In the newest of the St. John’s wort studies in perimenopausal/menopausal women, a total of 100 Iranian women with an average age of 50 participated in a randomized, double-blind, placebo-controlled clinical trial comparing St. John’s wort with placebo in the treatment of hot flashes.[1] 50 women received 20 drops three times daily of St. John’s wort extract (Hypericin) that contained hypericin 0.2 mg/mL and 50 women received a placebo of distilled water. The study duration was two months. Clinical exams and interviews were performed at baseline, 4 weeks and 8 weeks. Treatment effectiveness was measured evaluating frequency, duration and severity of hot flashes as the main objective of the study.

In women taking St. John’s wort, the frequency began to decline during the 1^st and 2^nd months, but showed more improvement during the 2^nd month. There was no statistical change in hot flash frequency during the first month of placebo but did improve during the second month. Women who used St. John’s wort showed more improvement in hot flash frequency than placebo. The decline in duration of hot flashes was statistically significant at week 8 and the decline was much more evident in the St. John’s wort group. The severity of hot flashes was relieved in the St. John’s wort group during the 2 months of treatment and was more significant in the second month. Women in the placebo group did not show any significant decrease in severity of hot flashes during the 1^st month, but they did have some improvement during the 2^nd month, but not as great as those women in the St. John’s wort group.

Comments

St. John’s wort has emerged as an important clinical tool in treating perimenopausal/menopausal women—for hot flashes and/or depression and/or mood swings, and/or sleep problems either as an encapsulated standardized extract from 300 mg twice per day to three times per day, or a tincture/liquid extract ½ tsp 2-3 times per day, or in combination with other menopause therapies such as black cohosh, maca extract, kava or others.

Reference

[1] Abdali K, Khajehei M, Tabatabaee R. Effect of St. John’s wort on severity, frequency, and duration of hot flashes in premenopausal, perimenopausal and postmenopausal women: a randomized, double-blind, placebo-controlled study. Menopause 2010;17(2): 326-331.

Peer-reviewed research studies were located in various data-bases searching for studies investigating vitamin D and depression, seasonal affective disorder, PMS, postpartum depression, perinatal depression, depressive disorder or mood disorder in women. Eleven studies were initially identified, but five were eliminated because they did not meet the inclusion criteria. Of these six studies, four reported significant results showing an association between low serum 25 (OH) D levels and symptoms of a mood disorder, SAD, major depressive disorder, or PMS. One study of major depression and one on SAD did not report an association. Only one of the four positive studies was a randomized controlled trial.

Vitamin D receptors are involved in the regulation of glucocorticoid signaling and dysfunctional glucocorticoid signaling and increased glucocorticoids have been implicated in major depressive disorder. Other biochemical mechanisms may also exist, associating vitamin D with mood disorders.

I look forward to more research on specific mood disorders in women and vitamin D levels.

References:

Murphy P, Wagner C. Vitamin D and mood disorders among women: an integrative review. J Midwifery Women’s Health 2008;53:440-446.

Commentary

This study on a Maca preparation adds to the growing body of evidence utilizing Maca for menopause related symptoms. Having significant effects on anxiety and depression is terrific, but many women – in this study appear to be independent of any measurable influence on sex hormones or SHBG and presumably therefore independent of any action related to the activity of beta-sitosterol, found in Maca. These findings are not consistent with Meissner et al. (Meissner H et al. Use of gelatinized Maca [Lepidium peruvianum] in early postmenopausal women- a pilot study. Int J Biomed Sci 2005;1:33-45) who reported an elevation in LH and estradiol and a decrease in FSH. These variable results may be due to differences in dosing, type of commercial preparation used in each study, species or variety of Lepidium from which the preparations are made, extraction protocols and delivery techniques. The effect on depression and anxiety are consistent in several studies and it is thought that the flavonoids in Maca inhibit monoamine oxidase activity. The improvement in sexual function in postmenopausal women observed in this study is consistent with research using Maca in men and also in rodents.

References

• Brooks N, Wilcox G, Walker K, et al. Beneficial effects of Lepidium meyenii (Maca) on psychological symptoms and measures of sexual dysfunction in postmenopausal women are not related to estrogen or androgen content. Menopause 2008;15(6):1157-1162.

Pregnancy is demanding in it’s own unique way: hormonal changes, increased nutritional demands, changes in sleep and eating patterns. Regular exercise, good healthy eating habits, a prenatal supplement, regular sleep, and moderating one’s work load, are usually enough to maintain energy throughout the pregnancy. Some women may become anemic during pregnancy and simple tests can detect this followed by simple nutrients as supplementation. At times, other health problems emerge during the pregnancy that can cause fatigue such as hypothyroid and diabetes. With good prenatal care, these can be detected and treated appropriately.

The cycles or phases of hormonal change such as the monthly premenstrual time, and the perimenopause transition can challenge what is called our stress adaptation mechanisms. There are three phases to this stress response which are regulated in large part, by our adrenal glands. The initial phase is the alarm reaction, or fight-or-flight response. This is triggered by reactions in the brain that cause the pituitary gland to produce a hormone, which causes the adrenals to secrete adrenaline as well as other stress related hormones. The alarm phase is usually very short lived. The next phase is the resistance reaction, which allows us to continue to deal with stress, after the fight-or-flight response has worn off. Hormones such as cortisol and other corticosteroids secreted by the adrenal cortex are in motion here and responsible for the resistance reaction. These hormones stimulate the conversion of protein to energy so that we have adequate fuel, after our glucose reservoirs have been used. The resistance reaction provides the energy and stabilizes our circulation under times of stress, as well as enabling us to deal with the emotional aspects of stress, fight infections and continue to perform our tasks. If the stress insult is prolonged and the resistance reaction is extended beyond our body’s capabilities to maintain balance, we become at risk for significant health care problems and end up in the final stage of general adaptation syndrome— exhaustion. In the exhaustion phase, our adrenal glands
have become depleted of hormones called glucocorticoids, and our body has a loss of potassium. In this phase, the body’s cells and tissues do not receive enough glucose or other nutrients to function properly.

As the exhaustion phase continues, our cells and organs in general feel the tremendous demand, and our metabolism is extremely challenged. Now we enter what we might call cellular fatigue and literally, our cells don’t get enough fuel to drive their function. This stress to our system takes a toll and nutritional status declines and disease status increases.

Premenstrual syndrome and perimenopause are their own kind of stress on the system. During these times, many women find their threshold of tolerating stress decreases. The complicated interaction of our hormones and our brain chemistry challenges our stress adaptation mechanisms, and fatigue can result. These fluctuating levels, both decreases and increases, in hormones such as estrogen, progesterone, cortisol and thyroid, interact with brain neurotransmitters such as serotonin, dopamine, GABA, and others, that affect our emotional and physical responses to life, to stressors in our environment, to insults, and even to infections.

Different circumstances call for different approaches, and if persistent fatigue is something that plagues you, it is important to consult with a licensed health care practitioner to determine the cause. A good medical history, physical exam, and selected laboratory tests can determine if the cause is low thyroid, anemia, an infectious agent, low or high blood sugar, or a serious illness. Licensed alternative practitioners will also have tools and perspectives to consider food sensitivities, toxicities, neurotransmitter imbalances, hormonal status and something we call adrenal fatigue syndrome.

A condition alternative medicine often calls “adrenal fatigue”, is a unique contribution to understanding a sometimes elusive problem such as fatigue.

Adrenal gland function and its production of hormones are vital performance tasks in our response to stress and our larger responses in our general adaptation syndrome. Nutritional and herbal support for a person who displays symptoms of intense or prolonged stress, and/or a fatiguing of the ability to adapt to the stress, can play a critical role in supporting our adrenal glands to adapt. An abnormal adrenal response, whether it is deficient or excessive hormone release, can be in large part addressed with key nutrients such as pantothene, B6, zinc, magnesium and vitamin C. These nutrients play a critical role in the optimal function of the adrenal glad and in the manufacture of adrenal hormones. Levels of these nutrients can be diminished during times of stress. Urinary excretion of vitamin C is increased during stress. Pantothene is also important during times of high stress or in individuals with adrenal fatigue. A deficiency of pantothenic acid results in fatigue, headaches, insomnia and more. Notable botanicals can also support adrenal function and enhance resistance to stress such as Siberian and Panax ginseng. These ginsengs are referred to as general tonics or adaptogens. Both Chinese and Siberian ginseng can be used to restore vitality in individuals who are chronically fatigued or who have decreased mental and physical performance and/or stamina. These ginseng species have been shown to act as tonics and anti-stress agents, enhancing the ability to cope with both physical and emotional stressors., , Individuals who take ginseng often report an increase in vitality, well being, increased mood, competence at work, mental and physical performance and reduced feelings of stress and anxiety. Rhodiola is well known amongst the Eastern Europeans for its ability to enhance energy, stamina and endurance. rhodiola appears to increase the chemicals that provide energy to the muscle of the heart and to prevent the depletion of adrenal hormones induced by acute stress.

Ashwagandha is also a significant adaptogen providing adrenal and immune support, , for increasing resistance to environmental stressors and as a general tonic. Ashwagandha contains several important active constituents including withanolides. Its mechanisms of action include pain relief, antioxidant effects, reducing inflammation, stimulating thyroid function, as well as respiratory and immune function. Some researchers have claimed that ashwagandha as an antistressor effect. It appears that it may suppress stress induced increases in dopamine receptors in the brain.

Astragalus has been used historically for strengthening and regulating the immune system, as a tonic, antioxidant, anti-inflammatory, antibacterial antiviral and to protect the liver. A lengthy list for sure. Although there is insufficient evidence to support the effectiveness of all of these uses, there is preliminary research that it is positive in some areas. Astragalus extracts seem to be able to restore or improve immune function in immune deficient cases. It may be able to restore suppressed T-cell function in cancer patients.7 Abnormal liver enzyme tests have improved in people chronic hepatitis when taking Astragalus. Astragalus is also thought to increase cardiac output and may be beneficial in individuals with congestive heart failure and compromised blood flow to the heart muscle. 8

We’re all familiar with our favorite spaghetti sauce that contains basil, but we may not know that this same plant, also known as Holy basil is a rich source of vitamin C, calcium, magnesium, potassium and iron. Holy basil has been gaining some attention due to experimental studies in humans on blood glucose. Elevated glucose levels were lowered by 21 mg/dl and lowering glucose after a meal, was also a positive effect of the basil. Many individuals with adrenal dysfunction, have increased glucose levels due to the increased cortisol as a result of stress.

Shisandra is plant most familiar to those who use Chinese herbs. In traditional Chinese medicine, schisandra is used for many common problems, including physical fatigue. Schisandra is used for improving immune function, recovery after surgery, increasing physical performance and endurance, and for increasing resistance to disease and stress. Schisandra is also possibly effective for improving concentration. It is thought that the variety of lignans found in the fruit, are the active constituents in schisandra.

Maca, or Peruvian Ginseng, may be one of the most important plants having a diverse effect on the female reproductive system. Traditionally, it has been used for chronic fatigue syndrome, enhancing energy, stamina and overall energy. In the female reproductive system, its use for enhancing fertility, regulating the menstrual cycle, treating common menopause symptoms and to increase libido has been familiar to the traditional peoples of Peru and elsewhere, for many a generation. Studies soon to be published, will be able to document some of its specific effects for menopausal women.

This type of herbal/nutritional support is especially helpful for those who have been determined to have adrenal fatigue. Symptoms such as fatigue, low vitality, low libido, depression, anxiety, poor memory, low stamina, and difficulty handling the premenstrual phase and the perimenopausal transition are key indications of adrenal fatigue.

Some women who have premenstrual fatigue or perimenopausal fatigue, may need additional hormonal support as well. This may include actually using hormones as medicines, but also may involve improving the metabolisim of our hormones. These considerations can best be addressed utilizing a comprehensive approach with a licensed naturopathic physician who has both the alternative medicine perspective, as well as the ability to prescribe various hormones such as progesterone, estrogen, testosterone, cortisol and thyroid.

The best approach to fatigue is to find out the cause. Don’t just ignore your fatigue and “gut it out” and don’t make assumptions about the cause of your fatigue. With good health care team approach utilizing your insights, your reading and natural foods store resources, a naturopathic physician, and possibly medical doctor or other allied practitioners, you can be more assured of understanding the cause and therefore the best solutions.

ReferencesÂ

• Farnsworth N, et al. Siberian Ginseng: Current status as an adaptogen. Economic Medicinal Plant Research 1985;1: 156-215.
• Hikino H. Traditional remedies and modern assessment: The ase of Ginseng. In R.O.B. Wijeskera, ed. The Medicinal Plant Industry (Boca Raton, FL: CRC Press, 1991), 149-166.
• Shibata S, et al. Chemistry and Pharmacology of Panax. Econ Med Plant Research 1985;1:217-284.
• Hallstrom C, Fulder S, Carruthers. Effect of Ginseng on the performance of nurses on night duty. Comp Med East and West 1982;6:277-282.
• Maslova L, Kondrat’ev B, Maslov L, Lishmanov I. The cardioprotective and antiadrenergic activity of an extract of Rhodiola rosea in stress. Eksp Klin Farmakol 1994;57:61-63. (Article in Russian).
• Upton R, ed. Ashwagandha root (Withania somnifera): Analytical, quality control, and therapeutic monograph. American Herbal Pharmacopoeia 2000;April: 1-25.
• Sun Y, Hersh E, Talpaz M, et al. Immune restoration and/or augmentation of local graft versus host reaction by traditional Chinese medicinal herbs. Cancer 1983;52(1): 70-3.
• Upton R, Ed. Astragalus Root: analytical, quality control, and therapeutic monograph. Santa Cruz, CA: Am Herbal pharmacopoeia; 1999; 1-25.
• Agrawal P, Rai V, Singh R. Randomized placebo-controlled, single blind trial of holy basil leaves in patients with noninsulin-dependent diabetes mellitus. Int J Clin Pharmacol Ther. 1996;34(9): 406-409.
• Upton R, ed. Schisandra Berry: Analytical, Quality and Control, and Therapeutic Monograph. Santa Cruz, CA: American Herbal Pharmacopoeia 1999; 1-25.

The first study followed 436 women without a history of depression, over 8 years. Correlation of hormonal changes with any new onset of depression was recorded. 116 women developed an increase in depressed moods and 59 met the clinical criteria for a diagnosis of depression. 108 women denied depression.

The women who developed depression were 2.5 times more likely to develop clinical depression during the perimenopausal transition compared to premenopause. In addition, their depression symptoms during perimenopause were associated with greater variations in serum estradiol levels, higher body weight, increased hot flashes. The associations with serum estradiol were considered significant.

Freeman E, Sammel L. Lin H, Nelson D. Associations of hormones and menopausal status with depressed mood in women with no history of depression. Arch Gen Psychiatry. 2006;63:375-382. [Fulltext PDF | Fulltext HTML]

The second study is a prospective cohort of women both with and without histories of depression. The risk of new depression was almost doubled in women entering perimenopause, compared with premenopausal women. This difference appeared to be associated with the presence of hot flashes.

Cohen L, Soares C, Vitnonis A, Otto M, Harlow B., et al. Risk for new onset of depression during the menopausal transition: the Harvard Study of Moods and Cycles. Arch Gen Psychiatry. 2006;63:385-390. [Fulltext PDF | Fulltext HTML]

Comments

Previous studies on the topic of depression in perimenopausal and menopausal women have been inconsistent and difficult to interpret given all the variations in study designs and study population. The two current studies provide clinically useful documentation that perimenopausal women are a group of women vulnerable to depression. One the more interesting aspects of the Freeman et al study was that PMS in the reproductive years was a significant predictor of the onset of depression during perimenopause.

In the Harvard study, while there was a doubling of depression in perimenopausal women, most of the women in the study (83%) in fact experienced no mood changes.

As clinicians, it is important to appreciate that perimenopausal women have increased risk of depression, whether or not they had a previous history of depression; and, greater fluctuations in serum estradiol levels and hot flashes are associated with this perimenopausal depression. At the same time, it appears that most women experience perimenopause without experiencing depression. It may be that there are some perimenopausal women who have a less than optimal adaptive mechanism and are less able to deal with these normal hormonal changes. These are the women we can hope to identify and to help.