Estrogen affects post-menopausal women differently than estrogen plus progestin replacement therapy

BACKGROUND: In the Women's Health Initiative Randomized Controlled Trial (WHI RCT), estrogen-only treatment compared with combined estrogen-progestin treatment resulted in less coronary artery disease, no increase in breast cancer and no reduction in colorectal cancer. Since we previously reasonably replicated the combined estrogen-progestin WHI RCT using the UK General Practice Research Database (GPRD), estrogen-only treatment was investigated using a similar methodology. METHODS: This GPRD study simulated the estrogen-only WHI RCT of women who had undergone a hysterectomy except for randomization. The primary analysis examined 11 572 unexposed and 6890 Exposed women (aged 55-79) treated with conjugated equine estrogen and was compared with the combined estrogen-progestin GPRD study. RESULTS: At baseline, women with a hysterectomy exhibited more cardiovascular disease than those with an intact uterus. In the estrogen-only GPRD study, adjusted hazard ratios (HRs) were 0.50 (0.38-0.67) for myocardial infarction (MI), 1.13 (0.91-1.41) for breast cancer, and 1.18 (0.72-1.92) for colorectal cancer. Compared to the HRs in the estrogen-progestin GPRD study, the estrogen-only results are significantly lower for MI and breast cancer and higher for colon cancer, a pattern similar to the WHI RCT study comparisons. CONCLUSIONS: This study confirms that post-menopausal women in the overall population respond differently to estrogen-only treatment compared with estrogen-progestin treatment, due to different hormone regimens and/or increased cardiovascular disease in hysterectomized women.     

A polymorphism in the AMH type II receptor gene is associated with age at menopause in interaction with parity

BACKGROUND: Anti-Müllerian hormone (AMH) inhibits primordial follicle recruitment in the mouse ovary. We hypothesize that in women AMH signaling also regulates the usage of the primordial follicle pool and hence influences the onset of menopause. Since age at menopause has a strong genetic component, we investigated the role of AMH signaling using a candidate gene approach. METHODS: In two large population-based cohorts of Dutch post-menopausal women (n = 2381 and n = 248), we examined the association between two polymorphisms, one in the AMH gene and one in the AMH type II receptor (AMHR2) gene, and natural age at menopause. RESULTS: The AMH Ile(49)Ser polymorphism (rs10407022) was not associated with age at menopause in either cohort. In the Rotterdam cohort, the AMHR2 -482 A > G polymorphism (rs2002555) was associated with age at menopause in interaction with the number of offspring (P = 0.001). Nulliparous women homozygous for the G-allele entered menopause 2.6 years earlier compared with nulliparous women homozygous for the A-allele (P = 0.005). In the LASA cohort, women with the G/G genotype tended to enter menopause 2.8 years earlier compared with the A/A genotype (P = 0.063). CONCLUSIONS: The observed association of the AMHR2 -482 A > G polymorphism with natural age at menopause suggests a role for AMH signaling in the usage of the primordial follicle pool in women.     

From the "climacteric disease" to the "male climacteric" The historical origins of a modern concept

The historical origins of the modern concept of a "male climacteric" have hitherto been traced to the late 19th and early 20th centuries. Based on a careful scrutiny of early modern and 19th-century sources, this paper shows that the concept goes back much further, however. It evolved from the ancient notion of critical "climacterical years" which recurred every 7th year throughout human life and from the concept of a predominantly male "climacteric disease" which Henry Halford put forward in 1813. In the course of the 19th century, this concept of a "climacteric disease" was gradually reframed under the influence of contemporary interest in the female "menopause" and eventually both largely merged into the single notion of a "climacteric" in both sexes. By 1900, the "climacteric" had become so strongly associated with the female sex that the observation of a "male climacteric" could be presented as a new finding, although the symptoms associated with it were, in retrospect, largely taken from the older notions of the "climacteric disease" and the female "menopause".     

Chronic traumatic stress and chronic pain in the majority world: notes towards an integrative approach

Post Traumatic Stress Disorder (PTSD) and chronic pain have been identified as global health challenges for health professionals, and there is a robust literature linking PTSD and chronic pain. Much of the research is focused on high-income countries, leaving a serious gap when chronic pain is considered globally. Using the concept of Continuous Traumatic Stress (CTS), we look at how broader social conditions impact on the experience of chronic pain. We review the relevant literature on chronic pain, PTSD, and CTS, and suggest a research agenda for a more globally relevant and contextual understanding of chronic pain.     

Hormonal management of migraine associated with menses and the menopause: a clinical review

OBJECTIVE: This article reviews hormonal strategies used to treat headaches attributed to the menstrual cycle or to peri- or postmenopausal estrogen fluctuations. These may occur as a result of natural ovarian cycles, or in response to the withdrawal of exogenously administered estrogen. BACKGROUND: A wide variety of evidence indicates that cyclic ovarian sex steroid production affects the clinical expression of migraine. This has led to interest in the use of hormonal treatments for migraine. METHODS: A PubMed search of the literature was conducted using the terms "migraine,"treatment,"estrogen,"hormones,"menopause," and "menstrual migraine." Articles were selected on the basis of relevance. RESULTS: The overarching goal of hormonal treatment regimens for migraine is minimization of estrogen fluctuations. For migraine associated with the menstrual cycle, supplemental estrogen may be administered in the late luteal phase of the natural menstrual cycle or during the pill-free week of traditional combination oral contraceptives. Modified contraceptive regimens may be used that extend the duration of active hormone use, minimize the duration or extent of hormone withdrawal, or both. In menopause, hormonally associated migraine is most likely to be due to estrogen-replacement regimens, and treatment generally involves manipulating these regimens. Evidence regarding the safety and efficacy of these regimens is limited. CONCLUSIONS: Hormonal treatment of migraine is not a first-line treatment strategy for most women with migraine. Evidence is lacking regarding its long term harms and migraine is a contraindication to the use of exogenous estrogen in all women with aura and those aged 35 or older. The harm to benefit balances of several traditional nonhormonal therapies are better established.     

Cushing’s disease: A single centre’s experience using the linear accelerator (LINAC) for stereotactic radiosurgery and fractionated stereotactic radiotherapy

Cushing’s disease is hypercortisolaemia secondary to an adrenocorticotrophic hormone secreting pituitary adenoma. Primary management is almost always surgical, with limited effective medical interventions available. Adjuvant therapy in the form of radiation is gaining popularity, with the bulk of the literature related to the Gamma Knife. We present the results from our own institution using the linear accelerator (LINAC) since 1990. Thirty-six patients who underwent stereotactic radiosurgery (SRS), one patient who underwent fractionated stereotactic radiotherapy (FSRT) and for the purposes of comparison, 13 patients who had undergone conventional radiotherapy prior to 1990, were included in the analysis. Serum cortisol levels improved in nine of 36 (25%) SRS patients and 24 hour urinary free cortisol levels improved in 13 of 36 patients (36.1%). Tumour volume control was excellent in the SRS group with deterioration in only one patient (3%). The patient who underwent FSRT had a highly aggressive tumour refractory to radiation.     

Aloud real- time reading of intensive care unit diaries: A feasibility study

ObjectivesMemories of frightening/delusional intensive care unit experiences are a major risk factor for subsequent psychiatric morbidity of critical illness survivors; factual memories are protective. Systematically providing factual information during initial memory consolidation could mitigate the emotional character of the formed memories. We explored feasibility and obtained stakeholder feedback of a novel approach to intensive care unit diaries whereby entries were read aloud to the patients right after they were written to facilitate systematic real time orientation and formation of factual memories.Research methodologyProspective interventional pilot study involving reading diary entries aloud. We have also interviewed involved stakeholders for feedback and collected exploratory data on psychiatric symptoms from patients right after the intensive care stay.SettingVarious intensive care units in a single academic center.Main outcome measuresFeasibility was defined as intervention delivery on ≥80% of days following patient recruitment. Content analysis was performed on stakeholder interview responses. Questionnaire data were compared for patients who received real-time reading to the historical cohort who did not.ResultsOverall, 57% (17 of 30) of patients achieved the set feasibility threshold. Following protocol adjustment, we achieved 86% feasibility in the last subset of patients. Patients reported the intervention as comforting and appreciated the reorientation aspect. Nurses overwhelmingly liked the idea; most common concern was not knowing what to write. Some therapists were unsure whether reading entries aloud might overwhelm the patients. There were no significant differences in psychiatric symptoms when compared to the historic cohort.ConclusionWe encountered several implementation obstacles; once these were addressed, we achieved set feasibility target for the last group of patients. Reading diary entries aloud was welcomed by stakeholders. Designing a trial to assess efficacy of the intervention on psychiatric outcomes appears warranted.Implications for Clinical PracticeThere is no recommendation to change current practice as benefits of the intervention are unproven.     

POST INSERTION CATHETER CARE IN PERITONEAL DIALYSIS (PD) CENTRES ACROSS EUROPE. PART 2: COMPLICATION RATES AND INDIVIDUAL PATIENT OUTCOMES

The first part of this report, which looked at centre policy, showed that there was no consensus on the best way to manage a patient in the rest period between PD catheter insertion and the first use of the catheter for dialysis. This paper intends to investigate if the differences in policy had any effect on complication rate and individual patient outcomes. Data were included from 298 patients of 49 participating centres. The results revealed a high rate of catheter related complications, with half of the patients having been treated for complications including leakage (29%), malfunction (23%) or infection (10%), and a quarter of patients having been hospitalised for catheter problems. Leakage was more frequently observed in lean and obese patients and if the catheter was only immobilized for a short time period. Diabetes, having constipation at first use and having rested for less than 6 hours after catheter insertion were significant risk factors for malfunction. Infection seemed to be related to the type of catheter used and hygienic precautions (not significant) and showed a significant relationship with the frequency of dressing changes. There is still an important lack of evidence on which to develop an optimal protocol for PD catheter insertion and care before first use.