Edmund Chada Baracat

Benefits of soy isoflavone therapeutic regimen on menopausal symptoms

OBJECTIVE To examine the change in menopausal symptoms and cardiovascular risk factors in response to 4 months of daily 100‐mg soy isoflavone in postmenopausal women. METHODS In this double‐blind, placebo‐controlled study, 80 women were randomly assigned to isoflavone (n = 40) and placebo (n = 40) treatment. The menopausal Kupperman index was used to assess change in menopausal symptoms at baseline and after 4 months of treatment. Cardiovascular risk factors were assessed by evaluating plasma lipid levels, body mass index, blood pressure, and glucose levels in the participants. To examine the effects of this regime on endogenous hormone levels, follicle‐stimulating hormone (FSH), luteinizing hormone (LH), and 17β‐estradiol were measured. Transvaginal sonography was performed to quantify endometrial thickness. RESULTS The data showed a decrease in menopausal symptoms (P < .01, paired t test, two‐tailed, between baseline and isoflavone groups, and P < .01, unpaired t test, between placebo and isoflavone groups). Total cholesterol and low‐density lipoprotein decreased significantly in the isoflavone group compared with the baseline or placebo group (P < .001, paired t test, two‐tailed, between baseline and isoflavone groups, and P < .01, unpaired t test, between placebo and isoflavone groups). The isoflavone treatment appeared to have no effect on blood pressure, plasma glucose, and high‐density lipoprotein and triglyceride levels. CONCLUSION This study suggests that isoflavone 100‐mg regime treatment may be a safe and effective alternative therapy for menopausal symptoms and may offer a benefit to the cardiovascular system.

Effects of hormone therapy with estrogen and/or progesterone on sleep pattern in postmenopausal women

To investigate the effects of estrogen and progesterone on sleep in postmenopausal women.

Assessment of the proliferative, apoptotic and cellular renovation indices of the human mammary epithelium during the follicular and luteal phases of the menstrual cycle

IntroductionDuring the menstrual cycle, the mammary gland goes through sequential waves of proliferation and apoptosis. In mammary epithelial cells, hormonal and non-hormonal factors regulate apoptosis. To determine the cyclical effects of gonadal steroids on breast homeostasis, we evaluated the apoptotic index (AI) determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining in human mammary epithelial cells during the spontaneous menstrual cycle and correlated it with cellular proliferation as determined by the expression of Ki-67 during the same period.MethodsNormal breast tissue samples were obtained from 42 randomly selected patients in the proliferative (n = 21) and luteal (n = 21) phases. Menstrual cycle phase characterization was based on the date of the last and subsequent menses, and on progesterone serum levels obtained at the time of biopsy.ResultsThe proliferation index (PI), defined as the number of Ki-67-positive nuclei per 1,000 epithelial cells, was significantly larger in the luteal phase (30.46) than in the follicular phase (13.45; P = 0.0033). The AI was defined as the number of TUNEL-positive cells per 1,000 epithelial cells. The average AI values in both phases of the menstrual cycle were not statistically significant (P = 0.21). However, the cell renewal index (CRI = PI/AI) was significantly higher in the luteal phase (P = 0.033). A significant cyclical variation of PI, AI and CRI was observed. PI and AI peaks occurred on about the 24th day of the menstrual cycle, whereas the CRI reached higher values on the 28th day.ConclusionsWe conclude that proliferative activity is dependent mainly on hormonal fluctuations, whereas apoptotic activity is probably regulated by hormonal and non-hormonal factors.

Sleep disturbances, oxidative stress and cardiovascular risk parameters in postmenopausal women complaining of insomnia

Objective The aim of this work was to investigate cardiovascular risk factors and oxidative stress parameters as well as sleep disturbances in polysomnography recordings of 38 postmenopausal women with insomnia. Methods Polysomnography recordings were performed on subjects for sleep analysis. Oxidative stress parameters were analyzed by measuring blood concentration of catalase, superoxide dismutase (SOD), thiobarbituric acid reactive substances (TBARS) and glutathione. For cardiovascular risk factors, we measured plasma levels of homocysteine, folic acid and vitamin B6. Results Findings of polysomnography recordings revealed: 68% experienced decreased sleep efficiency, 50% had apnea, 7.8% had periodic leg movements and 2.6% had bruxism (involuntary gnashing and grinding of the teeth during sleep). Our results showed that the majority of our subjects presented normal concentrations of the parameters studied according to standards reached in our laboratory. The only notable exception was TBARS. In this case, only 21% displayed normal values. We also found inverse correlations between SOD activity and both age and time of menopause. Conclusions Although all women complained of insomnia, 50% of them demonstrated apnea during polysomnography recordings. Of the parameters measuring oxidative stress, only TBARS levels were increased in our sample. Some clinical data, such as time of onset of menopause, may be associated with the oxidative stress status of these women, probably due to the lack of estrogen and to sleep disturbances, such as apnea.

Effects of pinealectomy and the treatment with melatonin on the temporal lobe epilepsy in rats

The aim of the present work was to analyze the effects of pinealectomy in the development of the epilepsy model induced by pilocarpine in adult male rats. Group I: Wistar male adult rats were submitted to pinealectomy, and 7 days after surgery, these animals received pilocarpine (350 mg/kg, i.p.) to induce three distinct behavioral phases: status epilepticus, seizure-free, and chronic phases. This late, as well as all control groups were continuously video-recorded for 60 days, to study behavior parameters. These animals were killed and the brain sections were processed for Nissl and neo-Timm. Group II: Another group, also submitted to pinealectomy, received several injections of melatonin (2.5 mg/kg): 20 min before, concomitantly with pilocarpine, 30 min, 1 h, and 2 h after pilocarpine administration. Some animals from group I and all from group II were sacrificed 48 h following status epilepticus onset to perform TUNEL assay. The latency for status epilepticus onset, status epilepticus length as well as mortality rate during status epilepticus were similar for pinealectomized and control groups. On the other hand, pinealectomized rats presented minor duration of the silent period, a higher number of spontaneous seizures during the chronic phase, increased number of TUNEL-positive cells (acute phase), increased neuronal loss, and marked supragranullar mossy fibers sprouting (chronic phase) in the hippocampal formation, when compared with control groups. Our data show that the pinealectomy facilitates the epileptogenic process that follows the long-lasting status epilepticus. This facilitation can be partially reverted by the simultaneous administration of melatonin.

Sleep in post-menopausal women: Differences between early and late post-menopause

OBJECTIVE The aim of this study was to evaluate the differences in sleep between women of early and late post-menopause. STUDY DESIGN Thirty post-menopausal women who came to the climacteric service of their own volition were selected. Fourteen were in early post-menopause (less than 5 years after menopause), and sixteen were in late post-menopause (more than 5 years since menopause). None of the women were suffering from any other clinical diseases. Participants had no previous history of hormone therapy or hypnotic drug use. These patients were not previously selected with regard to any sleep complaints. All participants answered a sleep questionnaire and underwent a polysomnography recording. RESULTS Subjective complaints included body pain, bruxism, anxiety, depression, lack of concentration, and sleepiness (measured by the Epworth Sleepiness Scale). These complaints were more frequent in the late post-menopause group. In contrast, complaints of memory impairment were more frequent in the early post-menopause group (p<or=0.05). Polysomnographic findings revealed no differences between the early and late post-menopause groups. CONCLUSIONS Although early menopause is associated with several symptoms, complaints related to sleep were higher in the late post-menopausal group.

Estrogen, progestogen and tamoxifen increase synaptic density of the hippocampus of ovariectomized rats

The effects of gonadal steroids or tamoxifen over the synaptic density of the CA1 region of the hippocampus was investigated in ovariectomized (OVX) rats. Chronic oral administration of conjugated equine estrogen, conjugated equine medroxyprogesterone, a combination of both or tamoxifen was performed in ovariectomized (OVX) rats over a period of 60 days. Synaptic density of the stratum radiatum of the CA1 region was evaluated by means of electron microscopy. Significant increases in the range of 34-49% were found for treated animals as compared to OVX controls not subject to hormonal replacement. Our results confirm previously reported effects of estradiol over synaptic density in this region and reports for the first time an effect of medroxyprogesterone (alone or in combination with estrogen) and tamoxifen. Our findings support the notion that hormonal replacement therapy and tamoxifen might have beneficial effects for cognitive function.

Effects of melatonin on the ovarian response to pinealectomy or continuous light in female rats: similarity with polycystic ovary syndrome.

The current study was conducted to investigate the relationship between melatonin and chronic anovulation. Adult (3-4 months old) female Wistar rats were submitted to pinealectomy: group I: pinealectomized ovariectomized melatonin-treated (N = 10); group II: pinealectomized ovariectomized placebo-treated (N = 12); group III: pinealectomized light-treated placebo-treated (N = 10) or maintained under continuous light; group IV: maintained under continuous light, ovariectomized melatonin-treated (N = 22); group V: maintained under continuous light, ovariectomized placebo-treated (N = 10); group VI: maintained under continuous light placebo-treated (N = 10). In order to assess ovarian modifications, unilateral ovariectomy was performed during the fourth month in groups I, II, IV, V and the other ovary was removed after 8 months. Ovariectomy was performed in groups III and VI only after eight months. Melatonin (200 micro g/100 g body weight) dissolved in 0.02 ml absolute ethanol was injected intramuscularly daily during the last 4 months into groups I and IV. The other groups were treated with placebo (NaCl). The ovarian cysts were analyzed and their area, perimeter and maximum diameter, as well as the thickness of the ovarian capsule were measured. Daily colpocytological smears were performed throughout the study. Persistent estrous condition and ovarian cysts were observed in all groups. In pinealectomized rats the ovarian and vaginal alterations disappeared at the end of the study and in rats maintained under continuous light the vaginal and ovarian polycystic aspect was reversed only in those treated with melatonin. We conclude that melatonin may act on the ovarian response reverting chronic anovulation induced by pinealectomy or continuous light.

Genetic polymorphisms of cytochrome P450c17α (CYP17) and progesterone receptor genes (PROGINS) in the assessment of endometriosis risk

We designed the present study in order to evaluate the eventual role of polymorphisms in the genes encoding cytochrome P450c17α (CYP17) and the progesterone receptor (PROGINS) as risk factors for endometriosis development. Eligible cases consisted of 121 women with surgically confirmed endometriosis who underwent treatment in a hospital in São Paulo, Brazil during the period from September 2003 to September 2005. The 281 controls were participants with normal gynecological as well as pelvic ultrasound evaluation, who did not have any gynecological conditions during their reproductive lives such as pelvic pain and/or dyspareunia nor infertility history. Genomic DNA was obtained from buccal cells and processed for DNA extraction using the GFX DNA extraction kit (GE Healthcare). The CYP17 (−34T→C) polymerase chain reaction–restriction fragment length polymorphism assay has been described previously, as has the progesterone receptor polymorphism (PROGINS) detection assay. PROGINS heterozygosis genotype frequencies were shown to be statistically higher in endometriosis cases compared with controls. On the other hand, differences in the CYP17 polymorphism (−34T → C) frequencies were not even close to significance (p = 0.278) according to our findings.

Glycosaminoglycan profile in bladder and urethra of castrated rats treated with estrogen, progestogen, and raloxifene

OBJECTIVE This study was undertaken to evaluate the action of conjugated equine estrogens alone, medroxyprogesterone, the combination of these estrogens with progestogens, and of raloxifene on the glycosaminoglycan profile in the bladder and urethra of adult oophorectomized rats in comparison with noncastrated rats. STUDY DESIGN Sixty adult rats, of which 50 were submitted to bilateral oophorectomy, were studied. After 4 days, the latter were assigned to five groups of 10 animals each. For 30 consecutive days the following treatments were given: group 1, conjugated equine estrogens; group 2, conjugated equine estrogens combined with medroxyprogesterone acetate; group 3, medroxyprogesterone; group 4, raloxifene; and group 5, placebo. Thereafter the bladders and urethras of the animals were removed, processed to yield a dry powder of which the sulfated glycosaminoglycan content was determined by densitometry after agarose gel electrophoresis and that of hyaluronic acid by a fluorimetric assay. RESULTS Glycosaminoglycans found in the bladder and urethra were dermatan sulfate, heparan sulfate, and hyaluronic acid. In the bladder, hypoestrogenism or replacement with estrogens led to a lower sulfated glycosaminoglycan content. Replacement with estrogens and/or medroxyprogesterone reverted this effect. Hypoestrogenism decreased the dermatan sulfate/heparan sulfate ratio and reduced hyaluronic acid content. Estrogen therapy reverted this alteration and medroxyprogesterone addition annulled the estrogenic effect. In the urethra, castration did not alter hyaluronic acid content and sulfated glycosaminoglycan content, but raloxifene decreased the latter. CONCLUSION Castrated rats had a decrease in sulfated glycosaminoglycans and hyaluronic acid content in the bladder. Hormonal replacement altered the quantity and quality of glycosaminoglycans. In the urethra, raloxifene reduced sulfated glycosaminoglycans.