Effects of Menopause on Autoimmune Diseases

Miranda A Farage, Kenneth W Miller, Howard I Maibach

    Expert Rev of Obstet Gynecol. 2012;7(6):557-571.Â

   (from Medscape) 2015

<<<  Excerpts:  I chose these to stress the link between hormones and autoimmune disease.  I am genetically susceptible to Rheumatoid Arthritis, so I also included some of the section on RA. >>>>>>

Postmenopausal deficits in estrogen and progesterone, and the replacement of E2, the primary

estrogen of the reproductive years, to E1 carry impact far beyond the immune system.

The sudden and dramatic removal of estrogen from the female body, particularly in the form of estradiol, is a veritable tsunami with significant and largely negative effects on many body tissues, including a loss of skin integrity and tone, poorer muscle tone

-- (affecting heart, vasculature, eye and bladder function; declining brain function; and deterioration in bone strength). 

Estrogen levels, and particularly the estrogen withdrawal of menopause, undeniably impact autoimmunity in women as well.

The molecular and cellular changes associated with aging have substantial clinical ramifications. The elderly have impaired ability to achieve immunization but much higher levels of circulating autoantibodies, (due to the lack of naive effectors) impaired response to viral infections, increased risk of bacterial infections, and increased risk of both neoplastic and autoimmune disease.

Androgens, estrogen, and progesterone ALL influence immune functions; estrogen in the form of 17b estradiol has been particularly associated with profound influences on the immune system.

Anti-nuclear antibodies levels remain constant until approximately 60 years, and then rise.

Rhuematoid Arthritis

Menopause is associated with an increased risk of disease onset. In a cohort of nearly 32,000 women in Iowa (USA), those who reached menopause before 45 years of age had a higher risk of RA than women who reached menopause after 51 years of age.[90] Similar results were obtained in a study that evaluated 18,326 Swedish women and compared those who entered menopause before 45 to those who reached menopause after 45 years of age.[91]  

Another author followed RA patients over a 6-year period; the 209 female patients evaluated were divided into premenopausal and postmenopausal groups. Postmenopausal subjects had greater joint damage as measured radiographically as well as by health assessment questionnaires. In addition, comparison with both premenopausal women and men determined that estrogen deprivation of menopause was a significant factor in the disparity of damage between men and women.[92]   Although the use of HRT does not appear to influence the risk of developing RA,[93] HRT improves both symptoms and progression of disease.[94]

This review revealed a disturbing absence of data on the influence of menopause on autoimmune disease given its predominance in women and the fact that autoimmunity increases with age, an absence possibly related to an existing deficit in the understanding of the physiological basis for autoimmune disease in general.

<<<<<   Low Dose Naltrexone is an immune modulator.  
Low Dose Naltrexone stimulates maturation of the DC's (Dendritic Cells) shown above.  I felt this impact within 2 weeks of taking LDN.  >>>>>

The Brain:Protect It

The Brain:  Hormones Affect Workings

I am not a neurologist or brain surgeon, but I do spend time learning about the brain.  So let me just share some key learnings.  

1.  Low Thyroid Hormones
-- correlate with depression
-- correlate with slower thinking
-- can be caused by inflammation and a low producing pituitary TSH
-- can drive all the other hormones lower -- that's at least 40!
-- hormone supplements can be more efficacious with added stomach enzymes with dosage
-- can be affected by amount of bio-hrt, supplements, foods, elevation, dopamine, stress, herbs, medicines, low-dose naltrexone, seasons *, weight, etc. 
-- can be tested every 4 weeks
-- psychiatry:  proper thyroid support can reduce or eliminate needs for other meds
-- psychiatry:  the brain is a "use it or lose it" organ, do not leave it untreated

2.  Sleep
-- is protective for creating proper neurotransmitters
-- is disrupted by autoimmune reactivity
-- sleep medicines often do not work -- just a band-aid over symptoms
--  is promoted by hormone balance

3.  Depression
--  can change the brain permanently
--  can be induced by medicines and anesthetic use
--  can be reduced by bio hrt

4.  Anxiety
--  linked to food reactions in autoimmune flares
--  Bio HRT does reduce anxiety:  especially allopregnanolone and progesterone*
--  Allopregnanolone hormone shown to impact BDNF-- brain regeneration*
--  Risperdal increases prolactin, like other atypical antipsychotics works on memory/learning**, it changes breathing to deeper breaths, lowers stress and boosts immunity

5.  Cortisol/Stress
--  changes the brain 
--  reduced with CBT, DBT, exercise, music, breathing, singing, laughter, pets, family support, self understanding, peer support, etc.  
--  affected strongly by early life experiences
--  reduces the body's ability to fight infection 


In short, brain health matters!   Of course good parenting helps.   But it is not all parenting.   There are biological elements to manage. 


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*

The researchers from the University of Cambridge analyzed genes from more than 16,000 people from both the northern and southern hemispheres. They found that the activity of nearly one-quarter of the genes differed according to the time of the year — some are more active in winter, others are more active in summer. Seasons also affect our immune cells, and the composition of our blood and fat, according to the findings of the study, which was recently published in the journal Nature Communications.
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Prog Neurobiol. 2014 Feb;113:79-87. doi: 10.1016/j.pneurobio.2013.09.003. Epub 2013 Nov 8.

The role of allopregnanolone in depression and anxiety.

Schüle C1, Nothdurfter C2, Rupprecht R2.

Author information

1Department of Psychiatry and Psychotherapy, Ludwig-Maximilian-University, Nussbaumstr. 7, 80336 Munich, Germany. Electronic address: Cornelius.Schuele@med.uni-muenchen.de.

2Department of Psychiatry and Psychotherapy, University Regensburg, Universitätsstrasse 84, 93053 Regensburg, Germany.

Abstract

Neuroactive steroids such as allopregnanolone do not only act as transcriptional factors in the regulation of gene expression after intracellular back-oxidation into the 5-α pregnane steroids but may also alter neuronal excitability through interactions with specific neurotransmitter receptors. In particular, certain 3α-reduced metabolites of progesterone such as 3α,5α-tetrahydroprogesterone (allopregnanolone) and 3α,5β-tetrahydroprogesterone (pregnanolone) are potent positive allosteric modulators of the GABA(A) receptor complex. During the last years, the downregulation of neurosteroid biosynthesis has been intensively discussed to be a possible contributor to the development of anxiety and depressive disorder. Reduced levels of allopregnanolone in the peripheral blood or cerebrospinal fluid were found to be associated with major depression, anxiety disorders, premenstrual dysphoric disorder, negative symptoms in schizophrenia, or impulsive aggression. The importance of allopregnanolone for the regulation of emotion and its therapeutical use in depression and anxiety may not only involve GABAergic mechanisms, but probably also includes enhancement of neurogenesis, myelination, neuroprotection, and regulatory effects on HPA axis function. Certain pharmacokinetic obstacles limit the therapeutic use of natural neurosteroids (low bioavailability, oxidation to the ketone). Until now synthetic neuroactive steroids could not be established in the treatment of anxiety disorders or depression. However, the translocator protein (18 kDa) (TSPO) which is important for neurosteroidogenesis has been identified as a potential novel target. TSPO ligands such as XBD 173 increase neurosteroidogenesis and have anxiolytic effects with a favorable side effect profile.

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Prog Neuropsychopharmacol Biol Psychiatry. 2014 Jan 3;48:64-78. doi: 10.1016/j.pnpbp.2013.09.005. Epub 2013 Sep 14.

Multifunctional aspects of allopregnanolone in stress and related disorders.

Bali A1, Jaggi AS.

Author information

1Department of Pharmaceutical Sciences and Drug Research, Punjabi University Patiala, 147002, India.

Abstract

Allopregnanolone (3α-hydroxy-5α-pregnan-20-one) is a major cholesterol-derived neurosteroid in the central nervous system and is synthesized from progesterone by steroidogenic enzymes, 5α-reductase (the rate-limiting enzyme) and 3α-hydroxysteroid dehydrogenase. The pathophysiological role of allopregnanolone in neuropsychiatric disorders has been highlighted in several investigations. The changes in neuroactive steroid levels are detected in stress and stress-related disorders including anxiety, panic and depression. The changes in allopregnanolone in response to acute stressor tend to restore the homeostasis by dampening the hyper-activated HPA axis. However, long standing stressors leading to development of neuropsychiatric disorders including depression and anxiety are associated with decrease in the allopregnanolone levels. GABAA receptor complex has been considered as the primary target of allopregnanolone and majority of its inhibitory actions are mediated through GABA potentiation or direct activation of GABA currents. The role of progesterone receptors in producing the late actions of allopregnanolone particularly in lordosis facilitation has also been described. Moreover, recent studies have also described the involvement of other multiple targets including brain-derived neurotrophic factor (BDNF), glutamate, dopamine, opioids, oxytocin, and calcium channels. The present review discusses the various aspects of allopregnanolone in stress and stress-related disorders including anxiety, depression and panic.

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**
Risperdal -- atypical antipsychotic:  I use a "sub-theraputic dose" of .5 mg.

serotonin

5-HT7 is a type of receptor activated by the neurotransmitter serotonin. Some of the most potent effects of lurasidone (Latuda), an atypical antipsychotic with antidepressant effects in bipolar depression, and vortioxetine (Brintellix), a unique antidepressant for unipolar depression that also has positive effects on cognition, occur through the blockade of 5-HT7 receptors. The atypical antipsychotics aripiprazole and sulpiride also act on 5-HT7 receptors.

Researcher Agnieszka Nikiforuk summarized the research to date on 5-HT7 receptors in the journal CNS Drugs in 2015.

The receptors play a role in regulating sleep and circadian rhythms, which may explain why drugs that target them can be helpful in depression. Drugs that target 5-HT7 receptors have also improved learning and memory.

One subject of research into 5-HT7 receptors is whether better results come from blocking the receptors or stimulating them.

Blockade of 5-HT7 receptors has improved depression-like symptoms in animals and enhances the effects of sub-therapeutic doses of antidepressants. In other animal studies, stimulation of the receptors has appeared promising for the prevention of age-related cognitive decline.

Tags: 5-HT7 receptors, serotonin

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Regarding stress and infection.  This supports the use of Risperdal for immunity.

Introduction

In the inaugural issue, T lymphocyte function was established as an important topic for manuscripts to be published in Brain, Behavior, and Immunity (BBI). Volume 1, Issue 1, published in March of 1987, included a paper from Glaser et al. (Glaser et al., 1987) documenting that killing of Epstein-Barr virus (EBV) infected B lymphocytes by mononuclear cells (likely cytotoxic T cells) from EBV seropositive medical students was significantly diminished during periods of school examinations compared to baseline (non-examination) periods of time. Significant increases in psychological distress (as measured by the General Severity Index of the Brief Symptom Inventory) were also observed during periods of examination compared to non-examination.