windinthepines
Member
- Joined
- Feb 1, 2021
- Messages
- 127
[2017]
[Topical DHT]
It’s effective topically, but it might take several milligrams on the skin to absorb one mg.
[MS-like symptoms... including numbness in some finger tips, loss of dexterity in those same fingers, depression.]
Have you tried pregnenolone? DHT is probably safe, since it can’t turn into estrogen.
[DHEA turning to estrogen when taking a few mg]
I don’t think that’s a risk with 5 mg or less. Things that protect against aromatase include aspirin, thyroid, vitamin D, pregnenolone, and sugar.
[Thanks. Is there anything else I should try for sudden onset of possible MS-like symptoms (numbness in hands, clumsiness, mild visual distortion, memory problems)? I take thyroid, aspirin, pregnenolone, vitamin A. I just started taking more vitamin D, and using the chicken lights more.]
That list of symptoms reminds me of the first woman I knew who used progesterone for MS. She recovered completely, and gave a good lecture to my endocrinology class at the NCNM naturopathic school.
Iran J Med Sci. 2015 Nov;40(6):507-514.
Progesterone Enhanced Remyelination in the Mouse Corpus Callosum after Cuprizone
Induced Demyelination.
Kashani IR PhD(1), Hedayatpour A PhD(1), Pasbakhsh P PhD(1), Kafami L PhD(2),
Khallaghi B MSc(3), Malek F MSc(1).
(1)Department of Anatomical Sciences, School of Medicine, Tehran University of
Medical Sciences, Tehran, Iran. (2)Department of Pathobiology, School of
Medicine, Alborz University of Medical Sciences, Karaj, Iran ; Shefa
Neurosciences Research Center, Tehran, Iran. (3)Shefa Neurosciences Research
Center, Tehran, Iran.
BACKGROUND: Progesterone as a sex steroid hormone is thought to affect and
prevent demyelination, but its role in promoting myelin repair is far less
investigated. In this study, remyelinating potential of progesterone in corpus
callosum was evaluated on an experimental model of MS.
METHODS: In this experimental study, adult male C57BL/6 mice were fed with 0.2%
(w/w) cuprizone in ground breeder chow ad libitum for 6 weeks. At day zero, after
cuprizone removal, mice were divided randomly into two groups: (a) placebo group,
which received saline pellet implant, (b) progesterone group, which received
progesterone pellet implant. Some mice of the same age were fed with their normal
diet to serve as the healthy control group. Two weeks after progesterone
administration, Myelin content was assessed by Luxol-fast blue staining. The
myelin basic protein (MBP) and proteolipid protein (PLP) expression were assessed
using Western blot analysis and the changes in the number of oligodendrocytes and
oligodendroglial progenitor cells were assessed by immunohistochemistry (IHC) and
flow cytometry.
RESULTS: Luxol-fast blue staining revealed enhanced remyelination in the
progesterone group when compared with the placebo group. Densitometry
measurements of immunoblots demonstrated that MBP and PLP proteins contents were
significantly increased in the progesterone group compared with the placebo
group. Flow cytometry and IHC analysis showed increases in Olig2 and O4 cells in
the progesterone group compared with the placebo group.
CONCLUSION: Overall, our results indicate that progesterone treatment can
stimulate myelin production and that it may provide a feasible and practical way
for remyelination in diseases such as multiple sclerosis.
2. Pak J Pharm Sci. 2015 Jul;28(4 Suppl):1563-6.
Review: Effect study of sex hormone in the multiple sclerosis of common
neurological disorders.
Xin Y(1), Xu D, Yang X(1), Liu A(1), Zhou X, Guo B(1).
(1)Maternal and Child Health Hospital of Zhengzhou City, Zhengzhou City, Henan
Province, PR China.
Multiple sclerosis (MS) is one of most common neurological disorders, mainly
affecting women. The central nervous system (CNS) of this autoimmune disease is
characterized by intermittent or chronic damage to the myelin sheaths
(demyelination), local inflammation and axonal degeneration. During the early
relapsing/remitting stages of MS, myelin can regenerate. However, as the disease
progresses, both amount and activity of regenerated axons becomes insufficient,
leading to impaired axon conduction, neurodegeneration and the worsening
symptoms. Epidemiological study found that distinct symptom alleviation of
diseases at a certain periods would be shown in women during pregnancy. The
following basic researches indicated that sex hormones especially progesterone
can significantly reduce the disease severity, moreover, the protective effect of
sex hormone on the nervous system has become the research focus.
Acta Neurol Scand Suppl. 2015;132(199):62-70.
Hormonal and gender-related immune changes in multiple sclerosis.
Airas L(1).
(1)Division of Clinical Neurosciences, Turku University Hospital, Turku, Finland.
Similarly to many other autoimmune diseases, multiple sclerosis (MS) is more
common among women than men, and its incidence among women is rising. There are
also qualitative differences in the disease course between men and women, with
male patients experiencing increased disease progression, brain atrophy, and
cognitive impairment. During pregnancy, women with MS typically have a greatly
reduced relapse rate, whereas very soon after the delivery, the disease activity
returns, often even at a higher level than seen in the prepregnancy year. The
reasons for the increased postpartum activity are not entirely clear, but factors
such as the abrupt decrease in estrogen levels immediately after the delivery and
the loss of the immunosuppressive state of pregnancy are likely of importance.
There is compelling evidence that estrogen, progesterone, and testosterone
control MS pathology by influencing immune responses and by contributing to
repair mechanisms in the nervous system. Hormones may thus offer important
insights into MS disease prevention and treatment. In this review, the possible
reasons for the sex bias in autoimmune diseases will be discussed. The
pregnancy-related alterations in MS, including the effect of pregnancy on disease
activity, long-term disability accumulation, and prevalence will be reviewed, as
well as the hormonal and immunological mechanisms potentially underlying these
changes. Finally, the present thinking on the effect of hormones on the changing
incidence of MS will be elucidated.
1. EMBO Mol Med. 2013 Jun;5(6):891-903. doi: 10.1002/emmm.201202124. Epub 2013 May 17.
A TSPO ligand is protective in a mouse model of multiple sclerosis.
Daugherty DJ, Selvaraj V, Chechneva OV, Liu XB, Pleasure DE, Deng W.
Department of Biochemistry and Molecular Medicine, School of Medicine, University
of California, Davis, CA, USA.
Local production of neurosteroids such as progesterone and allopregnanolone
confers neuroprotection in central nervous system (CNS) inflammatory diseases.
The mitochondrial translocator protein (TSPO) performs a rate-limiting step in
the conversion of cholesterol to pregnenolone and its steroid derivatives.
Previous studies have shown that TSPO is upregulated in microglia and astroglia
during neural inflammation, and radiolabelled TSPO ligands such as PK11195 have
been used to image and localize injury in the CNS. Recent studies have shown that
modulating TSPO activity with pharmacological ligands such as etifoxine can
initiate the production of neurosteroids locally in the injured CNS. In this
study, we examined the effects of etifoxine, a clinically available anxiolytic
drug, in the development and progression of mouse experimental autoimmune
encephalomyelitis (EAE), an experimental model for multiple sclerosis (MS). Our
results showed that etifoxine attenuated EAE severity when administered before
the development of clinical signs and also improved symptomatic recovery when
administered at the peak of the disease. In both cases, recovery was correlated
with diminished inflammatory pathology in the lumbar spinal cord. Modulation of
TSPO activity by etifoxine led to less peripheral immune cell infiltration of the
spinal cord, and increased oligodendroglial regeneration after inflammatory
demyelination in EAE. Our results suggest that a TSPO ligand, e.g. etifoxine,
could be a potential new therapeutic option for MS with benefits that could be
comparable to the administration of systemic steroids but potentially avoiding
the detrimental side effects of long-term direct use of steroids.
Copyright © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of
EMBO.
2. J Neurochem. 2010 Aug;114(3):921-32.
Sex-dimorphic changes in neuroactive steroid levels after chronic experimental
autoimmune encephalomyelitis.
Caruso D, D'Intino G, Giatti S, Maschi O, Pesaresi M, Calabrese D, Garcia-Segura
LM, Calza L, Melcangi RC.
Department of Pharmacological Sciences, Università degli Studi di Milano, Milano,
Italy.
Our previous observations have shown that neuroactive steroid levels in the brain
are affected by acute experimental autoimmune encephalomyelitis (EAE) with sex
and regional specificity (Giatti et al. 2010). To better understand the effect of
EAE on neuroactive steroids, we have here assessed the levels of pregnenolone,
progesterone and its derivatives (i.e. dihydroprogesterone,
tetrahydroprogesterone and isopregnanolone), testosterone and its derivatives
(dihydrotestosterone and 5alpha-androstane-3alpha, 17beta-diol) in different CNS
regions of male and female rats affected by chronic EAE. Data obtained by liquid
chromatography tandem mass spectrometry revealed that chronic EAE results in sex
and regional specific alterations in the levels of neuroactive steroids in the
brain, which are in many cases different to those produced by acute EAE. The
specific changes in neuroactive steroid levels after chronic EAE may be of
relevance to design new possible therapeutic strategies for the disease.
3. Maturitas. 2003 Dec 10;46 Suppl 1:S71-5.
Differential effects of progestins on the brain.
Gruber CJ, Huber JC.
Department of Gynecological Endocrinology and Reproductive Medicine, University
of Vienna Medical School, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
[email protected]
Interactions exist between progestins and the gamma-aminobutyric acid (GABA)
receptor subtype A where C(21)-steroids function as activators. Other
interactions between progesterone and neurotransmitter systems include
stimulation of dopamine release in striatal tissue, stimulation of GnRH release
from hypothalamic neurons and inhibition of opioid receptor binding and
activation. Cyproterone acetate increases dopaminergic responses and binds to
opiate receptors independently of its classical effect on the androgen receptor.
Progesterone substitution in perimenopausal women promotes length and quality of
sleep. This effect seems most prominent for progesterone administered vaginally.
Progestins also play a role in the pathogenesis of migraine. Migraine symptoms
occur predominantly during the perimenstrual stage. Women who suffer from
menstrual migraine triggered by premenstrual progesterone loss often benefit from
cyclic progesterone administration. This may be because progesterone and
allopregnenolone reduce meningeal release of substance P and inhibit the
development of neurogenic oedema. Women whose migraine symptoms subside during
pregnancy, however, benefit from intramuscular medroxyprogesterone acetate.
Progesterone, generated from pregnenolone by Schwann cells, also enhances myelin
synthesis. Myelination of axons is promoted when progesterone is added to
cultures of rat dorsal root ganglia. No reliable data exist with respect to the
effects of other progestins on demyelinating disease. Progestins promote the
growth of meningioma as progesterone receptors predominate in meningioma tissue.
Progesterone and synthetic progestins should therefore not be prescribed in these
patients.
[Topical DHT]
It’s effective topically, but it might take several milligrams on the skin to absorb one mg.
[MS-like symptoms... including numbness in some finger tips, loss of dexterity in those same fingers, depression.]
Have you tried pregnenolone? DHT is probably safe, since it can’t turn into estrogen.
[DHEA turning to estrogen when taking a few mg]
I don’t think that’s a risk with 5 mg or less. Things that protect against aromatase include aspirin, thyroid, vitamin D, pregnenolone, and sugar.
[Thanks. Is there anything else I should try for sudden onset of possible MS-like symptoms (numbness in hands, clumsiness, mild visual distortion, memory problems)? I take thyroid, aspirin, pregnenolone, vitamin A. I just started taking more vitamin D, and using the chicken lights more.]
That list of symptoms reminds me of the first woman I knew who used progesterone for MS. She recovered completely, and gave a good lecture to my endocrinology class at the NCNM naturopathic school.
Iran J Med Sci. 2015 Nov;40(6):507-514.
Progesterone Enhanced Remyelination in the Mouse Corpus Callosum after Cuprizone
Induced Demyelination.
Kashani IR PhD(1), Hedayatpour A PhD(1), Pasbakhsh P PhD(1), Kafami L PhD(2),
Khallaghi B MSc(3), Malek F MSc(1).
(1)Department of Anatomical Sciences, School of Medicine, Tehran University of
Medical Sciences, Tehran, Iran. (2)Department of Pathobiology, School of
Medicine, Alborz University of Medical Sciences, Karaj, Iran ; Shefa
Neurosciences Research Center, Tehran, Iran. (3)Shefa Neurosciences Research
Center, Tehran, Iran.
BACKGROUND: Progesterone as a sex steroid hormone is thought to affect and
prevent demyelination, but its role in promoting myelin repair is far less
investigated. In this study, remyelinating potential of progesterone in corpus
callosum was evaluated on an experimental model of MS.
METHODS: In this experimental study, adult male C57BL/6 mice were fed with 0.2%
(w/w) cuprizone in ground breeder chow ad libitum for 6 weeks. At day zero, after
cuprizone removal, mice were divided randomly into two groups: (a) placebo group,
which received saline pellet implant, (b) progesterone group, which received
progesterone pellet implant. Some mice of the same age were fed with their normal
diet to serve as the healthy control group. Two weeks after progesterone
administration, Myelin content was assessed by Luxol-fast blue staining. The
myelin basic protein (MBP) and proteolipid protein (PLP) expression were assessed
using Western blot analysis and the changes in the number of oligodendrocytes and
oligodendroglial progenitor cells were assessed by immunohistochemistry (IHC) and
flow cytometry.
RESULTS: Luxol-fast blue staining revealed enhanced remyelination in the
progesterone group when compared with the placebo group. Densitometry
measurements of immunoblots demonstrated that MBP and PLP proteins contents were
significantly increased in the progesterone group compared with the placebo
group. Flow cytometry and IHC analysis showed increases in Olig2 and O4 cells in
the progesterone group compared with the placebo group.
CONCLUSION: Overall, our results indicate that progesterone treatment can
stimulate myelin production and that it may provide a feasible and practical way
for remyelination in diseases such as multiple sclerosis.
2. Pak J Pharm Sci. 2015 Jul;28(4 Suppl):1563-6.
Review: Effect study of sex hormone in the multiple sclerosis of common
neurological disorders.
Xin Y(1), Xu D, Yang X(1), Liu A(1), Zhou X, Guo B(1).
(1)Maternal and Child Health Hospital of Zhengzhou City, Zhengzhou City, Henan
Province, PR China.
Multiple sclerosis (MS) is one of most common neurological disorders, mainly
affecting women. The central nervous system (CNS) of this autoimmune disease is
characterized by intermittent or chronic damage to the myelin sheaths
(demyelination), local inflammation and axonal degeneration. During the early
relapsing/remitting stages of MS, myelin can regenerate. However, as the disease
progresses, both amount and activity of regenerated axons becomes insufficient,
leading to impaired axon conduction, neurodegeneration and the worsening
symptoms. Epidemiological study found that distinct symptom alleviation of
diseases at a certain periods would be shown in women during pregnancy. The
following basic researches indicated that sex hormones especially progesterone
can significantly reduce the disease severity, moreover, the protective effect of
sex hormone on the nervous system has become the research focus.
Acta Neurol Scand Suppl. 2015;132(199):62-70.
Hormonal and gender-related immune changes in multiple sclerosis.
Airas L(1).
(1)Division of Clinical Neurosciences, Turku University Hospital, Turku, Finland.
Similarly to many other autoimmune diseases, multiple sclerosis (MS) is more
common among women than men, and its incidence among women is rising. There are
also qualitative differences in the disease course between men and women, with
male patients experiencing increased disease progression, brain atrophy, and
cognitive impairment. During pregnancy, women with MS typically have a greatly
reduced relapse rate, whereas very soon after the delivery, the disease activity
returns, often even at a higher level than seen in the prepregnancy year. The
reasons for the increased postpartum activity are not entirely clear, but factors
such as the abrupt decrease in estrogen levels immediately after the delivery and
the loss of the immunosuppressive state of pregnancy are likely of importance.
There is compelling evidence that estrogen, progesterone, and testosterone
control MS pathology by influencing immune responses and by contributing to
repair mechanisms in the nervous system. Hormones may thus offer important
insights into MS disease prevention and treatment. In this review, the possible
reasons for the sex bias in autoimmune diseases will be discussed. The
pregnancy-related alterations in MS, including the effect of pregnancy on disease
activity, long-term disability accumulation, and prevalence will be reviewed, as
well as the hormonal and immunological mechanisms potentially underlying these
changes. Finally, the present thinking on the effect of hormones on the changing
incidence of MS will be elucidated.
1. EMBO Mol Med. 2013 Jun;5(6):891-903. doi: 10.1002/emmm.201202124. Epub 2013 May 17.
A TSPO ligand is protective in a mouse model of multiple sclerosis.
Daugherty DJ, Selvaraj V, Chechneva OV, Liu XB, Pleasure DE, Deng W.
Department of Biochemistry and Molecular Medicine, School of Medicine, University
of California, Davis, CA, USA.
Local production of neurosteroids such as progesterone and allopregnanolone
confers neuroprotection in central nervous system (CNS) inflammatory diseases.
The mitochondrial translocator protein (TSPO) performs a rate-limiting step in
the conversion of cholesterol to pregnenolone and its steroid derivatives.
Previous studies have shown that TSPO is upregulated in microglia and astroglia
during neural inflammation, and radiolabelled TSPO ligands such as PK11195 have
been used to image and localize injury in the CNS. Recent studies have shown that
modulating TSPO activity with pharmacological ligands such as etifoxine can
initiate the production of neurosteroids locally in the injured CNS. In this
study, we examined the effects of etifoxine, a clinically available anxiolytic
drug, in the development and progression of mouse experimental autoimmune
encephalomyelitis (EAE), an experimental model for multiple sclerosis (MS). Our
results showed that etifoxine attenuated EAE severity when administered before
the development of clinical signs and also improved symptomatic recovery when
administered at the peak of the disease. In both cases, recovery was correlated
with diminished inflammatory pathology in the lumbar spinal cord. Modulation of
TSPO activity by etifoxine led to less peripheral immune cell infiltration of the
spinal cord, and increased oligodendroglial regeneration after inflammatory
demyelination in EAE. Our results suggest that a TSPO ligand, e.g. etifoxine,
could be a potential new therapeutic option for MS with benefits that could be
comparable to the administration of systemic steroids but potentially avoiding
the detrimental side effects of long-term direct use of steroids.
Copyright © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of
EMBO.
2. J Neurochem. 2010 Aug;114(3):921-32.
Sex-dimorphic changes in neuroactive steroid levels after chronic experimental
autoimmune encephalomyelitis.
Caruso D, D'Intino G, Giatti S, Maschi O, Pesaresi M, Calabrese D, Garcia-Segura
LM, Calza L, Melcangi RC.
Department of Pharmacological Sciences, Università degli Studi di Milano, Milano,
Italy.
Our previous observations have shown that neuroactive steroid levels in the brain
are affected by acute experimental autoimmune encephalomyelitis (EAE) with sex
and regional specificity (Giatti et al. 2010). To better understand the effect of
EAE on neuroactive steroids, we have here assessed the levels of pregnenolone,
progesterone and its derivatives (i.e. dihydroprogesterone,
tetrahydroprogesterone and isopregnanolone), testosterone and its derivatives
(dihydrotestosterone and 5alpha-androstane-3alpha, 17beta-diol) in different CNS
regions of male and female rats affected by chronic EAE. Data obtained by liquid
chromatography tandem mass spectrometry revealed that chronic EAE results in sex
and regional specific alterations in the levels of neuroactive steroids in the
brain, which are in many cases different to those produced by acute EAE. The
specific changes in neuroactive steroid levels after chronic EAE may be of
relevance to design new possible therapeutic strategies for the disease.
3. Maturitas. 2003 Dec 10;46 Suppl 1:S71-5.
Differential effects of progestins on the brain.
Gruber CJ, Huber JC.
Department of Gynecological Endocrinology and Reproductive Medicine, University
of Vienna Medical School, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
[email protected]
Interactions exist between progestins and the gamma-aminobutyric acid (GABA)
receptor subtype A where C(21)-steroids function as activators. Other
interactions between progesterone and neurotransmitter systems include
stimulation of dopamine release in striatal tissue, stimulation of GnRH release
from hypothalamic neurons and inhibition of opioid receptor binding and
activation. Cyproterone acetate increases dopaminergic responses and binds to
opiate receptors independently of its classical effect on the androgen receptor.
Progesterone substitution in perimenopausal women promotes length and quality of
sleep. This effect seems most prominent for progesterone administered vaginally.
Progestins also play a role in the pathogenesis of migraine. Migraine symptoms
occur predominantly during the perimenstrual stage. Women who suffer from
menstrual migraine triggered by premenstrual progesterone loss often benefit from
cyclic progesterone administration. This may be because progesterone and
allopregnenolone reduce meningeal release of substance P and inhibit the
development of neurogenic oedema. Women whose migraine symptoms subside during
pregnancy, however, benefit from intramuscular medroxyprogesterone acetate.
Progesterone, generated from pregnenolone by Schwann cells, also enhances myelin
synthesis. Myelination of axons is promoted when progesterone is added to
cultures of rat dorsal root ganglia. No reliable data exist with respect to the
effects of other progestins on demyelinating disease. Progestins promote the
growth of meningioma as progesterone receptors predominate in meningioma tissue.
Progesterone and synthetic progestins should therefore not be prescribed in these
patients.