on the synthesis of vasodilatory prostacyclin (PGI2) and vasoconstrictory endothelin-1 (ET-1) by cultured human umbilical vein endothelial cells (HUVECs). We also studied the effect of oral labetalol treatment on PGI, and thromboxane A2 (TxA.2) production in preeclamptic patients.Methods: HUVECs were incubated in the absence (control) and presence of labetalol (10-8-10-5 mol/L) and the release of PGI-, as measured by its metabolite 6-keto-PGF1α, and that of ET-1, were assessed by radioimmuno- assays. Because the presence of serum strongly affects endothelial cell function, we studied the effect of labetalol in HUVECs incubated with or without serum. In the in vivo part of the study, urine samples collected before and during oral labetalol intake were assessed for 2,3-dinor-6-keto-PGF, a metab-olite of PGI.1α and for 2,3-dinor-thromboxane-B., a metabolite of TxA,2 with high-pressure liquid chromatography and radioimmunoassay.Results: HUVECs incubated in the presence of serum (10%) produced 8 times more 6-keto-PGFloi and 5 times more ET-1 than HUVECs incubated without serum. Labetalol (10-8-10-5 mol/L) did not affect the production of PGL, although the highest labetalol level (not achievable in vivo, 10-5 mol/L) was accompanied by a drop in PG1-, release in both serum-free (- 21%) and serum conditions (- 14%); this was probably a sign of toxic effect. Labetalol caused no consistent change in the release of ET-1 in HUVECs. Oral labetalol treatment did not affect urinary excretion of PGI, and TxA., metabolites.Conclusions: No clinically relevant effects of labetalol were found on endothelial cell PG1-, or ET-1 production. Labetalol at therapeutic doses and concentrations does not affect the production of vasoactive PGI2 and TxA2 in preeclamptic patients.

We compared the tocolytic effect of indomethacin and nylidrin in a prospective double-blind trial in which the appearance of the tocolytic treatment (always intravenous infusion and rectal suppositoriesoral capsules) was identical to the subjects. Sixty healthy women in imminent preterm labor between 25-34 weeks of singleton gestation were included. Thirty of these women received indomethacin (concomitantly with placebo infusion), with doses as follows day 1, 100-mg rectal suppository followed by two oral capsules (50 mg) at 8-hour intervals; days 2 and 3, three 50-mg oral capsules each day. Thirty women received intravenous nylidrin (concomitantly with rectaloral placebo), initiated with the dose of 50 µgminute and continued at the dose of 100-150 µgminute for a maximum of 3 days. Preterm labor was arrested for 24, 48, and 72 hours in 100, 96, and 90, respectively, of subjects in the indomethacin group, compared with 100, 76, and 73 of women in the nylidrin group; the difference was significant (P<.05) at 48 hours. Women progressed beyond 37 gestational weeks more commonly (P<.05) with indomethacin (21 of 30, 70) than with nylidrin (13 of 30, 43). Indomethacin treatment was accompanied by maternal side effects 20 of the time, significantly less commonly (P<.001) than with nylidrin (83). The neonatal outcome was similar in the two study groups. We conclude from this double-dummy technique trial that indomethacin is more effective and better tolerated than nylidrin in arresting imminent preterm labor.

Aggressive surgery may improve the outcome of patients with ovarian cancer. To assess the risk of operative complications, we analyzed 472 primary and 299 repeat operations for ovarian cancer in 536 women between 14-91 years of age. Intraoperative bleeding estimated to be over 1000 mL (N107) was more common after primary (21) than repeat surgery (3). Urinary tract infection accompanied 113 operations (18 of primary and 9 of repeat), bowel complication 51 operations (7 of primary and 6 of repeat), fever 23 operations (4 of primary and 1 of repeat), wound complication 17 operations (3 of primary and 1 of repeat), and thromboembolism 11 operations (2 of primary and 0.3 of repeat). Patient age had no effect on the rate of complications. Pelvic and para-aortic lymphadenectomy in connection with primary operations caused substantial blood loss. Five subjects (1) died after primary operations. On the whole, the surgical procedures, especially repeat operations, were well tolerated and should not be avoided for fear of complications.

Background. Many questions have been raised recently about the relationship between infertility, fertility drugs and cancer. This prompted us to evaluate our patients having ovarian or breast cancer with a known history of infertility.Methods. We report thirteen women who had been examined and/or treated for infertility before the occurrence of malignant tumors of the ovary or the breast at an age under 50 years in 1990-1995 in our unit.Results. Mean age of the patients was 35 years (s.d. 5.9 years, range 28-47 years). Of the 11 ovarian tumors, one was a malignant teratoma, two were granulosa cell tumors and eight epithelial ovarian cancers. Ten women had received either clomiphene citrate alone or together with gonadotrophins, one had used only gonadotrophins, and in two patients ovarian cancer was detected during an infertility work-up but before any treatment. Four women had used clomiphene for more than twelve cycles. Two patients had ductal breast cancer. Conclusions. Our patients emphasize the need for follow-up and long-term prospective studies in infertile women who have been evaluated or treated for infertility.

To compare the abortifacient efficacies of two intravaginally administered misoprostol doses and gemeprost in termination of second-trimester pregnancy.

The etiology of primary dysmenorrhea, which is the most common gynecologic complaint and cause of lost working hours, remains obscure but merits careful scientific investigation. Recent studies suggest that increased endometrial prostaglandin production and release may be responsible for dysmenorrhea. Prostaglandins cause myometrial contractility that, if excessive, leads to uterine ischemia and pain. This hypothesis has led to clinical trials of antiprostaglandin agents such as indomethacin and fenamates, which inhibit the synthesis of prostaglandin through the prostaglandin synthetase system as well as antagonize their action at the cell receptor level. The good response of dysmenorrhea to other conventional forms of therapy such as oral contraceptives and dilatation of the cervix can be partly explained on the basis of a reduced level of prostaglandins in the menstrual fluid with such therapy. There is a definite need for further evaluation of the antiprostaglandin compounds in the treatment of dysmenorrhea so that sound formulations can be evolved for the elimination of this incapacitating disorder.

Objective: To compare the long-term effects of oral and transdermal hormone replacement therapy (HRT) on carotid and uterine vascular impedance.

During 1969-1974 six hundred and forty-nine external versions were attempted during the last trimester on 491 mothers with fetal malpresentation. the procedure was monitored with ultrasound in 1969-1974. Most of attempts (70.0%) were made during the 32nd-36th weeks. the final version rate after one or more attempt was 76.2%, being lower (67.0%) in nulliparous than parous women (84.6%). the incidence of breech presentation at birth decreased from 4.5 to 2.9% (p<0.001). the most serious complication was one premature labor but the infant survived. the perinatal mortality was 2.0% and, after excluding abnormal infants, 0.8%. the combination of external version and the use of ultrasound is a safe method which avoids hazardous vaginal breech delivery and is recommended in obstetric practice.

In order to assess anterior pituitary function during the puerperium, 20 women were studied by 14 intravenous LRH and 10 TRH stimulation tests within 2-10 days post-partum. The basal FSH level (150-340 ng/ml) was within the normal non-pregnant range for the follicular phase of the menstrual cycle (50-350 ng/ml) and did not increase after 100 μg of synthetic LRH. The TSH (3.3-8.8 μU/ml) was high and increased after 200 μg of synthetic TRH about twofold. Obstetrical parameters (e.g. milk excretion, pregnancy complication, type of delivery or the amount of bleeding during delivery) were not associated with significant changes in FSH or TSH levels or in the responses to TRH stimulation.