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.     

Isolation and identification of three new chromones from the leaves of Pimenta dioica with cytotoxic,oestrogenic and anti-oestrogenic effects

Context: Pimenta dioica (L.) Merr. (Myrtaceae) is used in Costa Rican traditional medicine for women’s health. Our previous work showed that P. dioica extracts were oestrogenic.

Objectives: This work identifies phytochemicals from P. dioica that are responsible for the plant’s oestrogen-like activities.

Materials and methods: P. dioica leaves were collected in Costa Rica in 2005. Fractions resulting from chromatographic separation of a methanol extract were tested at 50?μg/mL in a competitive oestrogen receptor-binding assay. Active compounds were isolated by HPLC and identified by NMR and MS. Pure compounds were tested at 1?μM in the oestrogen-responsive SEAP reporter gene assay. The effects on cell viability, cytotoxicity and apoptosis were investigated in breast cancer (MCF-7 and SK-BR3) and gastric cancer (AGS and NCI-N87) cell lines using the ApoTox-Glo and Caspase-Glo assays and qPCR.

Results: Quercitrin and three new chromones, including a 2-phenoxychromone, 6,8-di-C-methylcapillarisin (1) were isolated and identified. Compound 1 caused a 6.2-fold increase in SEAP expression at 1?μM (p?2 caused a 6.0-fold increase in SEAP, inhibited the growth of MCF-7, AGS and NCI-N87 cells (IC₅₀ 54.27, 38.13 and 51.22?μg/mL, respectively), and induced apoptosis via caspase 8 and increased the Bax/Bcl-2 mRNA ratio in MCF-7 cells. Compound 3 was anti-oestrogenic in MCF-7 cells.

Discussion and conclusions: Compounds from P. dioica have oestrogenic, anti-oestrogenic and cytotoxic effects that may explain the ethnomedical use of this plant.     

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.     

The influence of phytoestrogens on different physiological and pathological processes: An overview

Functional foods have nutritional properties and organic functions, which are beneficial to health. Certain types of functional food components are so‐called phytoestrogens, non‐steroidal compounds derived from the metabolism of precursors contained in plants, which originate secondary metabotypes known to induce biological responses and by mimicry or modulating the action of endogenous estrogen. These molecules are involved in several physiological and pathological processes related to reproduction, bone remodeling, skin, cardiovascular, nervous, immune systems, and metabolism. This review aimed to present an overview of phytoestrogens regarding their chemical structure, actions, and effects in the organism given several pathologies. Several studies have demonstrated beneficial phytoestrogen actions, such as lipid profile improvement, cognitive function, menopause, oxidative stress, among others. Phytoestrogens effects are not completely elucidated, being necessary future research to understand the exact action mechanisms, whether they are via estrogen receptor or whether other hidden mechanisms produce these effects. Thus, this review makes a general approach to the phytoestrogen actions, beneficial effects, risk and limitations. However, the complexities of biological effects after ingestion of phytoestrogens and the differences in their metabolism and bioavailability indicate that interpretation of either risk or benefits needs to be made with caution.     

HCV感染与肾移植后糖尿病关系的荟萃分析

目的应用荟萃分析系统评价HCV感染是否为肾移植后糖尿病(PTDM)的相关危险因素。 方法系统检索中国期刊全文数据库、中国生物医学数据库、PubMed数据库、Embase数据库、Google scholar和Web of science database截至2019年12月公开发表的相关文献。应用Stata 15.1统计软件使用随机效应模型进行荟萃分析,计算相对危险度(RR)。 结果共纳入22篇文献,包含129 981例肾移植受者。荟萃分析结果显示,HCV感染的肾移植受者术后发生PTDM的风险为非HCV感染者的2.5倍(RR＝2.50, 95%CI: 1.95～3.20, P<0.001)。在亚洲、高加索和美洲人种中,HCV感染均为肾移植术后PTDM的危险因素。 结论HCV感染是促进肾移植术后发生PTDM的危险因素,感染者需尽早进行清除HCV的相关治疗。     

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.