Menopause Related Depression

Up to 29% of Menopousal women will experience depression during the menopausal change.   The erratic hormone fluctuations during this transition can cause depressive symptoms (1;2;3). In the female brain estrogen is a neuromodulator, meaning it can change or disrupt the production of neurotransmitters, including those involving mood.  In most women, until the onset of pre-menopause, the brain is able to deal with changes brought on by fluctuating hormones during the menstrual cycle.  At the onset of pre-menopause some women (with a history of depression, premenstrual depression, or postpartum depression/baby blues, or those with a genetic vulnerability to depression) may be vulnerable to hormone related depression (1).   The symptoms of which are: tiredness, sadness, irritability, disinterest in things, sleeping too much or too little, eating too much or too little, and even anger.  These symptoms are due in part to wild shifts in sex hormones, which then effect neurotransmitter production (1;2;3).

For the 18% to 29% of women experienceing hormonally related menopausal depression (1), the “inability to rapidly establish a new baseline of neuronal function could lead to increased susceptibility to mood disorders and diminished brain-related functions” (1, p.5). In other words, their ability to think clearly may be altered and their mood may become depressed or erratic.

This phenomenon is rooted in part in the adrenal glands role in producing hormones, including sex hormones. In the female body it produces sex hormones (4) (up to 50% after menopause) and stress related hormones, like cortisol and adrenaline.  If the adrenals are producing stress hormones, they are less likely to be able to make sex hormones at the same time (5).  Ironically, in this situation stress and depression act like a feedback loop, making it harder for women to regulate ovarian hormones, which can lead to early onset menopause (1).  To make matters worse, if a woman’s body is under prolonged stress, her body will convert progesterone (a sex hormone) into cortisol (a stress hormone).  Cortisol then disrupts the brains production f something called BDNF (Brain-derived neurotrophic factor) which is associated with keeping the brain healthy (helping make new neurons and connections between existing neurons).  Low levels of BDNF have been connected to depression (53).  If a person stops making enough BDNF to keep their brain healthy for a long enough time, parts of the brain will start to atrophy or shrink (6).

How to deal with these problem:

Sleep hygiene is important.  Having a routine helps maintain dopamine levels (56).

Manage stress, high stress levels are connected to low dopamine levels (56).

Exercise is important to psychological well-being as  increases the production of neurotransmitters (Dopamine, Norepinephrine and Serotonin) that are necessary for healthy brain functioning and emotional well-being (32).  It also increases blood circulation in the brain, which positively impacts hormones and increases dopamine levels (56).  Exercise forces the brain to make BDNF (7). It is also linked to improved mood and feeling fewer physical symptoms of menopause (34;35). In fact, menopausal women who exercise have been shown to assess their symptoms as being less important and so cope better with them (36).  Do yoga, it helps make the neurotransmitter GABA (gamma-aminobutric acid) which lessens anxiety and helps keep you calm.  Yoga practice helps individuals learn to control negative emotions like anger, anxiety, and depression, (37). It may be better than cognitive behavioral therapy for stress management, anxiety, and depression (38).    Exercise helps make the hormone DHEA (Dehydroepiandrosterone) (41), which helps depression (39) self esteem and low energy (40).  DHEA can improve immune response (41) and memory (42).  Exercise four times a week to improve GABA.  Get enough sleep, as this helps balance hormones and neurotransmitters (52).

Dietarily:

To increase GABA eat the following foods high in glutamic acid: oats, whole wheat, whole grains, almonds or tree nuts, oranges and other citrus fruits, bananas, beef liver, halibut, lentils, broccoli, brown rice, rice bran, potato’s (52).

For BDNF production eat oily fish, blue berries, red grapes, and dark chocolate (12;13).

For DHEA eat good fats with plenty of omega 3 fatty acids.  Eat pumpkin seeds, raw butter, ghee, and the following oils: flax, palm, olive and cod liver (43).

For serotonin eat the following foods: turmeric, dark chocolate, green tea, cold-water fatty fish, and fermented foods (yogurt, kefir, unpasteurized sauerkraut).  The last helps balance gut bacteria as too much of a bacterium called lipopolysaccharides can lower serotonin levels (22;26;27).  Also, eat Tryptophan (an amino acid) rich foods.   Eat complex carbohydrates, these make more serotonin than protein based foods with Tryptophan.  Protein has been found to block the production of serotonin so, eat sweet or starchy (ideally complex) carbohydrates without protein (22;23; 24).  Eat low or fat free, and protein free, carbohydrates on an empty stomach (about three hours after a protein).  The food source (like gram crackers, pretzels etc.,) should have at least 25 to 35 grams of carbohydrates and no more than 4 grams of protein.  Try to eat less than three grams of fat per serving as this can increase your weight.  If you want a quick boost to your mood try a simple carbohydrate, but keep in mind that this will raise your blood sugar levels.  You should feel an effect 20 to 40 minutes after eating (25).

For dopamine eat bananas, (the riper the better), almonds, apples, watermelons, cherries, yogurt, beans, eggs, and meats (56).

Drink green and black tea to increase BDNF (12;13).

Do not eat sugar, processed foods or high fructose corn syrup, as these disrupt BDNF production (10) and dopamine production  (56).

For BDNF take these supplements: zinc, magnesium (14), and curcumin supplements, or cook with the spice turmeric (11;51) or curcumin (8). Some antidepressants do work to increase BDNF production (9).

For dopamine address any magnesium deficiencies (56). Symptoms include cravings for salt and carbohydrates, having high blood pressure, being constipated, muscle spasms or pain, head ache, feeling  tired, mood swings (anxiety or irritability) and other signs of depression, and experiencing heart palpitations or a rapid heartbeat (56).

For dopamine take vitamins C and E (56).

Take vitamin B6 to increase GABA (52).

Regarding DHEA, in Canada it is only available as a prescription (44).  Conversely, DHEA is available for sale as a supplement in the US (45).

Reduce or eliminate caffeine as it may desensitize brain cells to serotonin (46) and dopamine levels decrease after drinking coffee (56), and avoid artificial sweeteners (aspartame) as it inhibits the uptake and conversion of tryptophan (22; 47).

For depression in general adding vitamins (B6, B9 and B12), and supplements (SAM-e, that is S-adenosylmethionine) to your diet can help (28; 29). Magnesium has been found to substantially help with treatment resistant depression (82) as have vitamin D and amino acids, especially tryptophan (30).

Take the amino acids tyrosine and l-phenylalanine or phenylalanine (which the body makes into tyrosine) to make dopamine.

Chlorella, a green alga, has been shown in clinical trials to reduce the symptoms of depression and anxiety (31). Kava extract has been effective for some people as an alternative to pharmaceuticals (4).

The following have also been shown to improve mood in depressed individuals:  music therapy, and relaxation training (33).

To increase both serotonin and BDNF eat probiotics and prebiotics.  Eating probiotics (bacterial culture found in fermented foods like yogurt, kimchi, pickles and sauerkraut) or taking supplements and prebiotics help relieve depression, anxiety and thought related problems (54).  Eat lactobacillus rhamnosus (55) Lactobacillus casei Lactobacillus helveticus and Bifidobacterium longum (54). Serotonin and BDNF production is also improved by eating prebiotics (starches that nurture good bacteria) like squash, onions, sweet potatoes and asparagus can also help increase BDNF (14;15) and serotonin.

Treatment for depression: Peri-menopausal depression and premenstrual symptoms also respond to hormone replacement therapy (HT/HRT) (1). And, many women opt for estrogen replacement therapy (ERT) (16; 17), which has been shown to increase a sense of well-being (18). For some postmenopausal women, HRT combined with a type of anti-depressant/anti-anxiety drug called selective serotonin reuptake inhibitors (SSRIs) may work better than SSRIs alone (1).   Others may opt for natural remedies and biodentical hormone therapy.

In some studies light therapy (especially blue light) has recently been proven more effective than anti-depressants in treating depression (19) and combining light therapy with antidepressants was even more effective. Blue light exposure helps anxiety as well.  It increases production of serotonin and may strengthen and stimulate the areas of the brain responsible for processing emotion and language.  This in effect enables better handling of stressful situations and greater mood regulation (20).  Ideally you would get enough light naturally, by walking outside in sunlight for 15 minutes a day.  Alternatively, you can buy an inexpensive light box at most retailers, or online, or try installing full-spectrum high-quality (fluorescent) lightbulbs in your home and place of work.  Keep in mind that blue light can harm your eyes, so don’t look directly at it.  Also, avoid blue light at night as it may affect the ability to go to sleep (including TV and tablet screens).   If you purchase a blue light box place it on a high enough surface to allow the light to hit the lower part of the eye, as this is where blue spectrum light naturally is absorbed (21). Red/infrared light also increases serotonin, dopamine, and BDNF.

Other pre-and perimenopause related medical problems that cause depressive symptoms and anxiety are thyroid problems (48), deficiencies in B vitamins (especially B 6 and 12 [49]) and iron (anemia) due to excessive bleeding (50).

References:

1   Deecher, D., Andree, T.H., Sloan, D., & Schechter, L.E., (2008).  From menarche to menopause: Exploring the underlying biology of depression in women experiencing hormonal change.   Psychoneuroendocrinology, 33, 3-17.

2   Epperson, C.N., Amin, Z., Ruparel, K.L., Gur, R., & Loughead, J., (2012).  Interactive effects of      estrogen and serotonin on brain activation during working memory and affective processing in menopausal women.  Psychoneuroendocrinology, 37, 372-382.

3 Pearlstein, T.B.  (1995).  Hormones and depression: What are the facts about premenstrual syndrome, menopause, and hormone replacement therapy? American Journal of Obstetric Gynecology, 173, (92) 646-653.

4   Pittler, M.H., & Ernst, E., (2000).  Efficacy of Kava extract for treating anxiety: systematic review and meta-analysis.  Journal of Clinical Psychopharmacology, 20 (1), 84-89.  Accessed: http://journals.lww.com/psychopharmacology/Abstract/2000/02000/Efficacy_of_Kava_Extract_for_Treating_Anxiety.14.aspx

5   Women to women website, run by Dr. Marcelle Pick, OB-GYN, NP.  Webpage:  Am I in menopause.  Accessed at:  https://www.womentowomen.com/menopause-perimenopause/am-i-in-menopause-2/

6   Warner-Schmidt JL, Duman RS (2006). Hippocampal neurogenesis: opposing effects of stress and antidepressant treatment. Hippocampus. 16 (3): 239–49. doi:10.1002/hipo.20156. PMID 16425236.

7   Russo-Neustadt AA, Beard RC, Huang YM, Cotman CW (2000). Physical activity and antidepressant treatment potentiate the expression of specific brain-derived neurotrophic factor transcripts in the rat hippocampus. Neuroscience, 101 (2): 305–12. doi:10.1016/S0306-4522(00)00349-3. PMID 11074154.

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 9   Shimizu E, Hashimoto K, Okamura N, Koike K, Komatsu N, Kumakiri C, Nakazato M, Watanabe H, Shinoda N, Okada S, Iyo M (Jul 2003). Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants. Biological Psychiatry. 54 (1): 70–5. doi:10.1016/S0006-3223(03)00181-1.

10   Rendeiro, C., Vauzour, D., Rattray, M., Waffo-Teguo, P., Merillon, J.M., Butler, L.T., Williams, C.M., & Spencer, J.P., (2013).  Dietary levels of pure flavonoids improve spatial memory performance and increase hippocampal brain-derived neurotrophic factor.  Plos One 8 (5) Doi: 10.1371/journal.pone.

11 Mishra, S., & Palanivelu, K. (2008).  The effect of curcumin (tumeric) on Alzheimerès disease: An overview.  Annals of Indian                   Acandemy of Neurology, 11, (1), 13-19.

12    The Longevity plan with Dr. John Day website.  Webpage: 081 10 ways to boost brain function with BDNF.  Accessed            on: March 15th, 2017.   Accessed at: http://drjohnday.com/10-ways-to-boost-            brain-function-with-bdnf/

13    Fengj, H., & MacGregor, G.A. (2001). Beneficial effects of potassium.  The BMJ, 323, 497-501.

14   Webpage: Optimal Living Dynamics. Webpage: 21 proven ways to increase your brain’s growth hormone.   Accessed at:                       http://www.optimallivingdynamics.com/blog/21-proven-ways-to-increase-your-brains-growth-hormone

15    Savignac, H.M., Corona, G., Mills, H., Chen, L.  Spencer, J.P.E., Tzortzis, G., & Burnet, P.W.J., (2013).  Prebiotic feeding elevates central brain derived neurotrophic factor.  N-methyl-D-aspartate receptor subunits and D-serine.  Neurochemistry International 63 (8) 756-754.  Doi: 10.1016/j.neuint.2013.10006

16  Han, K.K., Soares, J.H., Haidar, M.A., deLima, G.R., & Baracat, E.C. (2002).  Benefits of soy isoflavone                                         therapeutic regiment on menopausal sysmtoms. Obstetrics & Gynocology, 99, (3)389-394.

17    Fagulha, T., Goncalves, B., & Ferreira, A. (2011).  A population-based assesment of midlife portuguese women’s experience of primenopuase and menopause.  Health Care for Women International, 32, 559-580.

18   Streeter, C.C., Whitfield, H., Owen, L., Rein, T., Karri, S.K., Yakhkind, A., Perlmutter, R., Prescot, A., Renshaw, P.F., Ciraulo, D.A., & Jensen, J.E. (2010).  Effects of yoga versus walking on mood, anxiety, and brain GABA levels:  A randomized contgrolled MRS study.  Journal of Altrnative and Complentary Medicine, 16, (11), 1145-1152.

19    Lam, R.W., Levitt, A.J., Levitan, R.D., Michalak, E.E., Cheung, A.H., Morehouse, R., Ramasubbu, R., Yatham, L.N., & Tam        , E.M., (2016).  Efficacy of bright light treatment, Fluoxetine, and the combination in patients with non-seasonal    major depressive disorder, JAMA Psychiatry, 73 (1), 56-63.

20   Mercola website.  Webpage: Blue light may be key to fighting winter blues.  Accessed:                 www.articles.mercola.com/sites/articles/archive/2010/14/blue-light-may-be-key-to-fighting-winter-            blues.aspx

21    Psych Education website.  Webpage:  Light Therapy for Depression.  www.psycheducation.org/treatment/bipolar-               dosorder-light-and-darkness/light-thrapies-for-depression.

22     Be Brain Fit website.  Webpage: Serotonin foods and mood disorders, by Alban, D. accessed at: http:    bebrainfit.com/serotonin-foods-mood-brain/

23     Sayegh, R., Schiff, I., Wurtman, J., Spiers, P., McDermott, J., & Wurtman, R., (1995).  The effect of a       carbohydrate-rich beverage on mood, appetite, and cognitive function in women with       premenstrual syndrome.  American Journal of Obstetrics & Gynecology, 86 (4, pt. 1) 520-528.

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26   Bercik, P., Denou, E., Collins, J., Jackson, W., Lu, J., Deng, Y., Blennerhassett, P., Macri, J., McCoy, K.D.,            Verdu, E.F., & Collins, S.M., (2011).  The intestinal microbiota affect central levels of brain-derived            neurotropic factor and behavior in mice.  Gastroenterology 14 (12) 599-609.  Doi:         10.1053/j.gastro.2011.04.052.

27    O’Connor, J.C., Lawson, M.A., Andre, C., Moreau, M., Lesage, J., Castanon, N., Kelley, K.W., & Dantzer, R.,       (2009). Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice.   Molecular Psychiatry 14, 511-522.

28   Volker, D., & Jade, N.G. (2006).  Depression: Does nutrition have an adjunctive treatment role?  Nutrition & Dietetics, 63, 213-226.

29   WebMD website. Webpage: Vitamins and Supplements Lifestyle Guide, SAM-e (S-adonosylmethionine, SAMe).  Retrieved from,www.webmd.com/vitamins-and- supplements/lfiestyle-guide-11/suppliment-guide-sam-e

30     Nerogestics, the brain wellness program website.  Webpage:  Amino acids. Accessed:                 https://www.neurogistics.com/TheScience/AminoAcids.asp

31    Panahi, Y., Badeli, R., Karami, G., Bandeli, Z., & Sahebkar, A., (2015).  A randomized controlled trial of 6-week Chlorella vulgaris                 supplementation in patients with major depressive disorder.  Complementary Therapies in Medicine, 23 (4), 598-602.

32   Kita, I. (2014).  Physical exercise can induce brain plasticity and regulate mental function.  Advances in Exercise      and Sports Physiology, 20, (1), 1-7.

33    National Institutes of Health, National Center for Compementary and Integrative Health web site.  Web page:  NCCIH Clinical Digest for health professionals. What science says, Octover 2015.  Retrieved from                                            http://nccih.nih.gov/health/providers/digest/depression-science#heading1

34  Fagulha, T., Goncalves, B., & Ferreira, A. (2011).  A population-based assesment of midlife portuguese women’s     experience of primenopuase and menopause.  Health Care for Women International, 32, 559-580.

35   Santin, A.P., & Ferlanetto, T.W. (2011).  Role of estrogen in thyroid function and growth regulation.                                         Jornal of Thyroid Research, 2011, article ID 875125, 7 pages.  Doi: 10.461/2011/87525

36   Sakson-Obada, O.l, Wycisk, J. (2015).  The body self and frequency, intensity and acceptance of menopausal symptoms.  Menopause Review, 14, (2), 82-89

37    Shapiro, D., Cook, I.A., Davydov, D.M., Ottaviani, C., Leuchter, A.F., & Abrams, M. (2007).  Yoga as a complementary treatment of depression: Effect of traits and moods on treatment outcome.  Evidence Based Complement Alternative Medicine,  4, (4), 493-502.

38      Morgan, A. (1999).   Sahaja Yoga:  an ancient path to modern mental health? (Unpublished doctoral thesis).        University of Plymouth, Plymouth United Kingdom.  Retrieved from          http://ethos.bl.uk/OrderDetails.do?uir=uk.bl.ethos.580483

39      Wolkowitz, O.M., Reus, V.I., Roberts, E., Manfredi, F., Chan, T., Raum, W.J., Ormistron, S.,      Johnson, R., Canick, J., Brizendine, L., & Weingartner, H. x

Owen M. Wolkowitz

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Affiliations

  • Department of Psychiatry, University of California, San Francisco, USA
  • Center for Neurobiology and Psychiatry, University of California, San Francisco, USA

Correspondence

  • Address reprint requests to Owen M. Wolkowitz, M.D., Department of Psychiatry, University of California, San Francisco, School of Medicine, 401 Parnassus Avenue, Box F-0984, San Francisco, CA 94143-0984.

(1997).    Dehydroepiandrosterone (DHEA) treatment of depression.  Biological Psychiatry 41 (3): 311-318

40    Watson, S., & Mackin, P., (2006).  HPA axis function in mood disorders. Psychiatry 5 (5): 166-170.  Doi: 10.1383/psyt.2006.5.5.166

41    Heaney, J.L.J., Carroll, D., & Phillips, A.C., (2013).  DHEA, DHEA-S and cortisol responses to acute exercise in older adults in relation to exercise training status and sex.   Age (Dordr) 35 (2):395-405.  Doi: 10.1007/s11357-011-9345-y

42    Wolkowitz, O.M., Reus, V.I., Roberts, E., Manfredi, F., Chan, T., Raum, W.J., Ormistron, S., Johnson,        R., Canick, J., Brizendine, L., & Weingartner, H., (1997).  Dehydroepiandrosterone (DHEA) treatment for depression.  Biological Psychiatry 41 (3): 311-318.

43    Body ecology, the way to be website.  Webpage: if you really want to avoid early aging, get to know “DHEA”. Accessed on March 17, 2017.   Accessed at: http://bodyecology.com/articles/avoid_early_aging_dhea.php

44    Health Canada website.  http://webprod.hc-sc.gc.ca/nhpid-        bdipsn/ingredReq.do?id=4639&lang=eng

45   Kornblut, A.E., & Wilson, D., (2005).  How one pill escaped the list of controlled steroids.  The New          York Times, April 17, 2005.  Accessed at: http://www.nytimes.com/2005/04/17/us.how-one-pill-escaped-the-list-of-contoled-steroids.html?_r=o

46   Web MD website.  Webpage: Foods that fight winter depression.  Accessed on March 3rd, 2017.    Accessed at:                 www.webmd.com/depression/fetatrues/foods-that-fight-winter-depression#1

47     Sharma, R.P., & Coulombe, R.A., (1987).  Effects of repeated doses of aspartame on serotonin and its metabolite in various regions of the mouse brain.  Food Chemical Toxicology, 24 (8): 565-568.

48   WebMD website.  Webpage: Thyroid symptoms and solutions. Retrieved from,         www.webmd.com/depresson/guide/depression-the-thyroid-and-hormones

49   Health span website, webpage: Soothing menopausal stress with vitamin B.  Accessed:             www.healthspan.co.uk/menopause-advice/depression/soothing-menopuasal-stress-with-vitamin-b

50  New York Times website.  Webpage: The New York Times Health Guide, Anemia.  Retrieved from:                 www.nytimes.com/health/guides/disease/anemia/symptoms.html

51   Aggrawal, B.B., & Harikumar, K.B., (2009).  Potential therapeutic effects of Curcumin, the anti- inflammatory agent, against neurogenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases.  The International Journal of Biochemistry & Cell Biology,      41 (1): 40-59.


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