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Natural Medicine Journal

February 7, 2018

Lifestyle and Herbs for Polycystic Ovary Syndrome

Results from a 3-month trial

Megan Chmelik

ND
Lifestyle modification alone appears to improve some aspects of polycystic ovary syndrome. A recent study suggests that a treatment plan that includes both lifestyle changes and select herbal supplements may achieve even greater improvement in some patients.

Reference

Arentz S, Smith C, Abbott J, et al. Combined lifestyle and herbal medicine in overweight women with polycystic ovary syndrome (PCOS): a randomized controlled trial. Phytother Res. 2017;31:1330-1340.

Study Objective

To determine if lifestyle intervention plus herbal medicine is more effective in the treatment of polycystic ovary syndrome (PCOS) than lifestyle intervention alone

Design

Three-month randomized, nonblinded clinical trial

Participants

The study enrolled 122 Australian women, aged 18 to 44 years, with BMI greater than or equal to 24.5 kg/m2 and PCOS diagnosed by the Rotterdam Criteria. To avoid potential adverse herb-drug interactions, women taking estrogens, progestogens, and/or antidepressants were excluded.

Intervention

All participants received lifestyle intervention that included dietary modification and initiation of regular physical activity. Working together, a nutritionist and exercise physiologist provided information about aerobic and resistance training and counseled participants on identifying calorie content, nutrient-dense foods, and low glycemic index carbohydrates. Participants then collaborated with these practitioners to develop individualized plans. A pragmatic approach was taken to better reflect the realities of clinical practice.

The herb combination selected in the formula used in this trial was meant to target multiple pathophysiologic mechanisms of PCOS.

The experimental group (n=60) received herbal medicine intervention in addition to lifestyle modification plans. Extracts of Glycyrrhiza glabra, Paeonia lactiflora, Cinnamomum verum, and Hypericum perforatum, in equal parts and equivalent to 750 mg of dry herb, were formulated into single tablets. Participants were instructed to take 3 tablets, once daily. Tribulus Forte (MediHerb), containing Tribulus terrestris extract equivalent to 13.5 g aerial parts, was given as a separate tablet. Participants were instructed to take 3 tablets Tribulus Forte once daily during the follicular phase of the menstrual cycle only. Oligomenorrheic women started on day 5 of their cycles and those with amenorrhea started within 1 week of trial commencement. All were instructed to continue for 10 consecutive days.

Outcome Measures

Length of menstrual cycle was the primary outcome measure. Serum concentrations of reproductive hormones, glucose and insulin sensitivity, anthropometric measurements, quality of life, levels of depression, anxiety, and stress, pregnancy and birth outcomes, and safety (determined by blood pressure and adverse reactions) were also assessed. Assessments were performed at baseline and 3 months.

Key Findings

Self-reporting revealed that 73% of all participants were engaging in at least 150 minutes of exercise weekly and that 86% were making health-conscious dietary decisions (energy-sparse, low glycemic index carbohydrates, with 2 servings of fruit and 5 servings of vegetables daily). Compliance with the herbal protocol was high, with all except 2 returning empty bottles at conclusion of the trial.

At baseline, mean menstrual cycle length was 106 days in the experimental group and 109.5 days in the control. After 3 months, significant reductions in cycle lengths were found in the experimental group (−42.3 days; P<0.001), resulting in a greater proportion (55% vs 24.2%) achieving normalcy (20-34 days). Improvement in the control group was minimal (−2.9 days).

While there were no significant differences in testosterone, sex hormone-binding globulin (SHBG), follicle stimulating hormone (FSH), or free androgen index (FAI) between groups, an increase in estradiol (P=0.03) and a decrease in luteinizing hormone (LH; P=0.04) was noted in the experimental group. Fasting insulin, weight, BMI, waist circumference, and blood pressure were also positively impacted by the herbal medicine intervention. Higher rates of conception (P=0.01) were achieved in the experimental group, though live birth rates were not significantly different between the 2 groups.

The experimental group reported greater amounts of positive change in depression, anxiety, stress, and perceived quality of life.

Adverse events were noted by 2 participants in the experimental group. One developed flu-like symptoms (headache, lethargy, and joint pain) and the other experienced abnormal uterine bleeding. Resolution occurred following discontinuation of all herbs.

Practice Implications

Polycystic ovary syndrome is a common endocrinopathy that affects approximately 6% to 18% of reproductive-aged women.1 Diagnosis requires that at least 2 of the following 3 criteria are met: chronic oligoovulation or anovulation; biological and/or clinical signs of hyperandrogenism; and/or polycystic ovarian morphology. However, symptom presentation and severity is highly variable. Four phenotypes have been identified using the aforementioned criteria, in order to delineate the variations in presentation (A: hyperandrogenism (HA) + ovulatory dysfunction (OD) + polycystic ovarian morphology (PCOM); B: HA + OD; C: HA + PCOM; D: OD + PCOM).2 Categorization based on BMI (lean vs overweight/obese) is also commonly used in research and clinical practice.

Past research suggests that there are biochemical, hormonal, and metabolic dissimilarities between lean and obese type PCOS. A 2017 review by Goyal et al summarized these findings and concluded that there is a higher prevalence of insulin resistance, increased risk of developing metabolic syndrome and other comorbid conditions, and poorer treatment outcomes in those who are obese.3 Given that 50% to 80% of women with PCOS fall into this category (obese), appropriate treatment is necessary to improve symptomology and minimize future risk.4

Weight loss is a first-line intervention for improving androgen levels, insulin resistance, and menstrual regularity in obese PCOS patients.5 Two separate papers from 2015 revealed significant benefit from modest weight loss achieved through dietary modification. The first reported improvements in menstrual cycle regularity and hirsutism (assessed using modified Ferriman-Gallwey scores) with reductions in weight, BMI, and waist circumference.6 The second noted lower androgen levels, improved insulin sensitivity, decreased DNA damage, and reduced cardiometabolic risk factors with a 3.5% average weight loss.7 A 2016 paper looked at the potential benefit of delaying fertility treatment until lifestyle modifications had been implemented. Those who lost weight prior to initiating treatment had higher rates of ovulation and live birth.8

It appears that lifestyle modification alone will improve aspects of PCOS, though the findings of this paper suggest that the addition of herbs will result in even more favorable outcomes. The same authors who conducted this study published a 2014 review on herbal medicine for the treatment of PCOS. Their goal was to identify herbs that had been well-studied and shown to improve some aspect of the condition. From 33 trials, they found the following herbs to have the most preclinical and clinical evidence: Vitex agnus-castus, Cimicifuga racemosa, Cinnamomum cassia, Tribulus terrestris, Glycyrrhiza glabra, and Paeonia lactiflora.9 Of these, 4 were selected for use in their 2017 clinical trial.

The herb combination selected in the formula used in this trial was meant to target multiple pathophysiologic mechanisms of PCOS. While there are numerous documented medicinal actions for each, the authors selected those most likely to have an impact on PCOS. Glycyrrhiza glabra and Paeonia lactiflora were chosen for their androgen-lowering abilities. Cinnamomum verum was used to increase insulin sensitivity. Hypericum perforatum, though not commonly thought of as an herb specific to PCOS, was included for its antidepressant effects.10 Research has shown that there is a higher incidence of mood disorders in women with PCOS, so it is not a surprise that those in the experimental group demonstrated improvements in depression, anxiety, stress, and overall quality of life.11-13

Tribulus terrestris has been used in Chinese and Ayurvedic medicine to treat a variety of conditions, including sexual dysfunction, cardiovascular disease, and diabetes.14 The authors of the present study chose to use Tribulus terrestris because past research revealed that consumption of this herb leads to a temporary, but significant, rise in serum FSH levels.15 An inverse and abnormally elevated ratio of LH to FSH has been noted in some, but not all, PCOS patients; one study reports an incidence of 45.4%.16 Because FSH deficiency has been shown to impair follicle maturation, it is proposed that supporting production of FSH may increase rates of ovulation.17 Also of interest, a 2016 study by Samani et al found that 1,000 mg of Tribulus terrestris taken daily for 3 months resulted in lower blood glucose, total cholesterol, and low-density lipoprotein levels in women with type 2 diabetes mellitus.18 Given these findings, it is reasonable to suspect that the antihyperglycemic and antihyperlipidemic properties may help manage the metabolic component of the condition.

The outcomes of this study highlight the benefits of using herbal medicine in conjunction with foundational lifestyle modifications for the treatment of PCOS. The significant reduction in cycle length observed in the experimental group is a promising finding. Perhaps continued treatment, beyond 3 months, would result in even greater improvement. Given the results, a trial of this herbal combination seems to be a worthwhile consideration for patients presenting with obese PCOS. For those with lean PCOS and/or those without suspected insulin resistance, it is unclear if and how they would benefit; however, utilizing the same approach for selecting herbs, with emphasis on pathophysiologic mechanisms, is likely to result in a formula that addresses both symptoms and underlying pathology.

Categorized Under

Megan Chmelik

ND

Megan Chmelik, ND, is a recent graduate of National University of Natural Medicine in Portland, Oregon. Her next steps include joining an integrative women’s healthcare practice, where she will carry out her passion for treating PCOS and infertility. Before starting naturopathic medical school, she worked for Rena Bloom, ND, and Jacob Schor, ND, FABNO. She attributes her passion for writing review articles to Schor, who taught her how to use PubMed and mentored her as she fine-tuned her skills.

References

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  2. Lizneva D, Suturina L, Walker W, Bratka S, Gavrilova-Jordan L, Azziz R. Criteria, prevalence, and phenotypes of polycystic ovary syndrome. Fertil Steril. 2016:106(1):6-15.
  3. Goyal M, Dawood A. Debates regarding lean patients with polycystic ovary syndrome: a narrative review. J Hum Reprod Sci. 2017;10 (3):154-161.
  4. Deng Y, Zhang Y, Li S, et al. Steroid hormone profiling in obese and nonobese women with polycystic ovary syndrome. Sci Rep. 2017;7(1):14156.
  5. Ibáñez L, Oberfield SE, Witchel SF, et al. An International Consortium update: pathophysiology, diagnosis, and treatment of polycystic ovarian syndrome in adolescence. Horm Res Paediatr. 2017;6:307-331.
  6. Marzouk T, Sayed Ahmed W. Effect of dietary weight loss on menstrual regularity in obese young adult women with polycystic ovary syndrome. J Pediatr Adolesc Gynecol. 2015;28(6):457-461.
  7. Soares NP, Santos AC, Costa EC, et al. Diet-induced weight loss reduces DNA damage and cardiometabolic risk factors in overweight/ obese women with polycystic ovary syndrome. Ann Nutr Metab. 2016;68(3):220–227.
  8. Legro RS, Dodson WC, Kunselman AR, et al. Benefit of delayed fertility therapy with preconception weight loss over immediate therapy in obese women with PCOS. J Clin Endocrinol Metab. 2016;101(7):2658-2666.
  9. Arentz S, Abbott JA, Smith CA, Bensoussan A. Herbal medicine for the management of polycystic ovary syndrome (PCOS) and associated oligo/amenorrhoea and hyperandrogenism; a review of the laboratory evidence for effects with corroborative clinical findings. BMC Complement Altern Med. 2014;14:511.
  10. Arentz S, Smith CA, Abbot J, Fahey P, Cheema BS, Bensoussan A. Combined lifestyle and herbal medicine in overweight women with polycystic ovary syndrome (PCOS): a randomized controlled trial. Phytother Res. 2017;31(9):1330-1340.
  11. Hollinrake E, Abreu A, Maifeld M, Van Voorhis BJ, Dokras A. Increased risk of depressive disorders in women with polycystic ovary syndrome. Fertil Steril. 2007;87(6):1369-1376.
  12. Adali E, Yildizhan R, Kurdoglu M, et al. The relationship between clinico-biochemical characteristics and psychiatric distress in young women with polycystic ovary syndrome. J Int Med Res. 2008;36(6):1188-1196.
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  14. Zhu W, Du Y, Meng H, Dong Y, Li L. A review of traditional pharmacological uses, phytochemistry, and pharmacological activities of Tribulus terrestris. Chem Cent J. 2017;11(1):60.
  15. Milanov S, Maleeva A, Tashkov M. Tribestan effect on the concentration of some hormones in the serum of healthy subjects. Sofia, Bulgaria: Company documentation, Chemical Pharmaceutical Research Institute; 1981.
  16. Banaszewska B, Spaczyński RZ, Pelesz M, Pawelczyk L. Incidence of elevated LH/FSH ratio in polycystic ovary syndrome women with normo- and hyperinsulinemia. Rocz Akad Med Bialymst. 2003;48:131-134.
  17. Solorzano CM, Beller JP, Abshire MY, Collins JS, McCartney CR, Marshall JC. Neuroendocrine dysfunction in polycystic ovary syndrome. Steroids. 2012;77(4):332-337.
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