Early outcome of myomectomy by laparotomy, minilaparotomy and laparoscopically assisted minilaparotomy. A randomized prospective study

BACKGROUND: To compare in the first 7 days after surgery the outcome of myomectomy performed by three laparotomic approaches: laparotomy (LT), minilaparotomy (MLT) and laparoscopically assisted minilaparotomy (LA-MLT). METHODS: Fifty-one women with 5-15 cm total myoma diameter were randomized blindly using a computer randomization list, to LT (n = 17), MLT (n = 17) or LA-MLT (n = 17). RESULTS: Mean operation length was similar in the three groups. Mean (+/- SEM) time of paralytic ileus (55.0 +/- 4.5 versus 33.4 +/- 3.4 h; P < 0.01) and discharge (141.6 +/- 5.2 versus 81.5 +/- 8.2 h; P < 0.01) was longer in LT than LA-MLT or even MLT. In comparison with LA-MLT, LT induced a greater haemoglobin decline (-3.07 +/- 0.3 versus -1.8 +/- 0.15 mg/dl; P < 0.025), and a greater post-operative stress, as documented by increased prolactin (+15.1 +/- 3.8 versus +0.16 +/- 4.5 ng/ml; P < 0.03) and decreased insulin sensitivity (fasting glucose/insulin; -7.5 +/- 2.6 versus -0.7 +/- 2.1; P < 0.02). Seven days after surgery, abdominal pain (P < 0.05) was higher after LT (3.0 +/- 0.6) than MLT (0.5 +/- 0.2) and LA-MLT (0.9 +/- 0.4). CONCLUSIONS: In selected cases, myomectomy by LA-MLT offers some advantages versus LT and, to a smaller extent, MLT.     

Endothelin-1 and nitric oxide levels are related to cardiovascular risk factors but are not modified by estradiol replacement in healthy postmenopausal women. A cross-sectional and a randomized cross-over study

OBJECTIVE: To evaluate whether in healthy postmenopausal women endothelial substances such as endothelin-1 (ET-1) and nitric oxide are related to cardiovascular risk factors and can be influenced by estradiol replacement. DESIGN: A cross-sectional evaluation and a randomized, double-blind, placebo-controlled study with cross-over. METHODS: In 20 healthy postmenopausal women it was investigated the relation of ET-1 and NOx with age, BMI, 24-h blood pressure, lipid and glucose metabolism, and coagulation parameters. In addition, in the same women, the role played by estrogens on circulating ET-1 and stable derivatives of nitric oxide (nitrite/nitrates) was investigated by administering for 2 months transdermal estradiol (50 microg/day) vs. placebo. RESULTS: ET-1 and NOx were inversely related to each other (r=0.458; P=0.016). Multivariate analysis of regression showed that ET-1 levels were related directly to LDL-cholesterol (r=0.585; P=0.0005) and protein C (r=0.516; P=0.0008), and inversely to insulin (r=0.488; P=0.0065). The ratio NOx/ET-1 was directly related to HDL-cholesterol (r=0.441; P=0.005). The above relations were not influenced by estradiol. Indeed, in comparison to placebo, transdermal estradiol, besides reducing nocturnal systolic (P=0.002) and diastolic (P=0.03) blood pressure, did not modify ET-1 or NOx levels, as well as, any of the parameters considered. CONCLUSIONS: The relation of several cardiovascular risk factors with ET-1 and NOx/ET-1 suggests a primary role for these endothelial products in the determination of the cardiovascular risk of women. The present data do not support a role for transdermal estradiol in modifying ET-1 or NOx levels of healthy postmenopausal women.     

Hormonal contraception: venous and arterial disease

Objectives: The aim of this review was to evaluate whether the biological and epidemiological evidence is concordant in suggesting that levonorgestrel (LNG)-based hormonal contraceptives (HCs) are safer than newer formulations with regard to their effect on the cardiovascular system.

Methods: A narrative review was carried out of the modification of risk factors for venous thromboembolism (VTE) and arterial diseases induced by different HCs. Limits and concordance with epidemiological data were addressed.

Results: The data indicate general concordance between modifications of risk factors and epidemiology of VTE, with LNG-based HCs showing lower risk compared with most new formulations. Evidence for drospirenone (DRSP)-containing HCs is conflicting. LNG-based HCs are less favourable than HCs containing non-androgenic progestins, particularly DRSP, on risk factors for arterial events. Epidemiological studies do not consistently show a difference in arterial disease outcomes between different HCs; however, by evaluating women up to the age of 50, they do not take into consideration the time lag necessary for atherosclerosis to develop.

Conclusions: As a consequence of the different risk factors involved, and the different time lags between HC use and the manifestation of VTE or arterial diseases, the available epidemiological data do not give a reliable estimate of the cardiovascular risk associated with the use of different HCs. LNG-based HCs are safer than newer HCs as regards VTE risk, but biological data indicate that they are less favourable, particularly than HCs containing DRSP, on risk factors for atherosclerosis. Because of the limits of actual epidemiological evidence regarding arterial disease, modifications of arterial risk factors should be taken into consideration when considering individual long-term safety of HC use.     

Impact of transvaginal hydrolaparoscopy ovarian drilling on ovarian stromal blood flow and ovarian volume in clomiphene citrate-resistant PCOS patients: a case-control study

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in gynecology. In PCOS patients vascularization parameters are altered. Transvaginal hydrolaparoscopy (THL) is a mini-invasive approach for ovarian drilling in PCOS patients. In this study, we assessed the effect of ovarian drilling using THL on ovarian volume (OV) and vascularization index (VI) using 3D power Doppler ultrasonography in CC-resistant PCOS patients. A case-control study on 123?CC-resistant PCOS women who underwent THL ovarian drilling was performed. Patients underwent 3D ultrasound and power Doppler to measure VI, flow index (FI), vascularization flow index (VFI) and to evaluate OV before and after the procedure, at six months, and on the early follicular phase of the menstrual cycle. After THL ovarian drilling, OV and power Doppler flow indices were significantly reduced compared to pre-operative values (OV: 7.85 versus 11.72?cm³, p?p?p?p?相似文献   

Continuous combined hormone replacement therapy with oral 17beta-estradiol and norethisterone acetate improves homocysteine metabolism in postmenopausal women.

OBJECTIVE: To evaluate the effect of a continuous combined oral hormone replacement therapy (HRT) on basal and post-methionine load homocysteine levels in postmenopausal women. DESIGN: Twenty-two postmenopausal women (PMW) were randomly allocated to receive either continuous combined oral HRT (2 mg of estradiol plus 1 mg of norethisterone acetate; n = 11) or no treatment (controls, n = 11) for 6 months. A methionine oral load (0.1 g/kg body weight) was performed in each subject at time 0 and after 6 months. Serum homocysteine levels were measured by high-performance liquid chromatography in samples collected at time 0 and at 4, 8, and 24 h after the methionine load, while levels of vitamin B6 (by high-performance liquid chromatography) and B12 and folate (both by ELISA) were assayed in samples collected at time 0. RESULTS: Serum levels of glucose and body mass index increased in treated PMW, whereas folate decreased in controls. In treated PMW, basal homocysteine tended to decrease (10.6 +/- 3.3 micromol/L vs. 9.62 +/- 2.8 micromol/L, p = 0.062), whereas in controls it significantly increased (10.7 +/- 2.65 micromol/L vs. 12.17 +/- 3.89 micromol/L, p < 0.05). This increase was not significant after correction for vitamin status (p = 0.072). Homocysteine values 4 h (31.9 +/- 13.53 micromol/L vs. 39.83 +/- 22.53 micromol/L, p < 0.05) and 8 h (35.1 +/- 13.13 vs. 43.34 +/- 22.15 micromol/L) after methionine, and integrated homocysteine response to methionine (392.5 +/- 133.8 micromol/24 h vs. 458.8 +/- 104.8 micromol/24 h; p < 0.05), were significantly reduced in HRT-treated, but not in untreated, PMW. CONCLUSIONS: Continuous combined oral HRT with17beta-estradiol plus norethisterone acetate reduces homocysteine levels, mainly after a methionine load. This effect seems to be independent of vitamin status and may have positive implications for the prevention of cardiovascular diseases in PMW.     

Different circulatory response to melatonin in postmenopausal women without and with hormone replacement therapy

In young men and women, melatonin influences vascular reactivity and reduces blood pressure and norepinephrine levels. Herein, we investigated whether these effects are conserved in postmenopausal women without and with hormone replacement therapy (HRT). Oral melatonin (1 mg) or placebo was randomly and in double blind fashion administered to 18 untreated and 13 postmenopausal women who were treated continuously with transdermal estradiol (50 microg/day) plus cyclic medroxyprogesterone acetate (5 mg/day x 12 days every 28 days). Internal carotid artery pulsatility index (PI), an index of downstream resistance to blood flow, blood pressure and catecholamine levels were evaluated. In untreated postmenopausal women, melatonin was ineffective, while in HRT-treated women, studied during the only estrogenic phase, melatonin reduced, within 90 min, systolic (-8.1 +/- 9.9 mmHg; P = 0.054), diastolic (-5.0 +/- 7.0 mmHg; P = 0.049) and mean (- 6.0 +/- 6.6 mmHg; P = 0.037) blood pressure. Norepinephrine (-50.1 +/- 66.7 pg/mL; P = 0.019), but not epinephrine levels, were also significantly reduced. Similarly, resistance to blood flow in the internal carotid artery, as evaluated by the PI, decreased (-0.190 +/- 0.15; P = 0.0006) in a way that was linearly related to pre-existing PI values (r2 = 0.5; P = 0.0059). These data show that the circulatory response to melatonin is conserved in postmenopausal women on HRT but not in untreated postmenopausal women. Possible physiological and pharmacological implications of these data on the cardiovascular risk of postmenopausal women can be envisioned.     

Amplification of pulsatile LH secretion by exogenous melatonin in women

The effect of melatonin on pulsatile LH secretion was investigated in early follicular phase women (days 2-5). During two consecutive days, at 0800 hrs., subjects received placebo or oral melatonin in a random double-blind fashion. Two doses of melatonin were used; 100 mg single dose (N = 6) or 2.5 mg in three divided doses (N = 5), (1 mg at 0800 hrs., 0.75 mg at 1000 and 1200 hrs.). Blood samples were collected every 10 minutes, between 0900-1700 hrs. Compared with placebo, melatonin administration augmented LH pulse amplitude (p less than 0.01) without changing LH pulse frequency. The integrated LH secretion was significantly increased (p less than 0.01) after melatonin, independent of doses administered. Serum FSH and ovarian steroids were not altered. It is concluded that exogenous melatonin enhances LH pulse amplitude in women, without modifying FSH and ovarian steroid levels.     

Melatonin: a major regulator of the circadian rhythm of core temperature in humans.

The circadian rhythm of core body temperature (BTc), with maxima during the day and minima at night, is normally coupled with the sleep-wake cycle. Pineal melatonin secretion occurs contemporaneously during the nighttime hours and is mediated by the activation of beta-adrenergic receptors during darkness. The hypothesis that nocturnal melatonin secretion may be involved in the regulation of the human circadian BTc rhythm was examined. The temporal relationship between melatonin and the circadian BTc rhythm was characterized in 12 young women, normally entrained to the light-dark cycle. Melatonin levels were manipulated through the administration of exogenous melatonin (2.5 mg, orally) during the daytime (n = 6) or suppression of endogenous nocturnal melatonin secretion by the beta-adrenergic antagonist atenolol (100 mg; n = 6) in double blind placebo-controlled experiments conducted during 2 consecutive days. Serum melatonin levels and BTc were monitored at 20- and 10-min intervals, respectively. In a nightshift worker the temporal relationship between the circadian rhythm of melatonin and BTc was investigated before and after entrainment to a reversed wake-sleep cycle. Our data show that in normally entrained subjects, the time course and amplitude of nocturnal melatonin secretion were temporally coupled with the decline of BTc (r = 0.97; P less than 0.00001). The same occurred in the nightshift worker, both during the dissociation and after entrainment to the reversed sleep-wake cycle. Compared with placebo, administration of melatonin significantly reduced daytime BTc (P less than 0.01), and the suppression of melatonin (by atenolol) attenuated the nocturnal decline of BTc (P less than 0.01). Cosinor analysis showed that the amplitude of the circadian BTc rhythm was reduced by about 40% in response to both daytime melatonin administration (P less than 0.05) and nocturnal melatonin suppression (P less than 0.02). In conclusion, circadian rhythms of melatonin and BTc are inversely coupled. The demonstrated hypothermic properties of melatonin are accountable for the generation of at least 40% of the amplitude of the circadian BTc rhythm. Manipulation of melatonin levels might be clinically useful to resynchronize the BTc rhythm under conditions of BTc rhythm desynchronization.     

Acute modifications in the levels of daytime melatonin do not influence leptin in postmenopausal women

Melatonin shows a clear circadian rhythm with peak values at night, and may act directly with fat cells. Leptin, the anorexic hormone synthesized mainly by adipocytes, is produced in a circadian fashion, similar to that of melatonin. Accordingly, in the present study, we investigated whether melatonin may contribute to the rise in circulating leptin. The study was performed in postmenopausal women with 2 months of treatment with placebo or estradiol (50 microg/day). Melatonin was administered in doses of 1 mg by mouth versus placebo. In experiment 1, melatonin was administered at 08:30 hr. In experiment 2, at 08:30 hr and 10:30 hr, and in experiment 3 at 15:30 hr. Three blood samples, one every 15 min, were collected prior to the administration of melatonin and 2 hr after the administration of the single melatonin dose or the second melatonin administration (experiment 2). Following its administration, circulating melatonin reached pharmacological levels. In the three experiments, levels of leptin were not modified by the daytime administration of melatonin. These data indicate that, at least in daytime hours, acute modifications in daytime melatonin levels do not influence levels of leptin of postmenopausal women either without or with estradiol replacement. Accordingly, the metabolic, endocrine, reproductive and biological modifications induced by acute daytime melatonin in women do not seem to be mediated by modifications in circulating leptin.     

Course of primary headaches during hormone replacement therapy

OBJECTIVE: The aim of the present study was to evaluate how hormone replacement therapy (HRT) could influence the course of primary headaches in postmenopausal women. METHODS: Fifty patients presenting for clinical evaluation of menopausal status and suffering from headache were enrolled. The observational period lasted 7 months during which women filled in a diary with the clinical characteristics of headache attacks (frequency, days with headache, severity) and the analgesic use (no. of analgesic/month). Climacteric symptoms and both anxiety and depression were also measured. At the first visit the patients were divided into two groups: those suffering from migraine without aura (MwA) and those suffering from episodic tension-type headache (ETTH) and separately randomized. After a month of run-in period, they received two different HRT regimen, either: (1) transdermal estradiol 50 mcg every 7 days for 28 days plus medroxyprogesterone acetate (MAP) 10 mg/day from 15th to 28th day, or (2) oral conjugated estrogens 0.625 mg/day for 28 days plus MAP 10 mg/day for the last 14 days. Follow up evaluations were planned after 1, 3 and 6 months of treatment. RESULTS: While we did not observe any significance change regarding headache parameters in ETTH patients during both transdermal and oral treatment, the course of migraine was significantly affected by the route of HRT. Both frequency of attacks (F = 8.5; P < 0.000) and days with headache (F = 6.9; P < 0.000) significantly increased during HRT in the subgroup assuming oral formulation. On the contrary, no changes in the same parameters were found in the group taking transdermal treatment. Moreover, while severity of migraine was unaffected by HRT, analgesic consumption was significantly increased in the subgroup on oral treatment (F = 6.3; P = 0.001). CONCLUSIONS: HRT significantly affects the course of headache in postmenopausal migraine sufferers. Indeed, while the clinical pattern of ETTH remained stable throughout the observational period, patients suffering from MwA worsened their symptoms within the first 3 months of treatment. In particular, the oral route of administration significantly worsened migraine in comparison to the transdermal route.