Bioidentical Hormones 101 
The Book, by Jeffrey Dach MD

Chapter 13. BioIdentical Hormones Relieve Anxiety

Chapter 13.  BioIdentical Hormones Relieve Anxiety

56 year old Susan suffered from anxiety and panic attacks, and had been prescribed Valium™, Effexor™ and Wellbutrin™ by her primary care doctor.  This cocktail of psychoactive drugs caused Susan adverse side effects, and didn't seem to be helping, so she stopped taking them.  A few years ago, after she went through menopause, she started having hot flashes, and this is when she first noticed the anxiety attacks, preceding the hot flashes.

Estrogen Deficiency Causes Anxiety

We sent Susan to the lab for a hormone panel, and sure enough, Susan's estrogen level was low. Susan's symptoms were caused by menopausal estrogen deficiency, a finding commonly seen in the post menopausal age group. Symptoms are promptly relieved with bioidentical estradiol applied as a topical cream twice a day.  Additionally, Susan's tests revealed vitamin and mineral deficiencies which were, no doubt, aggravating the anxiety attacks.  Susan was started on her bioidentical hormone program which included estradiol and progesterone as a balanced topical cream. She was also started on vitamin B12 and magnesium supplements.  Six weeks later, Susan reported that her anxiety and panic attacks had improved and were almost gone.  She also noticed better sleep and more clarity of mind, and her night sweats and hot flashes had resolved as well.

Anxiety is Associated with Hot Flashes

A study published in 2005 Menopause reported that anxiety is strongly associated with menopausal hot flashes, and usually precedes the hot flash episode. (13)  Hot flashes are caused by estrogen deficiency, and are treated with bioidentical estradiol, which virtually eliminates them.(15)(16)(17)

The Benefits of Bioidentical Estrogen

Previous chapters have discussed the safety and the importance of bioidentical hormones.  Uzzi Reiss's book, “Natural SuperWoman”, contains an excellent discussion of bioidentical hormones.  Chapter 4 covers anxiety, panic attacks and relief with bioidentical estrogen.(1)  Numerous articles (see below) summarize the medical literature showing that low estrogen levels cause anxiety and depression in humans and animals.  Estrogen treatment relieves anxiety and depression as well as virtually eliminates the hot flashes.

Important Point:

Hot Flashes, anxiety and panic attacks are estrogen deficiency symptoms, relieved with bioidentical estrogen.  SSRI anti-depressants do not contain estrogen, and their use for estrogen deficiency is an abuse and victimization of women who suffer from estrogen deficiency.  SSRI drugs should not be used to treat estrogen deficiency symptoms.


What is the Mechanism of Action of Estrogen in Eliminating Anxiety and Depression?

Estrogen receptors have been found in the brain, and estrogen increases the expression of an enzyme in the brain called tryptophan hydroxylase-2 (TPH2).  This enzyme’s job is to convert tryptophan to serotonin, an important neurotransmitter responsible for anti-anxiety and calming effect in the brain.  These estrogen receptors have been isolated to specific areas of the brain called the DRN, or the Dorsal Raphe Nuclei (2-6).

Estrogen Effective for Perimenopausal Depression

A study published in the 2001 Archives of General Psychiatry evaluated bioidentical estrogen as treatment for peri-menopausal depression.  They evaluated fifty women ages 40-55 years, suffering from a depressive disorder and irregular menstrual periods.  These women were treated with bioidentical estrogen or placebo over 12 weeks.  Remission of depression was observed in 17 (68%) women treated with bioidentical estradiol compared with only 5 (20%) in the placebo group.  The authors concluded,  "Transdermal estradiol is an effective treatment of depression for perimenopausal women."(7)

Estrogen Effective for Post-Partum Depression (after child birth)

Postpartum depression is seen in approximately 13% of women who have recently given birth, and often remains untreated. (10)  Various treatments have been tried, including antidepressant drug therapy (SSRI's), bioidentical estrogen, individual psychotherapy, and group psychotherapy. (10)

A study published in the 2001 Journal of Clinical Psychiatry showed that bioidentical estrogen is effective for post-partum depression.(8) Twenty-three women suffering from postpartum depression were recruited from a psychiatric emergency unit.  The women were treated over 8 weeks with bioidentical estradiol (sublingual form).  Baseline serum estradiol levels were very low suggesting ovarian failure. During the first week of estradiol treatment, depressive symptoms resolved rapidly, and serum estradiol levels increased considerably.  By the second week of treatment, 83% of patients showed clinical recovery.

A second earlier study published in 1996 Lancet showed that bioidentical estrogen is an effective treatment for post-partum depression.  Sixty One women suffering from post partum depression were given transdermal estradiol (0.2 mg daily), and rapid improvement was reported during the first month of treatment.(9)

Many women with post-partum depression are treated with SSRI antidepressants which does not address the underlying estrogen deficiency and ovarian failure.  In my opinion, bioidentical hormone treatment is more effective and safer than SSRI antidepressants or other psychoactive drugs, and should be the preferred choice.   Bioidentical estrogen has none of the adverse effects associated with SSRI antidepressants which, after all, may end up in mother's milk, and may have adverse effects on the breast feeding baby.

Estradiol for Post Partum Psychosis

While post partum estrogen deficiency causes depression in 13%  of patients, a smaller subset go on to develop full blown post partum psychosis. Bioidentical estrogen is also effective for this more severely affected group.  A study done in Finland published in the 2001 Journal of Clinical Psychiatry evaluated 10 women suffering from post partum psychosis.  All had low serum estradiol (mean of 50 pg/ml) indicating gonadal failure.  All were treated with bioidentical estradiol, with serum estradiol levels rising to normal.  Remarkably, estradiol treatment reversed psychiatric symptoms in all patients. (11)

Estradiol  Improves Cognition for Alzheimer's Dementia

In a study published in 2001 Neurology, twenty postmenopausal women with Alzheimer's dementia were treated with bioidentical estradiol (0.10 mg per day, topical) and compared to placebo.  Sophisticated neuropsychological tests showed improvement in attention, and in verbal, visual and semantic memory compared with subjects who received a placebo.(12)

Estradiol Reduces Anxiety in Mouse Model

Alicia A. Walf examined a mouse model in which Estradiol, a bioidentical estrogen, reduces anxiety- and depression-like behavior of aged female mice.  Her findings were published in   Neuroscience Research in Feb 2010. (14)  Matthew N. Hill investigated the mechanism of estradiol as an anxiolytic, and he implicated the enzyme, fatty acid amide hydrolase (FAAH), which degrades the endocannabinoid anandamide.  The enzyme, FAAH, is regulated by estrogen.(25)  This reveals a biochemical mechanism for how estrogen relieves anxiety.   Obviously, this is a fertile area for new research, as the exact mechanism has not yet been elucidated.

For references and links, see my web site: www.bioidenticalhormones101.com

References for 12. BioIdentical Hormones Relieve Anxiety

(1)
http://www.uzzireissmd.com/refs/04.html The Natural SuperWoman, by Uzzi Reiss MD and Yfat Reiss Gendell, Avery Trade , 2008. web site page containing references for the Estrogen chapter.

(2)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2667128 Neuroscience. 2009 January 23; 158(2): 456–464.  Estrogen decreases 5-HT1B autoreceptor mRNA in selective subregion of rat dorsal raphe nucleus: inverse association between gene expression and anxiety behavior in the open field. by Ryoko Hiroiab and John F. Neumaierb

(3)
http://endo.endojournals.org/cgi/content/full/endo;146/2/797
Endocrinology Vol. 146, No. 2 797-807, 2005 by The Endocrine Society . Novel Actions of Estrogen Receptor-ß on Anxiety-Related Behaviors by Trent D. Lund, Tomislav Rovis, Wilson C. J. Chung and Robert J. Handa
(4)
http://www.ncbi.nlm.nih.gov/pubmed/15820717?dopt=Abstract
Biol Psychiatry. 2005 Apr 15;57(8):938-42. Estrogen receptor-beta regulates tryptophan hydroxylase-1 expression in the murine midbrain raphe. Gundlah C et al.

(5) http://www.ncbi.nlm.nih.gov/pubmed/19559077 Neuroscience. 2009 Oct 6;163(2):705-18. Epub 2009 Jun 23. Estrogen receptor beta regulates the expression of tryptophan-hydroxylase 2 mRNA within serotonergic neurons of the rat dorsal raphe nuclei. Donner N, Handa RJ.

(6) http://www.albany.edu/~cafrye/papers/walfFrye06review.pdf
Neuropsychopharmacology (2006) 31, 1097–1111,  2006 Nature  Perspective - A Review and Update of Mechanisms of Estrogen in the Hippocampus and Amygdala for Anxiety and Depression Behavior by Alicia A Walf and Cheryl A Frye

(7)
http://www.ncbi.nlm.nih.gov/pubmed/11386980 Arch Gen Psychiatry. 2001 Jun;58(6):529-34.  Efficacy of estradiol for the treatment of depressive disorders in perimenopausal women: a double-blind, randomized, placebo-controlled trial. by Soares CN et al.

(8) http://www.ncbi.nlm.nih.gov/pubmed/11411813 J Clin Psychiatry. 2001 May;62(5):332-6. Estrogen deficiency in severe postpartum depression: successful treatment with sublingual physiologic 17beta-estradiol: a preliminary study.by Ahokas A ET AL.

(9) http://www.ncbi.nlm.nih.gov/pubmed/8598756 Lancet. 1996 Apr 6;347(9006):930-3. Transdermal oestrogen for treatment of severe postnatal depression. by Gregoire AJ ET AL.

(10) http://www.jabfm.com/cgi/reprint/16/5/372.pdf The Effectiveness of Various Postpartum Depression Treatments and the Impact of Antidepressant Drugs on Nursing Infants Dwenda Gjerdingen, MD, MS (J Am Board Fam Pract 2003;16:372– 82.)

(11)
http://www.ncbi.nlm.nih.gov/pubmed/10817099  J Clin Psychiatry. 2000 Mar;61(3):166-9. Positive treatment effect of estradiol in postpartum psychosis: a pilot study. Ahokas A et al.

(12) http://www.neurology.org/cgi/content/abstract/57/4/605
Neurology 2001;57:605-612, 2001 American Academy of Neurology  High-dose estradiol improves cognition for women with AD Results of a randomized study by S. Asthana, MD et al.

(13) http://www.ncbi.nlm.nih.gov/pubmed/15879914 Menopause. 2005 May-Jun;12(3):258-66. The role of anxiety and hormonal changes in menopausal hot flashes. Freeman EW ET AL.

(14) http://www.ncbi.nlm.nih.gov/pubmed/19804793 Estradiol reduces anxiety- and depression-like behavior of aged female mice by Alicia A. Walf and Cheryl A. Frye  Neuroscience Research, The University at Albany-SUNY, United States September 2009

(15)
http://www.ncbi.nlm.nih.gov/pubmed/15474758  Maturitas. 2004 Oct 15;49(2):140-7. A short study in the treatment of hot flashes with buccal administration of 17-beta estradiol. Gass MS, Rebar RW, Cuffie-Jackson C, Cedars MI, Lobo RA, Shoupe D, Judd HL, Buyalos RP, Clisham PR.

(16) http://www.ncbi.nlm.nih.gov/pubmed/11400216 Menopause as a Measure of Population Health - Physiology of hot flashes Robert R. Freedman 1 2  Am. J. Hum. Biol. 13:453-464, 2001

(17) http://jcem.endojournals.org/cgi/content/abstract/61/4/627
Journal of Clinical Endocrinology & Metabolism Vol. 61, No. 4 627-632

(18)   http://jcem.endojournals.org/cgi/content/full/82/2/703   Cizza G, Gold PW, Chrousos GP. High-dose transdermal estrogen, corticotropin-releasing hormone, and postnatal depression [letter]. J Clin Endocrinol Metab 1997;82:704.

(19)
http://www.ncbi.nlm.nih.gov/pubmed/11411813 Ahokas A, Kaukoranta J, Wahlbeck K, Aito M. Estrogen deficiency in severe postpartum depression: successful treatment with sublingual physiologic 17B-estradiol: a preliminary study. J Clin Psychiatry 2001;62:332– 6.

(20)
http://www.ncbi.nlm.nih.gov/pubmed/9439497 Ahokas AJ, Turtiainen S, Aito M. Sublingual oestrogen treatment of postnatal depression [letter]. Lancet 1998;351:109.

(21)
http://www.ncbi.nlm.nih.gov/pubmed/8598756  Gregoire AJ, Kumar R, Everitt B, Henderson AF, Studd JW. Transdermal oestrogen for treatment of severe postnatal depression. Lancet 1996; 347:930–3.

(22)
http://www.ncbi.nlm.nih.gov/pubmed/10591876 Ahokas A, Aito M. Role of estradiol in puerperal psychosis. Psychopharmacology (Berl) 1999;147: 108–10.

(23)
http://www.ncbi.nlm.nih.gov/pubmed/10706019 Ahokas A, Aito M, Turiainen S. Association between oestradiol and puerperal psychosis. Acta Psychiatr Scand 2000;101:167–70.

(24)
http://www.ncbi.nlm.nih.gov/pubmed/11317610  Granger ACP, Underwood MR. Review of the role of progesterone in the management of postnatal mood disorders. J Psychosom Obstet Gynaecol 2001;22:49 –55.

(25) http://science.iowamedicalmarijuana.org/pdfs/psych/Hill%202007.pdf  Estrogen recruits the endocannabinoid system to modulate emotionality. Matthew N. Hill, Eda S. Karacabeyli, Boris B. Gorzalka.Psychoneuroendocrinology (2007) 32, 350–357
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