The association of different progesterone preparations with preterm birth prevention.

Objective: We aimed to compare the efficacy of commonly available progesterone preparations for preterm birth prevention. Methods: A retrospective cohort study of all women treated with progesterone to prevent preterm birth and delivered in a single university-affiliated tertiary medical-center. Four progesterone preparations were compared: vaginal Endometrin 100 mg twice daily, vaginal Crinone 8% gel 90 mg daily, vaginal Utrogestan 200 mg daily, and intramuscular 17α-hydroxyprogesterone caproate (17-OHPC) 250 mg weekly. All women were considered at risk for preterm birth according to: prior preterm birth or cervical length below 25 mm measured during the second trimester. Significant maternal morbidity, pregnancy achieved by artificial reproductive technique and cerclage placement were excluded. Primary outcome was the rate of preterm birth prior to 37 weeks of gestation. Results: Overall, 422 women were allocated to four study groups according to progesterone preparation: Endometrin 175 (41.5%), Crinone 73 (17.3%), Utrogestan 154 (36.5%), and 17-OHPC 20 (4.7%). Rates of preterm birth prior to 37 gestational weeks were lowest on the Endometrin treatment group (12.6 versus 20.5, 17.5, and 35% in the rest, p = .05). Multivariate analysis revealed that the progesterone preparation was associated with preterm birth prior to 37 gestational weeks (LR = 8.3, p = .004). The need for maternal red blood cells transfusion was significantly higher in the Endometrin subgroup (4% versus 0 in all others, p = .018). This finding remained significant after adjustment to potential confounders (LR 16.44, p < .001). Neonatal outcomes did not differ between groups. Conclusions: Different progesterone preparations prescribed to women at risk, may possess different efficacy in preventing preterm delivery prior to 37 weeks of gestation.

The impact of obstetric gel on the second stage of labor and perineal integrity: a randomized controlled trial.

OBJECTIVE: Dianatal® is a bioadhesive gliding film which reduces the opposing force to vaginal childbirth. We aimed to investigate the safety, applicability, and impact of Dianatal® obstetric gel on second stage of labor and perineal integrity. METHODS: Low-risk singleton pregnancies at term were prospectively enrolled. Eligible women were randomly assigned to either labor management without using obstetric gel, or labor management using intermittent application of obstetric gel into the birth canal during vaginal examinations, starting at active phase of labor (≥4 cm dilation). The primary measured outcome was the length of second stage of labor. RESULTS: Overall, 200 cases were analyzed. Demographic, obstetrical, and labor characteristics were similar between the groups. Neither adverse events nor maternal or neonatal side effects were observed. The mean lengths of the active and second stages of labor were comparable between the obstetric gel-treated and the control groups (157 versus 219 min and 48 versus 56 min, respectively). None of the women had grade III/IV perineal tears. Maternal and neonatal outcomes were not negatively influenced by using obstetric gel. No difference was found after sub-group analysis for spontaneous vaginal delivery. CONCLUSION: Dianatal® obstetric gel is safe in terms of maternal or neonatal use. Albeit a trend toward shorter labor stages using Dianatal® obstetric gel, no significant differences were noted among the groups. In order to further investigate the influence of the obstetric gel on labor stage interval, perineal integrity and maternal and neonatal outcomes, larger randomized clinical trials are needed to be carried out.

Preliminary assessment of the therapeutic efficacy of continuous theta-burst magnetic stimulation (cTBS) in major depression: a double-blind sham-controlled study.

BACKGROUND: Theta-burst transcranial magnetic stimulation (TBS) has been shown to induce potent and long lasting effects on cortical excitability. In a previous open study, we demonstrated safety, tolerability and antidepressant properties of continuous TBS (cTBS) in major depression (MD). The present study was aimed to evaluate the therapeutic efficacy of cTBS in depressed patients using a double-blind, sham-controlled design. METHODS: Twenty nine patients with MD were randomized to receive either active cTBS to the right dorsolateral prefrontal cortex (n=15) or sham cTBS (n=14) for 10 consecutive work days. After the 10th session, patients who received sham TBS were crossed over to active cTBS which consisted of 10 daily sessions. Patients who received active cTBS continued with the same treatment protocol for additional 10 treatments. Each treatment session consisted of 3600 stimuli at an intensity of 100% of the active motor threshold. Severity of depression was assessed weekly. RESULTS: Overall, there was no significant difference in the degree of clinical improvement between active and sham cTBS groups. However, in patients whose medication status remained unchanged before the trial (n=8) and in those who were medication-free (n=3), active cTBS resulted in a significantly greater reduction of Hamilton depression scores as compared to sham cTBS. LIMITATIONS: A small sample size, confounding effect of medication and short treatment period. CONCLUSIONS: Our results suggest that the antidepressant effect of cTBS is modest, yet it might be beneficial to patients nonresponsive to ongoing pharmacological treatment. A direct comparison between cTBS and conventional rTMS protocols is warranted.

Motor cortex disinhibition in normal-pressure hydrocephalus.

OBJECT: Previous studies have shown a close association between frontal lobe dysfunction and gait disturbance in idiopathic normal-pressure hydrocephalus (iNPH). A possible mechanism linking these impairments could be a modulation of corticospinal excitability. The aim of this study was 2-fold: 1) to determine whether iNPH affects corticospinal excitability; and 2) to evaluate changes in corticospinal excitability following ventricular shunt placement in relation to clinical outcome. METHODS: Twenty-three patients with iNPH were examined using single- and paired-pulse transcranial magnetic stimulation of the leg motor area before and 1 month after ventricular shunt surgery. The parameters of corticospinal excitability assessed were the resting motor threshold (rMT), motor evoked potential/M-wave area ratio, central motor conduction time, intracortical facilitation, and short intracortical inhibition (SICI). The results were compared with those obtained in 8 age-matched, healthy volunteers, 19 younger healthy volunteers, and 9 age-matched patients with peripheral neuropathy. RESULTS: Significant reduction of the SICI associated with a decrease of the rMT was observed in patients with iNPH at baseline evaluation. Ventricular shunt placement resulted in significant enhancement of the SICI and increase of the rMT in patients who markedly improved, but not in those who failed to improve. CONCLUSIONS: This study demonstrates that iNPH affects corticospinal excitability, causing disinhibition of the motor cortex. Recovery of corticospinal excitability following ventricular shunt placement is correlated with clinical improvement. These findings support the view that reduced control of motor output, rather than impairment of central motor conduction, is responsible for gait disturbances in patients with iNPH.

Women gynecologists' attitude toward their own health.

BACKGROUND: Following the publication of the results of Women's Health Initiative in 2002 there have been gross changes in the attitude of women and physicians towards the risks and benefits of hormone replacement therapy (HRT). We evaluated the attitude of women gynecologist towards their own health, including adherence to recommended screening tests and self usage and prescription of hormone replacement therapy. MATERIAL/METHODS: Questionnaires regarding performance of screening tests, self usage and recommendation of HRT were posted by mail to all Israel's women gynecologists. RESULTS: Ninety questionnaires were eligible for analysis (43.2% response rate). Average age was 48+/-7.7 years. Only 7/90 (7.8%) gynecologists smoke regularly and average body mass index was 25+/-3.8 kg/m2. Most participants performed at least one screening tests in the past 2 years. The median interval from the last self breast exam, mammography, gynecologisy exam, Papanicolaou test, colonoscopy and bone density test was 0.2, 1.82, 1.79, 1.95, 3.27 and 1.41 years, respectively. Most of them (68.3%) did not routinely recommend HRT to their patients. The duration of self HRT usage ranged between 1-20 years (average 5.1+/-3.4 years). Most gynecologists (87.7%) recommended continuous estrogen and progesterone for women with their uterus in place. CONCLUSIONS: The health profile of Israeli women gynecologists is chracterized by a high performance of screening tests for cancer and low rate of smoking. Our study also demonstrates that the impact of the results of the WHI trial is still well manifested and most Israeli women gynecologists do not routinely recommend HRT to postmenopausal women.

Activation of GRP78 on endothelial cell membranes by an ADAM15-derived peptide induces angiogenesis.

Impaired angiogenesis is one of the features of ischemic diseases. We have previously identified, by screening a phage display peptide library, a peptide that induces angiogenesis in endothelial cells under hypoxic conditions by binding the cell's membrane heat shock protein GRP78. Protein data base search identified 4 amino acids (HWRR) of that synthetic peptide present on the ADAM15 metalloprotease domain, a protein considered to be involved in neovascularization. Three peptides were synthesized according to the ADAM15 sequence placing HWRR at different positions. Peptide ADoPep1 exhibited significant angiogenic properties under hypoxic conditions as determined by cell proliferation, migration and tube formation. In a mouse hind limb ischemia model, a single injection of the peptide restored blood perfusion. The identified peptide was found to activate GRP78 on endothelial cell membrane and siRNA directed against the GRP78 mRNA interfered with induction of angiogenesis by the peptide. The peptide binding induced a decrease in heat shock protein GRP78 that is overexpressed under hypoxic conditions. The mechanism of peptide-induced angiogenic activity involves inhibition of apoptosis as well as increased Akt phosphorylation and ERK 1/2 activation. The peptide did not induce VEGF receptor-2 protein synthesis and phosphorylation, suggesting a VEGF-independent mechanism of angiogenesis.

Safety, tolerability and preliminary evidence for antidepressant efficacy of theta-burst transcranial magnetic stimulation in patients with major depression.

The aim of this open study was to evaluate the safety and tolerability of theta-burst transcranial magnetic stimulation (TBS) and to assess preliminarily its therapeutic efficacy in patients with major depression. A total of 33 patients were assigned to receive one of four TBS protocols for 10 consecutive work days. TBS consisted of triple-pulse 50-Hz bursts given at a rate of 5 Hz to the left or right dorsolateral prefrontal cortex at different stimulation parameters. Severity of depression was assessed by the Hamilton Depression Rating Scale. Our results indicate that TBS as applied in this study is safe and well tolerated in depressed patients and seems to have antidepressant properties. Increase of stimulation parameters is not associated with more side-effects and adds to its therapeutic effect.

[The feminization of obstetrics and gynecology].

Contemporary data indicate female dominance of obstetrics and gynecology. The authors sought to look for the effects of this domination on the discipline and further understand the reasons for these effects as reflected from the relevant current literature. Data clearly show a worldwide "creeping" process of female domination in the field of obstetrics and gynecology. Gender bias is present in hiring policies both for residency and afterwards. Female physicians encounter specific gender problems such as pregnancy, maternity leave and the additional burden of taking care of their family. These tasks may interfere with academic medicine. Furthermore, personal characteristics of women, which favor them for patients, may affect their productivity within the framework of community medicine. None of the alleged problems, which were linked to female obstetrician-gynecologists, is irresolvable, assuming professional establishment, as well as government acceptance and proper planning.

Factors affecting the duration of the latency period in preterm premature rupture of membranes.

OBJECTIVE: To investigate the natural course of preterm premature rupture of membranes (PPROM) at <34 + 0 weeks and to identify factors that affect the duration of the latency period. DESIGN: A retrospective cohort study of all women diagnosed with PPROM prior to 34 + 0 weeks during 1998-2006. Latency period was defined as the time between onset of PPROM to either spontaneous delivery, labor induction at 34 + 0 weeks, or indicated delivery prior to 34 + 0 weeks because of suspected chorioamnionitis or nonreassuring fetal heart rate. RESULTS: The overall rate of PPROM was 1.4% (905/66,775), of which 46% (417/905) occurred at <34 + 0 weeks. Overall, the latency period exceeded 48 h in about 73.4% of cases (306/471). Women with short latency periods (<48 h) were characterised by higher degree of cervical dilatation and higher gestational age at admission and were more likely to be nulliparous. The duration of the latency period ranged between 0 and 59 days and was inversely related to gestational age at admission (r = -0.63, P < 0.001). Using Cox proportional hazards model, gestational age at admission (HR = 1.29, 95% CI = 1.22-1.37), oligohydroamnios (HR = 1.49, 95% CI = 1.18-1.87), cervical dilatation >1 cm (HR = 0.65, 95% CI = 0.52-0.83), fetal growth restriction (HR = 2.94, 95% CI = 1.24-6.94) and nulliparity (HR = 1.28, 95% CI = 1.12-1.63) were significantly associated with shorter duration of the latency period. CONCLUSION: In this study, we have identified several predictive factors for the duration of the latency period in cases of PPROM. This information may assist clinicians in risk stratification and in providing consultation for women presenting with PPROM prior to 34 weeks of gestation.

Intrapartum cervical lacerations: characteristics, risk factors, and effects on subsequent pregnancies.

OBJECTIVE: The purpose of this study was to assess the clinical characteristics, risk factors, and effects on subsequent pregnancies of intrapartum cervical lacerations. STUDY DESIGN: A retrospective study of all women who were diagnosed with clinically significant cervical lacerations from 1994-2006. Data were compared with a control group. The outcome of subsequent pregnancies for women in the study and control groups was analyzed. RESULTS: Of 81,047 deliveries, 131 (0.16%) were complicated by cervical lacerations. With multivariate logistic regression analysis, the cervical cerclage, precipitous labor, vacuum extraction, nulliparity, and use of episiotomy were associated independently with cervical lacerations. The outcomes of subsequent pregnancies for women in the cervical-laceration (n = 42) and control (n = 518) groups were similar. There were no cases of recurrent cervical lacerations. CONCLUSION: Careful inspection of the cervix should be considered in cases of precipitous labor, operative vaginal delivery, or cervical cerclage during pregnancy. Intrapartum cervical lacerations do not appear to affect the outcome of subsequent pregnancies.

Predictors of failed operative vaginal delivery: a single-center experience.

OBJECTIVE: The purpose of this study was to identify factors that predict operative vaginal delivery. STUDY DESIGN: A retrospective cohort study was conducted that included all women who underwent a trial of operative vaginal delivery between 1993 and 2006 at a major tertiary center. RESULTS: Operative vaginal delivery was attempted in 5120 of 83,351 deliveries (6.1%): 4299 vacuum extractions (84.0%) and 821 forceps deliveries (16.0%). Failures occurred in 8.6% of trials, more often with vacuum extraction (10.0% vs 1.3%; P < .001). Most vacuum extraction failures (72.6%) were followed by a trial of forceps delivery, which failed in 3.5% of cases. On multivariate logistic regression analysis, the use of forceps (vs vacuum; odds ratio [OR], 0.4; 95%CI, 0.2-0.7) and administration of analgesia (epidural: OR, 0.4 [95% CI, 0.2-0.7]; intravenous opiates: OR, 0.2 [95%CI, 0.1-0.6]) were associated with a lower risk of failure, persistent occiput posterior position (OR, 2.2; 95% CI, 1.4-3.5) and birthweight >4000 g (OR, 2.8; 95% CI, 1.6-4.9), with a higher risk. CONCLUSION: Fetal weight and head position should be evaluated carefully before operative vaginal delivery, and the use of analgesia should be encouraged.

Iron supplementation in pregnancy--does the preparation matter?

OBJECTIVE: To assess the use, side effects and discontinuation rates of iron preparations during pregnancy. DESIGN: Six hundred and twelve randomly selected postpartum women completed a questionnaire on iron supplement use in the second and third trimesters. RESULTS: Of the 517 women (84.5%) reported using iron supplements, 453 were eligible for the study. The most common preparation was ferrous fumarate (46.8%, P < 0.01), followed by ferrous sulfate (31.8%), ferric polymaltose (12.4%), and ferric bisglycinate (7.3%). Almost half the participants (45%) reported at least one adverse effect, especially constipation (27.4%, P < 0.01), nausea (10.8%). Multivitamin preparations and ferric bisglycinate were associated with the fewest side effects (23.7, 21.2% respectively, P < 0.01), and ferrous fumarate and immediate-release ferrous sulfate with the most (56.3, 53.7% respectively). Eighty-three women discontinued their originally prescribed iron preparation, mainly (89%) due to side effects. Discontinuation rates were lowest for the multivitamin and ferric bisglycinate (10.5, 9.1%, respectively). In most cases, the specific preparation was recommended by the women's physician (76%). CONCLUSION: Ferrous fumarate-containing multivitamin preparations and ferric bisglycinate, although infrequently recommended as the first-line of iron supplementation, may be associated with less side effects and better compliance.

Attitudes and knowledge on breastfeeding among paediatricians, family physicians, and gynaecologists in Israel.

OBJECTIVES: Many women in Western countries fail to breastfeed long enough. The aim of this study was to examine the attitudes and knowledge of Israeli family physicians (FPs), gynaecologists and paediatricians towards breastfeeding. DESIGN AND PARTICIPANTS: A questionnaire examined Physicians' attitudes towards breastfeeding and their role in encouraging it, their sources of information and adequacy of knowledge. RESULTS: Four hundred and seventy-eight physicians responded to the survey: 123 FPs, 134 gynaecologists and 221 paediatricians. Ninety to -hundred per cent of physicians agreed that breastfeeding is the best feeding method for infants and agree that physicians should encourage it. Less than 20% of physicians discuss breastfeeding with pregnant women, and less than 30% discuss it with women 3 months or more postnatally. On average, physicians correctly answered 3.5 +/- 1.7 out of seven questions examining knowledge. Physicians state their main sources of information as their own experience and reading. One hundred and ninety physicians specified how they encourage breastfeeding--of those, 75.3% speak only of the advantages of breastfeeding. CONCLUSION: Physicians have a positive disposition towards breastfeeding but their knowledge is somewhat low. It seems awareness is lacking to the importance of continuous support and practical guidance beginning before birth and continuing until 3 months or more postnatal.

Phyto-Female Complex for the relief of hot flushes, night sweats and quality of sleep: randomized, controlled, double-blind pilot study.

OBJECTIVE: To determine the efficacy and safety of the herbal formula Phyto-Female Complex (SupHerb, Netanya, Israel; ingredients: standardized extracts of black cohosh, dong quai, milk thistle, red clover, American ginseng, chaste-tree berry) for the relief of menopausal symptoms. METHODS: A randomized, double-blind, placebo-controlled trial in 50 healthy pre and postmenopausal women, aged 44-65 years, to whom oral Phyto-Female Complex or matched placebo was prescribed twice daily for 3 months. A structured questionnaire on the frequency and intensity of menopausal symptoms was administered weekly from one week before throughout the 3-month treatment period, followed by biochemical tests, breast check, and transvaginal ultrasonography. RESULTS: The women receiving Phyto-Female Complex reported a significantly superior mean reduction in menopausal symptoms than the placebo group. The effect of treatment improvements in menopausal symptoms increased over time; by 3 months there was a 73% decrease in hot flushes and a 69% reduction of night sweats, accompanied by a decrease in their intensity and a significant benefit in terms of sleep quality. Hot flushes ceased completely in 47% of women in the study group compared with only 19% in the placebo group. There were no changes in findings on vaginal ultrasonography or levels of relevant hormones (estradiol, follicle-stimulating hormone), liver enzymes or thyroid-stimulating hormone in either group. CONCLUSION: Phyto-Female Complex is safe and effective for the relief of hot flushes and sleep disturbances in pre- and postmenopausal women, at least for 3 months' use.

Levonorgestrel-releasing intrauterine system as an adjunct to estrogen for the treatment of menopausal symptoms--a review.

Exogenous estrogen is an effective means of prevention for postmenopausal symptoms. Estrogen treatment should be combined with progesterone in non-hysterectomized women to prevent estrogen-induced malignant transformation of the endometrium. Progesterone supplementation using continuous combined estrogen + progesterone treatment may result in an increased incidence of breast cancer and cardiovascular disease. In addition, progesterone supplementation with sequential estrogen + progesterone treatment may cause immediate adverse effects, such as irregular bleeding and spotting, breast congestion, fluid retention, abdominal distention, and a change in lipid profile. All these effects are related, at least in part, to the progesterone component of the therapy.To avoid these complications, researchers are seeking safer progestational components and different modes of administration. In this article we review the findings on the use of the novel levonorgestrel-releasing intrauterine system as a therapeutic tool for localized, rather than systemic, progesterone administration in postmenopausal women.

Angiogenesis induced by novel peptides selected from a phage display library by screening human vascular endothelial cells under different physiological conditions.

Angiogenesis is a process modulated by several endogenous vascular growth factors as well as by oxygen conditions. For example VEGF failed to induce useful therapeutic angiogenesis in clinical trials. We used a combinatory phage display peptide library screening on human umbilical endothelial cells under normoxia and hypoxia conditions in order to identify novel peptides that bind endothelial cells. The identified peptides induced angiogenesis as demonstrated by endothelial cell proliferation, migration and tube formation. Injection of peptides into the ears of mice resulted in increased numbers of blood vessels. Peptides did not induce VEGF receptor gene expression indicating a possible VEGF unrelated mechanism.

Granular cell tumor of the vulva: six new cases.

Granular cell tumors are rare neoplastic skin and soft tissue lesions: only 1-2% are malignant. Five to sixteen percent occur in the vulva. We present our experience with granular cell tumors of the vulva in six patients, all of whom had wide local excisions and were followed-up in our outpatient clinic for 3-171 months. One died of an unrelated cause. None of the others has evidence of the disease.

Use of various contraceptive methods and time of conception in a community-based population.

AIMS: To investigate the association between method of contraception and time to conception in a normal community-based population. DESIGN: Prospective, cross-sectional, survey. SETTING: Large comprehensive ambulatory women's health center. PATIENTS AND METHODS: One thousand pregnant women at their first prenatal obstetrics visit were asked to complete a self-report questionnaire. The return to fertility was analyzed by type of contraceptive method, duration of use, and other sociodemographic variables. RESULTS: Response rate was 80% (n=798). Mean age of the patients was 29.9+/-5 years. Seventy-five percent had used a contraceptive before trying to conceive: 80% oral contraceptives, 8% intrauterine device, and 7% barrier methods. Eighty-six percent conceived spontaneously. Contraceptive users had a significantly higher conception rate than nonusers in the first 3 months from their first attempt at pregnancy. Type of contraception was significantly correlated with time to conception. Pregnancy rates within 6 months of the first attempt was 60% for oral contraceptive users compared to 70 and 81% for the intrauterine device and barrier method groups, respectively. There was no correlation between time to conception and parity or duration of contraceptive use. Other factors found to be significantly related to time to conception were older age of both partners and higher body mass index. CONCLUSIONS: Contraception use before a planned pregnancy does not appear to affect ease of conception. Type of method used, although not duration of use, may influence the time required to conceive.

Mode of delivery in pregnant women with hypertensive disorders and unfavorable cervix following induction of labor with vaginal application of prostaglandin E.

BACKGROUND: Our aim was to evaluate the mode of delivery in pregnant women with hypertensive disorders and unfavorable cervix following induction of labor with vaginal application of prostaglandin E(2) (PGE(2)) near or at term, and to define the predictors of successful vaginal delivery in such women. METHODS: In a retrospective case-controlled study, pregnant women with hypertension, who underwent labor induction with PGE(2) tablets (study group, n = 284), were compared with women, who underwent elective induction of labor (group 2, n = 115), and women with normal spontaneous onset of labor (group 3, n = 510). RESULTS: The rate of cesarean section (CS) was significantly higher in the study group (25.3%) than in group 2 (14.8%) and in group 3 (9%). Exclusion of the nulliparous women from the study and control groups yielded similar CS rates in the study group (16.9%) and in group 2 (11.1%). Women with pre-eclampsia and the women with chronic hypertension or pregnancy-induced hypertension had similar rates of CS. In logistic regression model, nulliparity, induction of labor with PGE(2), and maternal age, but not hypertensive disorders, were independently and significantly associated with increased risk of CS. CONCLUSIONS: PGE(2) induction of labor is successful in approximately 75% of patients with hypertensive disorders and unfavorable cervix, with apparently no serious maternal or fetal complications. The induction of labor by itself, and not the hypertensive disorders in pregnancy, is independent risk factor for CS.

Effect of electroconvulsive therapy on cortical excitability in patients with major depression: a transcranial magnetic stimulation study.

OBJECTIVE: The antidepressant action of electro-convulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) may be related to their ability to modulate cortical excitability. The aim of this study was to investigate changes in cortical excitability following ECT in patients with major depression (MD) and to compare therapeutic efficacy of ECT combined with rTMS to that of ECT alone. METHODS: Twenty-two patients with MD were assigned to receive ECT and right prefrontal 1 Hz rTMS (n=12) or ECT with sham rTMS (n=10). ECT was given twice weekly and rTMS was applied on the remaining 4 days, throughout 3 weeks. The resting motor threshold (rMT) and motor evoked potential (MEP)/M-wave area ratio were evaluated before and 6 h after the first, third and sixth ECT session. The active motor threshold (aMT), intra-cortical inhibition (ICI) and intra-cortical facilitation (ICF) were measured at baseline and 24 h after the last ECT. RESULTS: There were no significant differences in the degree of clinical improvement and measures of cortical excitability in the ECT+active rTMS group as compared to the ECT+sham rTMS group. Marked clinical improvement observed in 19 out of the 22 patients was associated with a significant increase of the MEP/M-wave area ratio, decrease of the aMT and reduction of the ICI in the left hemisphere. CONCLUSIONS: The antidepressant effect of ECT was associated with an enhancement of left hemispheric excitability. rTMS did not add to the beneficial effect of ECT. However, the small sample size and the robust effect of ECT might have obscured a potential therapeutic effect of rTMS. SIGNIFICANCE: Measures of cortical excitability may provide insight to our understanding of the mechanism of action of ECT and might be useful for the assessment of treatment response.