Steroid Withdrawal Research Articles

State-of-the-art immunosuppression protocols for pediatric renal transplant recipients.

Immunosuppressive protocols used in pediatric kidney transplantation have changed substantially within the last decade. Many transplant centers now focus on the use of tacrolimus and mycophenolate mofetil in combination with early steroid withdrawal, frequently combined with antibody induction therapy. However, this approach is mainly based on treatment efficacy and-compared to other immunosuppressive regimens used in this context-leads to higher rates of viral infections in patients. In this review I assess data from prospective, interventional trials of immunosuppressive therapy in pediatric kidney transplantation. However, since there is a paucity of randomized controlled trials, I also describe the results of studies with weaker designs. The advantages and disadvantages of different immunosuppressive strategies are discussed. Within this framework I suggest ideas for individualized immunosuppressive regimens based on different stratificators that could effect a change from a 'one size fits all' to a tailored approach for initial and maintenance immunosuppressive therapy after renal transplantation in the pediatric setting.

Preoperative optimization of patients with inflammatory bowel disease undergoing gastrointestinal surgery: a systematic review.

Surgical management of inflammatory bowel disease (IBD) is a challenging task. The aim of preoperative optimization (PO) is to decrease the risk of complications and reduce the length of postoperative stay. The aim of this study was to review and grade the available evidence, attain clear recommendations, and point out potential future research. Studies were identified from electronic databases (PubMed, Embase, and Cochrane Library) and scanning reference lists in relevant papers. English-written studies examining PO in adult patients with IBD were included. Eight PO factors were investigated. Management of IBD is a multidisciplinary task. Steroid withdrawal is recommended while steroid stress dose is not recommended. Thiopurines appear to be safe, but it may be prudent to plan the procedure remotely from the last dose of an anti-TNF agent. Nutritional risk screening is recommended to unveil and correct any malnutrition. Thrombosis prophylaxis prior to surgery is well supported by evidence while extended 4-week prophylaxis needs further research. Percutaneous ultrasound or CT-guided drainage for intra-abdominal abscesses is recommended, but it is unclear for how long supplementary antibiotics (ABs) should be used. Oral AB 24h prior to open surgery might improve outcome if given as complementary to IV perioperative AB. Mechanical bowel preparation is not supported by evidence. Comorbidities must be treated accordingly prior to surgical intervention. Smoking cessation can be beneficial for wound healing. Multimodel PO intervention in IBD patients is recommended.

Successful therapy with mycophenolic acid in a membranous glomerulonephritis due to Kimura disease

Kimura disease (KD) is a rare inflammatory soft tissue disorder of unknown origin most frequent in Asians, the prevalence of which is growing in Western countries. Painless papules and/or nodules with a predilection for the head and the neck region, lymphadenopathies, parotid gland involvement, eosinophilia, and raised IgE levels are parts of its presentation. Renal involvement with various forms of glomerulonephritis, including membranous nephropathy (MN), can occur and is generally associated with a proteinuria that encompasses nephrotic syndrome. Corticosteroids are the mainstay of treatment of KD-associated glomerulonephritis, but steroids withdrawal is often followed by relapsing nephrotic syndrome. Various immunosuppressive agents have been tested to prolong the remission of KD-associated nephrotic syndrome while tapering steroids, but they are only partly effective or associated with significant complications. To the best of our knowledge, we describe here the first case of KD-related membranous glomerulonephritis with a favorable evolution and a sustained remission of 4years under prolonged therapy with mycophenolic acid (MPA). MPA and its active metabolite, mycophenolate mofetil (MMF), treatments as supportive therapies to corticosteroids and ACE inhibitors should be further investigated in KD-related membranous nephropathies. .

Effective and Safe Reduction of Conventional Immunosuppressants Using Everolimus in Maintenance Kidney Transplant Recipients

BackgroundAdverse events due to conventional immunosuppressive therapy decrease both graft and patient survival. We aimed to establish a new protocol using everolimus (EVR) to safely minimize conventional immunosuppressants in maintenance kidney transplant recipients. MethodsA total of 86 consecutive kidney transplant recipients with no complications were maintained with triple-drug combination therapy (conventional group). In case of complications, the administration of very low-dose tacrolimus (C0: 5.0 to <3.0 ng/mL), reduced mycophenolate mofetil (1000–1500 to 500–1000 mg), and EVR (C0: 3.0–5.0 ng/mL) and methylprednisolone withdrawal (2–4 to 0 mg) were simultaneously conducted (EVR group). Graft survival and acute rejection rate were compared between groups. Within the EVR group, the dose of conventional immunosuppressants was compared between pre- and post-EVR administration. Renal function was evaluated 1 year post-EVR administration. ResultsAll grafts survived in the conventional (n = 50) and EVR (n = 36) groups, and biopsy-proven acute rejection rate exhibited no significant difference between these groups (12% vs 17%; P = .55). Furthermore, no acute rejection occurred post-EVR administration. In the EVR group, all immunosuppressants significantly decreased post-EVR administration compared with those pre-EVR administration (P < .01), and serum creatinine significantly improved at postoperative year 1 (P = .031). ConclusionsEVR administration enables very low-dose tacrolimus administration, helps reduce mycophenolate mofetil and steroid withdrawal, and ameliorates renal function in maintenance kidney transplant recipients experiencing complications associated with conventional immunosuppressive therapy.

Systematic Review of the Topical Steroid Addiction and Topical Steroid Withdrawal Phenomenon in Children Diagnosed With Atopic Dermatitis and Treated With Topical Corticosteroids

ABSTRACT Background A 2015 National Eczema Association study concluded that topical steroid withdrawal is an effect of prolonged, frequent use of topical steroids occurring mostly in adult women. It is unclear whether children develop topical steroid withdrawal. Objective The aim of this study was to assess current evidence regarding topical steroid withdrawal in children. Methods This study is a systematic review of medical literature as well as online social media sites and blogs regarding topical steroid withdrawal in children. Results Literature search yielded zero studies on/or reporting classic topical steroid withdrawal in children; however, periorificial dermatitis, which is generally a steroid-induced disorder in children, was reported in &gt;320 cases. Of 142 social media blogs on topical steroid withdrawal, 26 were blogs discussing children. Twenty-seven cases were included in this review. Length of topical steroid use ranged from 2 months to 12 years. Conclusions Topical steroid withdrawal occurs in children and can result from discontinuing topical steroids used for as little as 2 months. Resultant signs/symptoms can last &gt;12 months, even with short duration of use. Clinicians and caregivers should be aware of this possible adverse effect of topical steroids and monitor the effects of topical steroids on infants/children, but more data are needed on this condition.

Systematic Review of the Topical Steroid Addiction and Topical Steroid Withdrawal Phenomenon in Children Diagnosed With Atopic Dermatitis and Treated With Topical Corticosteroids

Journal of the Dermatology Nurses’ Association 9(5):p 241-242, 9/10 2017. | DOI: 10.1097/JDN.0000000000000344

Exhaled breath profiles in the monitoring of loss of control and clinical recovery in asthma.

Asthma is a chronic inflammatory airway disease, associated with episodes of exacerbations. Therapy with inhaled corticosteroids (ICS) targets airway inflammation, which aims to maintain and restore asthma control. Clinical features are only modestly associated with airways inflammation. Therefore, we hypothesized that exhaled volatile metabolites identify longitudinal changes between clinically stable episodes and loss of asthma control. To determine whether exhaled volatile organic compounds (VOCs) as measured by gas-chromatography/mass-spectrometry (GC/MS) and electronic nose (eNose) technology discriminate between clinically stable and unstable episodes of asthma. Twenty-three patients with (partly) controlled mild to moderate persistent asthma using ICS were included in this prospective steroid withdrawal study. Exhaled metabolites were measured at baseline, during loss of control and after recovery. Standardized sampling of exhaled air was performed, after which samples were analysed by GC/MS and eNose. Univariate analysis of covariance (ANCOVA), followed by multivariate principal component analysis (PCA) was used to reduce data dimensionality. Next paired t tests were utilized to analyse within-subject breath profile differences at the different time-points. Finally, associations between exhaled metabolites and sputum inflammation markers were examined. Breath profiles by eNose showed 95% (21/22) correct classification for baseline vs loss of control and 86% (19/22) for loss of control vs recovery. Breath profiles using GC/MS showed accuracies of 68% (14/22) and 77% (17/22) for baseline vs loss of control and loss of control vs recovery, respectively. Significant associations between exhaled metabolites captured by GC/MS and sputum eosinophils were found (Pearson r≥.46, P<.01). Loss of asthma control can be discriminated from clinically stable episodes by longitudinal monitoring of exhaled metabolites measured by GC/MS and particularly eNose. Part of the uncovered biomarkers was associated with sputum eosinophils. These findings provide proof of principle for monitoring and identification of loss of asthma control by breathomics.

Intermediate steroid withdrawal after renal transplantation and anti-HLA antibodies (HLA-Abs) development

IntroductionSteroid withdrawal in renal transplantation is desirable to avoid their adverse effects. However, by decreasing the immunosuppression, could lead to an increased risk for the development of HLA-Abs. ObjectiveEvaluate the relationship between steroid withdrawal and development of HLA-Abs in renal transplantation. MethodsWe analyzed sera by Luminex from 182 kidney transplants performed from 1998 to 2011, before and two years after transplantation. All the patients had a pretransplant PRA (panel reactive of antibodies) <20% by complement-dependent cytotoxicity (CDC) and maintenance immunosuppression with tacrolimus and mycophenolate mofetil (MMF). We compared a group of steroid withdrawal at 7 months (group-I; n=130) and another control with non-withdrawal (group-II; n=52). Results22 patients (16.9%) in group-I and 11 patients in group-II (21.1%) had HLA-Abs after two years (pNS). Despite excluding patients with PRA >20%, we detected HLA-Abs pretransplant by Luminex in 11.5% of patients in both groups, of which, 66.6%, versus 53% (p 0.058), developed new specificities, with a similar percentage of donor specific antibodies (DSA) in both groups (33.33% vs 36.36%), pNS. In the subgroup without pretransplant HLA-Abs (group-I; n=115, group-II; n=45), 6.08% developed de novo HLA-Abs, being DSA 3.4% (Group-I) versus 7.69% in group II with 3.84% DSA (pNS). ConclusionsSteroid withdrawal at 7 months of renal transplantation does not entail a higher risk in terms of HLA-Abs development in patients without pretransplant HLA-Abs and treatment with tacrolimus and MMF, although larger studies are needed to confirm these findings.

Establishment of monosex female production of sablefish (Anoplopoma fimbria) through direct and indirect sex control

Methods are needed for monosex production of sablefish (Anoplopoma fimbria) to capitalize on superior growth of females relative to males. This study aimed to characterize the system of sex determination and establish methods for both direct and indirect feminization of sablefish. Juvenile sablefish ~40mm fork length were fed diets containing 17β-estradiol (E2), 17α-methyltestosterone (MT), or ethanol vehicle alone (control) for 2months and then divided into subgroups either shifted to the control diet (E2- and MT-short (S) duration treatments) or maintained on steroid-treated diets for an additional 2months (E2- and MT-long (L) duration treatments). Fish were subsampled for gonadal histology at the midpoint and end of the dietary treatments and all remaining fish were individually tagged to monitor subsequent growth and gonadal development for 36months (post-treatment time points of 0, 4, 16, 24, and 36months). Control fish exhibited balanced (1:1) sex ratios. E2 treatment regardless of duration induced ovarian differentiation in 100% of the genotypic males (i.e., direct feminization), while only the MT-L treatment induced testicular differentiation in 100% of the genotypic females (i.e., generating “neomales”). A high proportion (89%) of MT-S genotypic females possessed intersex gonads, indicating short-term MT exposure was insufficient to induce complete sex reversal. Significant differences in sex-specific growth were apparent by 16months post-treatment and associated with gonadal phenotype; sablefish with ovaries outgrew those with testes, regardless of genotypic sex. Fish from the E2-S and -L and MT-L treatment groups maintained their respective feminized and masculinized states after steroid withdrawal, although MT-S treated genotypic females tended to show further masculinization post-treatment. Upon reaching sexual maturity, control males and neomales were crossed with wild-caught female broodstock. Resultant embryos from control crosses were 54.6±8.9% (mean±SD) genotypic female, while those from neomale-female crosses were 100±0.0% genotypic female. Following sex differentiation, gonadal histology demonstrated that offspring from control crosses had a balanced phenotypic sex ratio, whereas all neomale offspring developed normal ovaries. This study establishes that sablefish utilize an XX/XY system of sex determination and methods for both direct and indirect monosex female production.

Ichthyosis linearis circumflexa with bamboo hair: challenges in the diagnosis and management

A 15-year-old boy had persistent and refractory erythroderma since early childhood. His parents noticed polycyclic skin lesions and hair fragility around the age of 5 years. He was treated by...

From dizziness to severe ataxia and dysarthria: New cases of anti-Ca/ARHGAP26 autoantibody-associated cerebellar ataxia suggest a broad clinical spectrum

In 2010, a novel anti-neuronal autoantibody, termed anti-Ca, was described in a patient with subacute cerebellar ataxia, and Rho GTPase-activating protein 26 (ARHGAP26) was identified as the target antigen. Recently, three additional cases of anti-Ca-positive cerebellar ataxia have been published. In addition to ataxia, cognitive decline and depression have been observed in some patients. Here, we report two new cases of anti-Ca-associated autoimmune cerebellar ataxia.Patient 1 presented with dizziness and acute yet mild limb and gait ataxia. Symptoms stabilized with long-term oral corticosteroid therapy but transiently worsened when steroids were tapered. Interestingly, both initial occurrence and worsening of the patient's neurological symptoms after steroid withdrawal were accompanied by spontaneous cutaneous hematomas. Patient 2 initially presented with an increased startle response and myoclonic jerks, and subsequently developed severe limb and gait ataxia, dysarthria, oculomotor disturbances, head and voice tremor, dysphagia, cognitive symptoms and depression. Steroid treatment was started five years after disease onset. The symptoms then responded only poorly to corticosteroids. At most recent follow-up, 19 years after disease onset, the patient was wheelchair-bound.These cases extend the clinical spectrum associated with anti-ARHGAP26 autoimmunity and suggest that early treatment may be important in patients with this rare syndrome.

Azathioprine allows glucocorticoid withdrawal - post hoc results of a prospective study in patients with inflammatory bowel diseases.

Background Azathioprine is recommended as first-line immunosuppressant in patients with steroid-dependent inflammatory bowel diseases (IBDs). However, data on steroid withdrawal after induction therapy in IBD patients are sparse. Methods In this post-hoc analysis of a prospective multicenter study, we analyzed the proportion and clinical characteristics of 324 azathioprine-tolerant patients as to whether they could terminate the glucocorticoid therapy after initiation of treatment with azathioprine. Results Systemic steroid therapy was required in 190 patients (58.6 %) at baseline and in 40 patients (12.3 %) at the end of the follow-up period (p < 0.001). The median daily dose was 30 mg at baseline and 10 mg at follow-up. At baseline, only 122 patients (37.2 %) were advised to take at least the lowest recommended dose of 2 mg/kg per day. At follow-up, 221 patients (68.2 %) were prescribed at least the recommended maintenance dosage. Conclusion The majority of patients with thiopurine-naïve IBDs that needed systemic steroids at baseline were able to discontinue steroids after 3 - 6 months of azathioprine therapy. These data support the continued high value of azathioprine in the immunosuppressive therapy of IBD.

Benefits of rituximab as a second-line treatment for autoimmune haemolytic anaemia in children: a prospective French cohort study.

Childhood autoimmune haemolytic anaemia (AIHA) requires second-line immunosuppressive therapy in 30-50% of cases. It appears that rituximab is indicated in such circumstances. This prospective national study reports the practice, efficacy and tolerance of rituximab in children with isolated AIHA and AIHA in the setting of Evans syndrome (ES). Sixty-one children were given rituximab between 2000 and 2014. The median interval from diagnosis to rituximab was 9·9 [interquartile range (IQR) 1·6-28·5] months. Forty-six patients responded (75%) and the 6-year relapse-free survival (RFS) was 48%. Twenty patients relapsed at a median interval of 10·8 (IQR 3·9-18·7) months, rituximab allowed steroid withdrawal in 44/61 (72%) of children. In isolated AIHA, complete response and 6-year RFS were significantly higher than in ES (P<0·05). Ten out of 61 patients were infants, seven of who responded with a 6-year RFS of 71%. Among patients without immunoglobulin substitution before rituximab, 4 are still receiving substitutions. Five patients died, including one potentially attributable to rituximab. This large observational series of childhood AIHA established the rituximab benefit-risk ratio, allowing steroid withdrawal, with 37% of long-term responders, mainly in isolated AIHA. All subgroups of patients drew benefit. Our long-term results indicate the baseline to be challenged by new treatment approaches.

Steroid free immunosuppression is associated with enhanced Th1 transcripts in kidney transplantation

BackgroundSteroid avoidance in immunosuppression in kidney transplantation offers several metabolic advantages, however it is associated with higher early acute rejection rate. Cellular and molecular mechanisms of this phenomenon remain poorly understood. MethodsIn this single center observational study, low-risk kidney transplant recipients randomized into large multicenter prospective ADVANCE trial with steroid avoidance/early withdrawal and center standard of care treated patients were monitored for 12months. The expressions of 28 transcripts, associated with alloimmune response and operational tolerance, were evaluated in the peripheral blood using RT-qPCR at 0, 7, 14, 90 and 365 postoperative days (POD) and in the protocol graft biopsy at 3months while lymphocyte subpopulations were analyzed by flow-cytometry within the follow-up. ResultsBoth steroid avoidance and withdrawal regimens were associated with significantly higher granzyme B (GZMB) transcript at POD 14 and perforin 1 (PRF1) transcript at POD 7. The higher interleukin 2 (IL-2) expression at POD 7 was detected only in the steroid avoidance group. Initial steroids decreased the expression SH2D1B transcript at POD14 and there were no further differences in other operational tolerance transcripts among groups. The statistically significant decrease in absolute numbers of peripheral NK cells in the first 14days was observed in the standard of care group only. There were no differences in analyzed intrarenal transcripts in 3-month biopsies among groups. ConclusionsThe enhanced expression of some of Th1 associated transcripts and limited effects on NK cells of steroid avoidance immunosuppression suggest higher susceptibility for early acute rejection.

Intermediate steroid withdrawal after renal transplantation and anti-HLA antibodies (HLA-Abs) development

IntroductionSteroid withdrawal in renal transplantation is desirable to avoid their adverse effects. However, by decreasing the immunosuppression, could lead to an increased risk for the development of HLA-Abs. ObjectiveEvaluate the relationship between steroid withdrawal and development of HLA-Abs in renal transplantation. MethodsWe analyzed sera by Luminex from 182 kidney transplants performed from 1998 to 2011, before and two years after transplantation. All the patients had a pretransplant PRA (panel reactive of antibodies) <20% by complement-dependent cytotoxicity (CDC) and maintenance immunosuppression with tacrolimus and mycophenolate mofetil (MMF). We compared a group of steroid withdrawal at 7 months (group-I; n=130) and another control with non-withdrawal (group-II; n=52). Results22 patients (16.9%) in group-I and 11 patients in group-II (21.1%) had HLA-Abs after two years (pNS). Despite excluding patients with PRA >20%, we detected HLA-Abs pretransplant by Luminex in 11.5% of patients in both groups, of which, 66.6%, versus 53% (p 0.058), developed new specificities, with a similar percentage of donor specific antibodies (DSA) in both groups (33.33% vs 36.36%), pNS. In the subgroup without pretransplant HLA-Abs (group-I; n=115, group-II; n=45), 6.08% developed de novo HLA-Abs, being DSA 3.4% (Group-I) versus 7.69% in group II with 3.84% DSA (pNS). ConclusionsSteroid withdrawal at 7 months of renal transplantation does not entail a higher risk in terms of HLA-Abs development in patients without pretransplant HLA-Abs and treatment with tacrolimus and MMF, although larger studies are needed to confirm these findings.

Randomised controlled trial comparing ofatumumab to rituximab in children with steroid-dependent and calcineurin inhibitor-dependent idiopathic nephrotic syndrome: study protocol

IntroductionOral steroids induce remission in about 90% of children with idiopathic nephrotic syndrome (INS), which is characterised by severe proteinuria and hypoalbuminaemia. Some children become steroid-dependent (SD) and require addition...

Steroid withdrawal after renal transplantation: a retrospective cohort study

BackgroundImmunosuppressive regimens in renal transplantation frequently contain corticosteroids, but many centers withdraw steroids as a consequence of unwanted side effects of steroids. The optimal timing to withdraw steroids after transplantation, however, remains unclear. The aim of this study was to determine an optimal time point following kidney transplantation that is associated with reduced mortality without jeopardizing the allograft to allow safe discontinuation of steroids.MethodsWe conducted a retrospective cohort study and computed a concatenated landmark-stratified Cox supermodel to estimate hazard ratios and 95% confidence intervals for mortality and graft loss using dynamic propensity score matching to adjust for confounding by indication.ResultsA total of 6070 first kidney transplant recipients in the Austrian Dialysis and Transplant Registry who were transplanted between 1990 and 2012 were evaluated and classified according to steroid treatment status throughout follow-up after kidney transplantation; 2142 patients were withdrawn from steroids during the study period. Overall, 1131 patients lost their graft and 821 patients in the study cohort died. Steroid withdrawal within 18 months after transplantation was associated with an increased rate of graft loss compared to steroid maintenance during that time (6 months after transplantation: HR = 1.8; 95% CI, 1.3 to 2.6; 18 months after transplantation: HR = 1.3; 95% CI, 1.1 to 1.6; 24 months after transplantation: HR = 1.2; 95% CI, 0.9 to 1.5), while mortality was not different between groups.ConclusionsOur findings suggest that steroid withdrawal after anti-IL-2 induction in the first 18 months after transplantation is associated with an increased risk of allograft loss.

Polyclonal and monoclonal antibodies for induction therapy in kidney transplant recipients.

Polyclonal and monoclonal antibodies for induction therapy in kidney transplant recipients.

Alemtuzumab Equalizes Short Term Outcomes in High Risk PRA Patients: Long Term Outcomes Suffer

Introduction: Alemtuzumab, a monoclonal antibody used in approximately 13% of kidney transplants, allows for early glucocorticoid withdrawal. High risk patients, defined by a presence of elevated Panel Reactive Antibody (PRA), are at greater risk for rejection, poorer graft outcomes, and have been shown to benefit from induction with alemtuzumab. The aim of this study is to assess the outcomes of immunologically sensitive kidney transplant recipients after induction with alemtuzumab and early steroid withdrawal. Methods: A retrospective analysis of 668 transplant recipients, all receiving alemtuzumab induction, from March 2006 through November 2015 was performed. High risk patients (defined as elevated PRA >20%) were compared to those with a low PRA (PRA <20%). Outcomes, such as patient survival, graft survival, and rejection were assessed. Results: Death-censored graft survival at 1-year was greater than 90% for both groups (p=0.343). Graft survival at 3- and 5- years was significantly lower in the high PRA group (3 years: 79.3%, 5 years: 73.2%) compared to the low PRA group (3 years: 91.3%, 5 years: 85.9%) (p=0.003, p=0.013). Overall death-censored graft survival for the high PRA group (77.6%) was also significantly lower than the low PRA group (87.5%, p=0.007). We noted no statistical difference between groups for other negative outcomes such as patient death or delayed graft function. Conclusion: Alemtuzumab and subsequent steroid withdrawal is effective at reducing short term poor outcome disparities between high PRA and low PRA recipients. However, graft survival after the second year, and increasing rejection rates prior to the fifth year, demonstrates that the short term effectiveness of alemtuzumab does not translate into long term graft maintenance in patients with elevated PRA. This evidence suggests further investigation into the effectiveness of alemtuzumab induction with steroid withdrawal regimens in patients with an elevated PRA.

Stress induces equivalent remodeling of hippocampal spine synapses in a simulated postpartum environment and in a female rat model of major depression

Stress and withdrawal of female reproductive hormones are known risk factors of postpartum depression. Although both of these factors are capable of powerfully modulating neuronal plasticity, there is no direct electron microscopic evidence of hippocampal spine synapse remodeling in postpartum depression. To address this issue, hormonal conditions of pregnancy and postpartum period were simulated in ovariectomized adult female Sprague–Dawley rats (n=76). The number of hippocampal spine synapses and the depressive behavior of rats in an active escape task were investigated in untreated control, hormone-withdrawn ‘postpartum’, simulated proestrus, and hormone-treated ‘postpartum’ animals. After ‘postpartum’ withdrawal of gonadal steroids, inescapable stress caused a loss of hippocampal spine synapses, which was related to poor escape performance in hormone-withdrawn ‘postpartum’ females. These responses were equivalent with the changes observed in untreated controls that is an established animal model of major depression. Maintaining proestrus levels of ovarian hormones during ‘postpartum’ stress exposure did not affect synaptic and behavioral responses to inescapable stress in simulated proestrus animals. By contrast, maintaining pregnancy levels of estradiol and progesterone during ‘postpartum’ stress exposure completely prevented the stress-induced loss of hippocampal spine synapses, which was associated with improved escape performance in hormone-treated ‘postpartum’ females. This protective effect appears to be mediated by a muted stress response as measured by serum corticosterone concentrations. In line with our emerging ‘synaptogenic hypothesis’ of depression, the loss of hippocampal spine synapses may be a novel perspective both in the pathomechanism and in the clinical management of postpartum affective illness.