Symptom Response to Low-Dose Naltrexone in Fibromyalgia: An Exploratory Analysis of the Randomized Placebo-Controlled FINAL Trial

The steroid metabolome in women with premenstrual dysphoric disorder during GnRH agonist-induced ovarian suppression: effects of estradiol and progesterone addback

Clinical evidence suggests that symptoms in premenstrual dysphoric disorder (PMDD) reflect abnormal responsivity to ovarian steroids. This differential steroid sensitivity could be underpinned by abnormal processing of the steroid signal. We used a pharmacometabolomics approach in women with prospectively confirmed PMDD (n=15) and controls without menstrual cycle-related affective symptoms (n=15). All were medication-free with normal menstrual cycle lengths. Notably, women with PMDD were required to show hormone sensitivity in an ovarian suppression protocol. Ovarian suppression was induced for 6 months with gonadotropin-releasing hormone (GnRH)-agonist (Lupron); after 3 months all were randomized to 4 weeks of estradiol (E2) or progesterone (P4). After a 2-week washout, a crossover was performed. Liquid chromatography/tandem mass spectrometry measured 49 steroid metabolites in serum. Values were excluded if >40% were below the limit of detectability (n=21). Analyses were performed with Wilcoxon rank-sum tests using false-discovery rate (q

Premenstrual Dysphoric Disorder Symptoms Following Ovarian Suppression: Triggered by Change in Ovarian Steroid Levels But Not Continuous Stable Levels | American Journal of Psychiatry

Objective:Premenstrual dysphoric disorder (PMDD) symptoms are eliminated by ovarian suppression and stimulated by administration of ovarian steroids, yet they appear with ovarian steroid levels indistinguishable from those in women without PMDD. Thus, ...

5α-Reductase Inhibition Prevents the Luteal Phase Increase in Plasma Allopregnanolone Levels and Mitigates Symptoms in Women with Premenstrual Dysphoric Disorder

Changes in neurosteroid levels during the luteal phase of the menstrual cycle may precipitate affective symptoms. To test this hypothesis, we stabilized neurosteroid levels by administering the 5α-reductase inhibitor dutasteride to block conversion of progesterone to its neurosteroid metabolite allopregnanolone in women with premenstrual dysphoric disorder (PMDD) and in asymptomatic control women. Sixteen women with prospectively confirmed PMDD and 16 control women participated in one of two separate randomized, double-blind, placebo-controlled, cross-over trials, each lasting three menstrual cycles. After one menstrual cycle of single-blind placebo, participants were randomized to receive, for the next two menstrual cycles, either double-blind placebo or dutasteride (low-dose 0.5 mg/day in the first eight PMDD and eight control women or high-dose 2.5 mg/day in the second group of women). All women completed the daily rating form (DRF) and were evaluated in clinic during the follicular and luteal phases of each menstrual cycle. Main outcome measures were the DRF symptoms of irritability, sadness, and anxiety. Analyses were performed with SAS PROC MIXED. In the low-dose group, no significant effect of dutasteride on PMDD symptoms was observed compared with placebo (ie, symptom cyclicity maintained), and plasma allopregnanolone levels increased in women with PMDD from follicular to the luteal phases, suggesting the absence of effect of the low-dose dutasteride on 5α-reductase. In contrast, the high-dose group experienced a statistically significant reduction in several core PMDD symptoms (ie, irritability, sadness, anxiety, food cravings, and bloating) on dutasteride compared with placebo. Dutasteride had no effect on mood in controls. Stabilization of allopregnanolone levels from the follicular to the luteal phase of the menstrual cycle by blocking the conversion of progesterone to its 5α-reduced neurosteroid metabolite mitigates symptoms in PMDD. These data provide preliminary support for the pathophysiologic relevance of neurosteroids in this condition.

The 2022 hormone therapy position statement of The North American Menopause Society

Abstract “The 2022 Hormone Therapy Position Statement of The North American Menopause Society” (NAMS) updates “The 2017 Hormone Therapy Position Statement of The North American Menopause Society” and identifies future research needs. An Advisory Panel of clinicians and researchers expert in the field of women’s health and menopause was recruited by NAMS to review the 2017 Position Statement, evaluate new literature, assess the evidence, and reach consensus on recommendations, using the level of evidence to identify the strength of recommendations and the quality of the evidence. The Advisory Panel’s recommendations were reviewed and approved by the NAMS Board of Trustees. Hormone therapy remains the most effective treatment for vasomotor symptoms (VMS) and the genitourinary syndrome of menopause and has been shown to prevent bone loss and fracture. The risks of hormone therapy differ depending on type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used. Treatment should be individualized using the best available evidence to maximize benefits and minimize risks, with periodic reevaluation of the benefits and risks of continuing therapy. For women aged younger than 60 years or who are within 10 years of menopause onset and have no contraindications, the benefit-risk ratio is favorable for treatment of bothersome VMS and prevention of bone loss. For women who initiate hormone therapy more than 10 years from menopause onset or who are aged older than 60 years, the benefit-risk ratio appears less favorable because of the greater absolute risks of coronary heart disease, stroke, venous thromboembolism, and dementia. Longer durations of therapy should be for documented indications such as persistent VMS, with shared decision-making and periodic reevaluation. For bothersome genitourinary syndrome of menopause symptoms not relieved with over-the-counter therapies in women without indications for use of systemic hormone therapy, low-dose vaginal estrogen therapy or other therapies (eg, vaginal dehydroepiandrosterone or oral ospemifene) are recommended.

Progesterone – Friend or foe?

Estradiol is the “prototypic” sex hormone of women. Yet, women have another sex hormone, which is often disregarded: Progesterone. The goal of this article is to provide a comprehensive review on progesterone, and its metabolite allopregnanolone, emphasizing three key areas: biological properties, main functions, and effects on mood in women. Recent years of intensive research on progesterone and allopregnanolone have paved the way for new treatment of postpartum depression. However, treatment for premenstrual syndrome and premenstrual dysphoric disorder as well as contraception that women can use without risking mental health problems are still needed. As far as progesterone is concerned, we might be dealing with a two-edged sword: while its metabolite allopregnanolone has been proven useful for treatment of PPD, it may trigger negative symptoms in women with PMS and PMDD. Overall, our current knowledge on the beneficial and harmful effects of progesterone is limited and further research is imperative.

What Patients Say Works (And Doesn't) for Migraines

For the live-updated, fully-labelled, interactive version of this infographic, click here. Eight of the top ten patient-reported treatments for Migraine are simple lifestyle changes, not drugs. CureTogether – a free resource owned by 23andMe that allows people to share information about their health and treatments – surveyed more than 6,000 people who self-identify as having […]

Dopamine Nation — Anna Lembke, MD

In Dopamine Nation, Dr. Anna Lembke, psychiatrist and author, explores the exciting new scientific discoveries that explain why the relentless pursuit of pleasure leads to pain.

Menopausal Hormone Therapy and Health Outcomes During the Intervention and Extended Poststopping Phases of the Women’s Health Initiative Randomized Trials

Manson and coauthors provide an update and overview of health outcomes during the intervention and poststopping phases of the Women’s Health Initiative (WHI) hormone therapy trials. In an accompanying Editorial, Nabel discusses how the WHI is a victory for women and their health.

Neuropsychiatric Systemic Lupus Erythematosus: A 2021 Update on Diagnosis, Management, and Current Challenges

Patients with systemic lupus erythematosus (SLE) experience neuropsychiatric symptoms. The term neuropsychiatric SLE (NPSLE) is a generic term that refers to a series of neurological and psychiatric symptoms directly related to SLE. In approximately 30% of patients with neuropsychiatric symptoms, SLE is the primary cause (NPSLE), and symptoms manifest more frequently around SLE onset. Neurovascular and psychotic conditions can also lead to NPSLE. Pathogenesis of NPSLE is implicated in both neuroinflammatory and ischemic mechanisms, and it is associated with high morbidity and mortality. After diagnosing and assigning causality, NPSLE treatment is individualized according to the type of neuropsychiatric manifestations, type of the predominant pathway, activity of SLE, and severity of the clinical manifestations. There are many problems to be addressed with regards to the diagnosis and management of NPSLE. Controlled clinical trials provide limited guidance for management, and observational cohort studies support symptomatic, antithrombotic, and immunosuppressive agents. The purpose of this review was to provide a detailed and critical review of the literature on the pathophysiology, diagnosis, and treatment of NPSLE. This study aimed to identify the shortcoming in diagnostic biomarkers, novel therapies against NPSLE, and additional research needs.

Application of a Systems Pharmacology‐Based Placebo Population Model to Analyze Long‐Term Data of Postmenopausal Osteoporosis

Osteoporosis is a progressive bone disease characterized by decreased bone mass resulting in increased fracture risk. The objective of this investigation was to test whether a recently developed dise...

Risks and Benefits of HRT Versus ERT in Order to Separate HRT from ERT

Aim: While the benefits of Hormone Replace Therapy (HRT) and Estrogen Replace Therapy (ERT) might overlap, their risks have to be separated particularly with regard to breast cancer. The risks of HRT are mainly Coronary Heart Disease (CHD) and Breast cancer. The main risk of ERT is the incidence of strokes which can be avoided by not using an oral estrogen but an Intra-uterine contraceptive but reducing the risk of endometrial cancer in women with a womb. Methods: Studies that randomized peri-menopausal and menopausal women to either HRT or ERT versus placebo and one study that included similar women followed up prospectively for the incidence of the development of Alzheimer’s Dementia (AD). Results: The significant risks of HRT included CHD, stroke and pulmonary embolism. The risk of breast cancer only really existed after long term follow-up [(annualized incidence, 0.45% vs 0.36%; Hazard Ratio (HR) 1.28)]. The significant risks of ERT only included strokes. There was a lower risk of breast cancer in the long term [HR 0.77, 95% CI 0.62–0.95; p=0.02]. Conclusions: In women with a uterus, where HRT instead of ERT is mandated, the oral progestogen of HRT can be replaced by intrauterine device loaded with a Progestogen. Similarly, the oral Estrogen of HRT and ERT can be replaced by Estrogen sources like the patch, gel or implants that bypass the liver and bypass potential problems like strokes and pulmonary embolism.

When Women Initiate Estrogen Therapy Matters | The Menopause Society

New large-scale analysis shows potential long-term benefits of initiating hormones during perimenopause

How easy is it to get addicted to methylphenidate?

Hi so I (18m) will start taking prescripted methylphenidate (medikinet) next thursday and i’ve never taken any stimulants (besides caffeine and…

The Consumer in Physical Pain: Implications for the Pain-of-Paying and Pricing

AbstractOver one in five Americans suffer from chronic pain—a figure that does not include other, milder, transient types of pain. Thus, there is abundant work exploring the influence of physical pain on physical and psychological welfare. However, there is no work regarding how physical pain influences consumption decisions, which is important because people in physical pain still buy products and make purchases. Give that physical pain “demands” attention, we suggest that consumers in physical pain (vs. those who are not) feel the pain-of-paying less, thereby increasing their purchase intentions and willingness-to-pay for products. We find evidence for our hypothesis in four studies with field and lab assessments of physical pain. We discuss the contributions and limitations of our work. We also highlight several implications that concern pricing decisions for marketers.