Another list of select research studies that have influenced my clinical practice in gynecological and primary care for women. I hope these selections benefit you and your patients.
Curcumin as an Effective Added Treatment for Major Depressive Disorder
Did you know that curcumin, a component of turmeric (Curcuma longa), has antidepressant activity? Natural medicine has much to offer individuals who suffer from mild to moderate depression, and increasingly, we have things to offer for those with major depression. One of the problems with conventional treatments is that nearly 50% of patients with major depressive disorders discontinue their medication due to side effects. Finding treatments that do not cause side effects then becomes a much-needed area of optimal management. Curcumin, a component of turmeric rhizome has been studied in several clinical trials, but the current paper is a meta-analysis that evaluated the safety and effectiveness of curcumin in treating major depressive disorder.
The meta-analysis of the literature that was searched included those that met the following criteria: (1) human study, (2) quantitative analysis, (3) intervention and control group, (4) curcumin was an independent intervention, (5) study addressed only major depressive disorder, (6) depression was measured with standardized scales, and (7) the study was in English. Studies were also rated according to quality and the data from all the studies were converted into Hamilton Depression Rating Scale scores.
A total of 1757 studies were identified, and six met all the inclusion criteria which totaled 342 patients (n=177 curcumin and n=165 control). There were four randomized controlled trials, one crossover study, and one open-label study. All patients received an antidepressant prescription medication in addition to either curcumin (1 g/day, n = 5 studies or 500 mg/day, n = 1 study) or placebo. Five of the studies rated strong in quality and one was moderate.
In this meta-analysis there was a significant reduction in major depressive symptoms with curcumin treatment compared with control. In addition, several subgroup analyses demonstrated that curcumin had a significant benefit in middle-aged patients but not older-aged patients, although age ranges were not defined; curcumin had a significant benefit in patients treated for > 6 weeks but not in patients treated for < 6 weeks; 500 mg/day of curcumin did not have an effect but 1,000 mg/day did have a significant benefit; and curcumin had a significantly greater benefit in those patients who only had major depressive disorder vs. those with major depressive disorder and other chronic health problems.
Commentary: This appears to be the first meta-analysis of the effect of curcumin on major depressive disorder. Summary conclusions are that curcumin is effective in reducing symptoms of depression in patients with major depressive disorder and are already taking prescription antidepressants, and that curcumin is more effective in middle-aged patients. Effective doses were 1 g/day for > 6 weeks. A few cautionary notes with this meta-analysis are that there were only 6 studies; only two doses of curcumin were evaluated; the piperine used to enhance curcumin and/or the doses of curcumin may not have been optimal and that the study was quite short term for such a chronic condition. On the other hand, the methodology the authors used was rigorous and I am encouraged by the research on curcumin and depression.
Tribulus terrestris, low libido in Postmenopausal Women
This clinical trial evaluated the effects of treating postmenopausal women with hypoactive sexual desire disorder (HSDD) using Tribulus terrestris. All women received testing including mammography, vaginal ultrasounds, and serum levels of prolactin, thyroid stimulating hormone, total testosterone and sex hormone binding globulin before enrollment. Study participants were randomized to two groups with the treatment group receiving three pills of 250 mg of T. terrestris for 120 days and the control group receiving placebo for 120 days.
The Female Sexual Function Index (FSFI) and the Sexual Quotient Female Version (QS-F) questionnaires were used to assess female sexual function. A total of 36 healthy postmenopausal women with low libido were selected to participate in this study in Brazil. All women were between 1 and 10 years postmenopausal and were between 43 and 65 years old. Women were excluded if they had interpersonal relationship problems or had partners with sexual problems.
There was a total of 36 women, with 20 in the study group and 16 in the placebo group, with three drop outs in each group. The total mean score and scores of each of the six FSFI questionnaire domains before and after treatment did not show any significant difference between the two groups. Women receiving the T. terrestris scored significant improvements in all six domains as did the placebo group, with the exception of lubrication which did not improve in the placebo group.
After 120 days of treatment with T. terrestris, the QS-F indicated significant improvement in the domains of desire, arousal/lubrication, pain and anorgasmia with the placebo group showing no improvements in any of these domains.
The initial testosterone levels in both groups did not vary before and after the treatment, although there was a significant increase in the levels of free and bioavailable testosterone in the T. terrestris group with no increase in the placebo group.
Commentary: To my knowledge, this is the first study suggesting a treatment effect of T. terrestris for HSDD in postmenopausal women. While there was improvement yet no difference between treatment group and placebo for the FSFI domains except lubrication, which did improve more in the treatment group, that is in fact important in comfort during vaginal penetration. And, if sex is anticipated to be comfortable and pain free, then the desire to have sex tends to improve. The other scale, the QS-F questionnaire is a tool designed to assess sexual function in Brazilian women specifically. It could be interpreted that this questionnaire is more representative of results in Brazilian women, which might explain the difference in results between the questionnaires.
Premenstrual Syndrome – Comparison of Chamomile to Mefenamic acid
The purpose of this study was to compare the effects of chamomile extract and mefenamic acid (MA) on the severity of symptoms of premenstrual syndrome (PMS). This study was conducted on 90 women in Iran, with 45 women in each group. Women were included if they were single, ages 18-35, normal body mass index, a regular menstrual cycle and with a diagnosis of PMS and without chronic mental or physical diseases. The participants were divided into the two groups, and one group received chamomile capsule 100 mg three times a day from day 21 until the onset of the menstrual period, and for two cycles. Group two received the MA capsules of 250 mg three times a day and again, from day 21 until the first day of the menstrual period, for two cycles.
The mean values of severity of general physical and psychological symptoms in the premenstrual period were similar between the two groups prior to the onset of the treatment. The mean reduction in overall intensity of symptoms after the two courses of treatment was significantly different between the two groups, and the chamomile was modestly more effective, after the treatment of two cycles. Specifically, the reduction of psychological symptoms was more effective with chamomile and there were similar results in the relief of the physical symptoms between the two groups. The results also indicated that the chamomile was more significantly effective for anger and irritability and mefenamic acid was more effective for arthralgia, muscular aches, and abdominal and pelvic pains.
Commentary: PMS is one of the most common problems in reproductive aged women with a prevalence of 62.4% to 83.1%. The most frequent physical symptoms of PMS include abdominal bloating, fatigue, breast tenderness and headache. The common behavioral and psychological symptoms include irritability, anger, depression, increased appetite and loss of concentration. PMS symptoms start any time after ovulation and then end with the onset of menses or towards the end of menses. In other studies, chamomile has been found to be effective against anxiety and anger.
It is interesting that the treatment cycle was only 7 days. For those women with more severe intensity and longer duration of PMS symptoms, from ovulation through the end of the cycle, I would likely give the chamomile all month long, or at least the 2 plus weeks.
Myo-inositol Plus Selenium Reverses Thyroid Antibodies in those with Subclinical Hypothyroidism
Chronic autoimmune hypothyroidism is one of the most common autoimmune diseases affecting more than 10% of women and 2% of men. It primarily affects those who are 30-50 years old. An elevated thyroid stimulating hormone (TSH) and autoantibodies such as anti-thyroglublin (TgAb) and anti-thyroid peroxidase (TPOAb) are the typical features of this condition. Most hypothyroid disease is an autoimmune process, Hashimoto’s being the most prevalent. A mild hypothyroid condition is called subclinical hypothyroidism with a TSH between 3-6 IU/ml. The American Thyroid Association’s guidelines have a TSH upper limit of 4.12. Some professionals have proposed the TSH should be no higher than 2.5 or 3.0, while others are even more steering towards 1.5-2.0.
In the current study, a total of 168 patients with Hashimoto’s hypothyroidism with TSH levels between 3 and 6 IU/ml were randomized into two groups: one received Myo-inositol 600 mg daily plus 83 mcg of selenium (75 women and 9 men); the other group received just the 83 mcg selenium per day (74 women and 10 men). This was done for 6 months. TSH, TPOAb and TgAb levels were significantly decreased in patients treated with the combined myo-inositol/selenium after 6 months. There was also a significant increase in free thyroxine (free T4) in the combination supplement group, as well as an improvement in quality of life and subjective symptomatology. The increase in thyroid hormones concentration was observed in both treatment groups, but it was significantly higher in those receiving the combination.
Commentary: The take home in this study is that these doses of myo-inositol plus selenium can improve TSH levels, reduce thyroid antibody levels, and improve subjective symptoms in women and men who have subclinical (a TSH of 3-6) Hashimoto’s thyroid disease. This is great news for those individuals for whom their doctor will not prescribe thyroid hormones because their TSH is normal or normal enough, yet they have symptoms without other explanations including fatigue, muscle weakness and mood related issues. TSH is a very sensitive marker of thyroid function, more so than thyroid hormone levels such as free T3 and free T4. This is especially true in individuals with subclinical cases. When the TSO is above 10, thyroid hormone prescriptions are a well proven treatment. Of the many mechanisms of myoinositol in thyroid function, it is involved in one of the first steps of thyroid hormone production. Previous trials have reported reduction of TPOAb with selenium after 6 months and we know that selenium deficiency leads to glutathione peroxidase inactivity which may induce oxidative harm for thyroid cells leading to thyroid damage and fibrosis.
- Al-Karawi, D., et al. Phytother Res. 2016;30(2):175-183.
- Dias de Souza K., et al. Menopause 2017; 23;(11): 1252-1256.
- Sharifi, F., et al. Complementary Therapies in Clinical Practice 2014; 20:81-88
- Basciani, N. European Review for Medical and Pharmacological Sciences 2017;21(2):51-59