More On Prolactin Benefits!

The drug Risperdal/Risperidone is an immune modulator as it enhances the hormone prolactin.
So, this is working in a way similar to Low Dose Naltrexone, although through a different hormone.

Prolactin - "contribute to maturation as well as functioning of the immune cells"  "maintaining balance within immune reactions". 

When I was highly inflamed, before I took Low Dose Naltrexone, my prolactin level was low normal for post-menopausal women.  My eyes were very dry.  The Risperdal at a low dose helped with the dry eyes, possibly modulating my immune response.

"Prolactin/PL gene polymorphisms have now been shown to be linked to RA (Rheumatoid Arthritis). Thus, manipulation of PL may have significant clinical utility."   (Annals of NY Academy of Sciences, 1999)

"Since hyperprolactinemia and hypoprolactinemia are both immunosuppressive, physiological levels of circulating PRL must be necessary to maintain normal immunocompetence. Moderate increases in PRL during immune stimulation of the hypothalamic-pituitary axis may counteract glucocorticoid inhibition, whereas inappropriate prolongation of PRL synthesis could lead to autoimmune diseases. Increased release of PRL by the pituitary during stress may inhibit NK cell antitumor cytotoxicity. The variety of PRL isotypes, the existence of multiple receptor subunits, and the complexity of their intracellular signaling may explain the specificity of PRL action on different target cells."  (Neuroimmunmodulation, 1997)

Other studies show that too much prolactin, or "oversupply",  is also not good.  Oversupply maps to disease activity for SLE, celiac and possibly others.

Our family dosage is very small (.5 mg Risperdal or less), and the testing shows my prolactin to be at just above "post menopausal normal range".   I get tearing in my eyes when my risperdal (prolactin) dose is too high, so that serves me well in understanding how much to take.

Below you will find a 2010 abstract that describes the effects of prolactin and possible impacts on autoimmune disease.

Pregnenolone:  Fountain of Youth?

I found this image as I was sorting through images for the steroid pathways.  This is from a MacMillan publishing article.

More Support for LDN/Risperdal/Prolactin Hormone

The hormone Prolactin is instrumental in myelination of the brain and the immune response!  We need to protect this hormone to protect our immune system and our brain.

PART 1:
Dr. Rhonda Patrick:  Found My Fitness

Here is an image from the video podcast that explains the positive impacts of heat stress like sauna.  There are many brain impacts -- neurogenerative and myelination.  Prolactin is increased by LDN.  (See my test results on the first page of this blog.)  Prolactin is also increased by Risperdal, Re: psychiatrist.  Dr. Patrick says: Prolactin increases the production of myelin.  There is hope!  Pretty cool.

I think we are on the right track.  :-)

(So sorry about Rhonda's funny, funny face.  I caught her off guard. :-)   )

    PART 2:
    And the Journal of Neuroscience, May 1 2001:

"Taken together, prolactin acting at brain level has to be considered as a novel regulator of both emotionality and HPA axis reactivity."

PART 3:

From the Society for Endocrinology, www.yourhormones.info, 2015:

Definition:  Prolactin is a hormone produced in the pituitary gland, named because of its role in lactation. It also has other wide ranging functions in the body from acting on the reproductive system to influencing behaviour and regulating the immune system.

"Most people with low prolactin levels do not have any specific medical problems, although preliminary evidence suggests they might have reduced immune responses to some infections.

CONCLUSION:  Since estrogen also plays a role in modulating prolactin, my use of Bio-HRT and my reduced dose in Spring 2013, may have seriously impacted my immune system!   This explains why I suddenly needed anxiety medicines for the first time at age 56!

I predict, the Bio-HRT doctors will add prolactin to the sex hormones they manage and monitor!  They should use immunological markers/infection evidence in the future for determining the efficacy of BioHRT and the proper dose for each individual.  

Wouldn't it be nice to have enough hormones to adequately support your body's response to infection?

Low Dose Naltrexone Reverses Inflammation

This was my feeling from the start.  Because I saw major differences in my entire endocrine system within two weeks of starting LDN at 1.5 mg nightly, the LDN must have been working on inflammation, not healing organs.  It let my organs do their job.  Then, the burst of energy I felt at 6 months may have been some healing combined with the increased dose of Natural Desiccated Thyroid hormone.

It has been 20 months since my first dose of LDN, and my thyroid hormones have been normal for 7 months!  Once again, I would not have found LDN if the Endocrinologist had been properly monitoring my dose of thyroid and sex hormones.  Lucky for me, I was forced to look for an additional solution as my Endocrinologist would not raise my NDT dose even though I had hypothyroid symptoms.

I also am grateful that I have learned so much about psychiatry, the thyroid, and the immune system.  No one really tells you that you need to manage stress medically to prevent autoimmune flares and chronic infection.

I started my LDN trial to see if I could reduce my reactions to grains and nightshade foods!  That didn't work entirely.  I have minimal reactions now, but I still avoid them to keep my health humming.

I had been able to manage my premenopausal years with diet, exercise, and a simple life.  Now I know that much more support is required once the ovaries go offline.  For some of us, it is not a natural state.  Greater measures are needed!

My recipe:
1.  Bioidentical HRT
2.  Paleo Autoimmune Protocol Diet
3.  Daily Exercise
4.  Low Dose Naltrexone

It works.  I am happy!


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Dig Dis Sci. 2011 Jul; 56(7): 2088–2097. 

Published online 2011 Mar 8. doi:  10.1007/s10620-011-1653-7

PMCID: PMC3381945

NIHMSID: NIHMS373349

Therapy with the Opioid Antagonist Naltrexone Promotes Mucosal Healing in Active Crohn’s Disease: A Randomized Placebo-Controlled Trial

Jill P. Smith, Sandra I. Bingaman, Francesca Ruggiero, David T. Mauger, Aparna Mukherjee, Christopher O. McGovern, and  Ian S. Zagon

Author information ► Copyright and License information ►

The publisher's final edited version of this article is available at Dig Dis Sci

See other articles in PMC that cite the published article.

Go to:

Abstract

Background

Endogenous opioid peptides have been shown to play a role in the development and/or perpetuation of inflammation. We hypothesize that the endogenous opioid system is involved in inflammatory bowel disease, and antagonism of the opioid–opioid receptor will lead to reversal of inflammation.

Aims

A randomized double-blind placebo-controlled study was designed to test the efficacy and safety of an opioid antagonist for 12 weeks in adults with active Crohn’s disease.

Methods

Forty subjects with active Crohn’s disease were enrolled in the study. Randomized patients received daily oral administration of 4.5-mg naltrexone or placebo. Providers and patients were masked to treatment assignment. The primary outcome was the proportion of subjects in each arm with a 70-point decline in Crohn’s Disease Activity Index score (CDAI). The secondary outcome included mucosal healing based upon colonoscopy appearance and histology.

Results

Eighty-eight percent of those treated with naltrexone had at least a 70-point decline in CDAI scores compared to 40% of placebo-treated patients (p = 0.009). After 12 weeks, 78% of subjects treated with naltrexone exhibited an endoscopic response as indicated by a 5-point decline in the Crohn’s disease endoscopy index severity score (CDEIS) from baseline compared to 28% response in placebo-treated controls (p = 0.008), and 33% achieved remission with a CDEIS score <6, whereas only 8% of those on placebo showed the same change. Fatigue was the only side effect reported that was significantly greater in subjects receiving placebo.

Conclusions

Naltrexone improves clinical and inflammatory activity of subjects with moderate to severe Crohn’s disease compared to placebo-treated controls. Strategies to alter the endogenous opioid system provide promise for the treatment of Crohn’s disease.

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.
_______________________________________________________________________________________________

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.

The Current Plan: Confirmed by Increased Energy! Feeling Normal Again!

Support Plan				5/20/15
		**Recently Added**
Diet (reduces attack on endocrine organs)	Basic Paleo Autoimmune Protocol Diet – AIP Antiinflammatory	No egg/ grain/nightshade/ dairy/legume/ seed  No nuts for 6mo	No gluten,  no flour, no sugar,bone broth, liver/ grass fed beef/wild caught Fish	Since Dec ‘13
Kefir Grains May support digestion and nerotransmitters	In coconut milk	Daily	Supportive Bacteria	Off year 2014
Thyroid Supported with natural hormone replacement, NDT	Hashimotos Autoimmune with many low endocrine Hormones. Anti Inflammatory	Naturethroid supplement @65mcg  Tsh=.5 Ft4 and Ft3 at the Top of normal Range Rt3=normal	Take on empty stomach with HCL/Pepsin to help digest. No food for 2 hrs.	Since January 2015
Ibuprofen	Two tabs once daily	Neuroprotective	Nightly	Intermittent
Bio HRT (if thyroid hormone is low, these are all too low!)	Topical Progesterone: Progest 18 mg, Testosterone 12 mg,Estradiol 12 mg, Pregnenalone dab	6 days/week Sunday+no hormones to clear all the receptors	Anti-inflammatory Bio HRT makes TSH value less reliable	Since Aug 2009
Adderall Generic	For inflammation related attention problems	Dose: 5 mg Every 4hrs	LDN allowed me to lower this dose	Since infection 2013
Now Super Enzymes	Each meal/ 2 tabs	Low thyroid leads to low stomach enzymes	Helps stomach empty	Since Dec 2013
Vitamin D	5000 mg	Immune, pro hormone - supports hormone conversion	With food/Trader Joe brand has no soy	Since Feb 2015
Vitamin C	1000 mg	Immune	With food	Since 2009
B12- methyl	5000 mg	Immune	With food	Since Feb 2015
EPA/DHA/ Vits D, A, K	Brain health, via cod liver oil  1 TBLSP	Immune Antiinflammatory	With food	Since Spring 2014
Selenium	200 mg	Improves thyroid hormones	Nightly	Since Feb 2015
Prescript Assist	Soil probiotic	Immune	Sundays	Since Sept 2014
Risperdal (improves mood through seratonin & dopamine)-- stops cognitive decline--assist learning and memory	General Support, need more if eat reactive foods.  Dopamine improves thyroid hormones. Regulates sleep.	.25 - .5  mg I need more if I ever slip and eat grains.  Anxiety goes up.	Nightly Creates natural hormone Prolactin at post-menopause levels	Since Oct 2014
Low Dose Naltrexone FROM FUNCTIONAL MEDICINE DOCTOR	Inflammation Immune Support Pain reduction Improves ALL hormones	3.0 mg nightly	Nightly	Since Nov 2013
Exercise	60 minutes Daily Inflammation	Walking/Running	increases food absorption and hormones, affects gene expression	Since March 2009
5- HTP	100 mg Mood/Sleep	Mood, attention, sleep. Precursor to Serotonin	Nightly	Since Oct 2014