Herbals for PCOS and Associated Infertility
By: Kelsey Williamson
Editor’s Note: Spices like cinnamon have become synonymous with the holidays. But do herbs like cinnamon provide benefits beyond mulled wine and holiday cheer? Kelsey Williamson, a former FACTS Elective student, summarized a review of evidence for the use of herbal medicine — including Cinnamomum cassia for management of polycystic ovarian syndrome (PCOS) and associated menstrual disturbances. Traditionally, management of PCOS-related infertility has involved clomiphene or metformin, and, more recently, letrozole and myo-inositol, but in this review of laboratory evidence, Arentz et al. discuss a variety of complementary and alternative interventions to improve fertility outcomes. [1]
Introduction
Polycystic Ovarian Syndrome (PCOS) is an endocrine disorder characterized by polycystic ovaries, chronic anovulation, hyperandrogenism, and insulin resistance. Women diagnosed with PCOS commonly struggle with irregular menses, acne, hirsutism, and infertility. Luteinizing hormone or LH levels are often abnormally elevated in relation to FSH and serum androgens may also be high. Current treatments include oral contraceptive pills (OCPs) to produce regular withdrawal bleeds, metformin to decrease insulin resistance, and clomiphene citrate for ovulation induction. For women with PCOS who are trying to conceive, symptom management with OCPs is not an option and clomiphene citrate (Clomid®) can lead to mood swings and gastrointestinal complaints. Herbal therapies may provide an alternative option for these patient populations.
“Women diagnosed with PCOS commonly struggle with irregular menses, acne, hirsutism, and infertility.”
Methodology
In this 2014 meta-analysis, Arentz et al. searched for herbal therapies with both pre-clinical and clinical research for the management of PCOS in the scientific literature [1]. The researchers identified 18 pre-clinical studies and 15 clinical studies discussing six different herbal interventions: Vitex agnuscastus, Cimicifuga racemosa, Tribulus terrestris, Glycyrrhiza spp., Paeonia lactiflora, and Cinnamomum cassia. Herbs with either pre-clinical or clinical research alone were excluded from the review.
Results
Vitex agnus-castus (chaste berry)
Vitex agnus-castus, also known as chaste tree or chaste berry, has long been used to treat menstrual irregularity. In animal models, it has been found to bind to dopamine type 2 (DA2), histamine, serotonin (5-HT), beta-estrogen, and mu opioid receptors. In one human study, Vitex agnus-castus lowered prolactin in female participants as effectively as the pharmaceutical Bromocriptine. Two pre-clinical and one clinical trial noted that Vitex agnus-castus binds to beta-estrogen receptors, and one preclinical trial noted it binds to alpha-estrogen receptors in the pituitary. Two randomized clinical trials (RCTs) of Vitex agnus-castus demonstrated improved pregnancy rates, and three showed improved cycle regularity. One of these studies specifically analyzed the luteal phases, noting an increase from 3.4 days to 10.5 days (p <0.005) after Vitex agnus-castus (Strotan® 20 mg daily). Though all of the studies are small and used a variety of Vitex agnus-castus products, the clinical outcomes support the animal findings. Vitex agnus-castus shows promise in balancing hormones, regulating cycles, and enhancing fertility for women with PCOS.
“Two randomized clinical trials (RCTs) of Vitex agnus-castus demonstrated improved pregnancy rates, and three showed improved cycle regularity.”
Cimicifuga racemosa (black cohosh)
Cimicifuga racemosa, or black cohosh, lowered LH levels in 2 of 3 animal models by binding alpha-estrogen receptors in the brain. Three RCTs had a similar effect, in addition to increasing luteal progesterone and improving endometrial thickness. Black cohosh used in conjunction with clomiphene citrate improved pregnancy rates compared to clomiphene alone (43.3% versus 20.3% in one study, and 38.% versus 17.2% in the other). Cimicifuga racemosa also out-performed clomiphene when each was taken individually, though results were not statistically significant: 14% versus 8%, respectively. In that same study, Cimicifuga racemosa lowered LH levels more than clomiphene (p = 0.007). However, these studies were non-blind studies, and data should be interpreted with caution due to possible bias. Additionally, although limited data prohibits widespread use, women struggling with side effects of clomiphene or women inclined to choose herbals over pharmaceuticals could consider black cohosh for ovulation induction.
“Black cohosh used in conjunction with clomiphene citrate improved pregnancy rates compared to clomiphene alone (43.3% versus 20.3% in one study, and 38.% versus 17.2% in the other).”
Tribulus terrestris (bindii)
Two animal studies showed positive ovulation induction in PCOS rats following several doses of Tribulus terrestris. In one human clinical trial, 250 mg of Tribulus terrestris was administered daily for five days in the follicular phase to eight healthy women. Researchers found a significant increase in FSH and an increase in estradiol. Another clinical trial compared Tribulus terrestris to ovulation-inducing drugs and found equivalent ovulation induction for women with oligo/anovulatory infertility: Tribulus terrestris 60% and clomiphene 47%. However, this study had potential bias, and methods of group allocation were unclear. External sources have not reported the use of Tribulus terrestris in clinical practice at this time, so further human research is required before providing supplemental guidelines.
Glycyrrhiza spp. (licorice)
Studies investigating Glycyrrhiza glabra (European licorice) and Glycyrrhiza uralensis (Chinese licorice) both found associated androgen-lowering effects. Rats given Glycyrrhiza spp. demonstrated reduced free and total testosterone by increasing 17-beta estradiol through aromatization. PCOS rats given Glycyrrhiza also had improved ovulation rates. In one human study, nine healthy women who received 7g of Glycyrrhiza spp. every day found decreased serum androgen levels (p < 0.05). For 32 women with PCOS taking Spironolactone, those taking Glycyrrhiza had a lower testosterone level on day 4 of treatment (p < 0.05), which mitigated common side effects of the “androgen surge” typically associated with Spironolactone administration. Both human trials were small, single-armed studies further limited by the presence of healthy women only in the former study and the variability of herbal ingredients.
Paeonia lactiflora (white peony)
Glycyrrhiza spp. with Paeonia lactiflora is commonly used by women’s health herbalists. One rat study demonstrated rats with reduced testosterone and LH after they received a combination of the two herbs. In two single-arm trials, one with eight infertile oligomenorrheic/ hyperandrogenic women and one with 34 women with oligo/amenorrheic PCOS, testosterone and LH levels decreased following the administration of Paeonia lactiflora and Glycyrrhiza uralensis, reaching statistical significance in the PCOS trial (n=34; p < 0.001). In the study including eight infertile women, ovulation induction improved with this combination therapy, although the results were not statistically significant.
Paeonia lactiflora has also been studied in combination with Cinnamomum cassia. Pre-clinical studies analyzing their combined effect on cultured human granulosa cells of women undergoing IVF showed increased estradiol and progesterone production. One clinical trial treated 157 women with amenorrhea and 42 women with oligo/amenorrhea with Unkei-to (7.5g daily x 8 weeks), a supplement containing both Paeonia lactiflora and Cinnamomum cassia. Ovulation occurred in 61.3% of primary amenorrheic women and 27.3% of secondary amenorrheic women after two months of therapy. The women were also found to have reduced LH levels. One limitation of both the pre-clinical and clinical trials is that the Unkei-to extract contained additional herbal ingredients; therefore, a causal relationship cannot be attributed solely to the Paeonia lactiflora and Cinnamomum cassia combination.
Cinnamomum cassia (Chinese cinnamon)
Cinnamomum has also been studied alone for its effect on insulin resistance. A rat model found that Cinnamomum cassia matched metformin in reduction in testosterone and LH, as well as reduction of insulin resistance. A small pilot RCT among overweight women with PCOS also showed an improved metabolic profile.
Discussion
In summary, Vitex agnus-castus lowered prolactin levels, Cimicifuga racemosa lowered LH, and Tribulus terrestris raised FSH levels. Comparing these herbs to their pharmaceutical counterparts, Vitex agnus-castus appeared to be as effective as Bromocriptine at lowering prolactin. Cimicifuga racemosa and Tribulus terrestris also showed promise: both were as effective as clomiphene for ovulation induction, although studies were limited. Additionally, a combination of Paeonia lactiflora and Glycyrrhiza uralensi was found to improve ovulation induction. Glycyrrhiza spp., Paeonia lactiflora and Cinnamomum cassia all lowered androgens levels, with Cinnamomum cassia treatment outcomes comparable to metformin when it comes to reduction in testosterone and LH. Paeonia lactiflora alone also increased both estradiol and progesterone and Cinnamomum cassia alone improved insulin sensitivity. None of the herbs caused reported side effects. Also, it is important to note that all of the studies were small and carry risk for bias.
Current recommendations for herbal management of PCOS to regulate hormones include the combination of peony and licorice (Paeonia and Glycyrrhiza) or licorice alone. Dr. Aviva Romm, a well-cited physician, midwife and herbalist recommends the peony/licorice combination, Vitex agnus-castus (chaste berry) and Cimicifuga racemosa (black cohosh), for hormone balance. She also recommends 1.5 g daily of cinnamon for improved insulin resistance. Though not an herbal, she also highly recommends 4 g daily of myo-inositol plus 400 mcg of folic acid as a more effective and natural treatment compared to metformin. [2]
Other sources present similar recommendations following successful case studies. The American Botanical Council cited a case report (n=1) of a six-herb cocktail containing Vitex agnus-castus, Glycyrrhiza glabra, Paeonia lactiflora, Gymnema sylvestre, echinacea, and schisandra. The herbal treatment in combination with a low-carbohydrate diet nearly eliminated the patient’s mastalgia, acne, and hirsutism; normalized her lipid panel; and led to a 12% weight loss. [3]
“Beyond medicines and herbals, managing PCOS is best achieved by a lifestyle change.”
Beyond medicines and herbals, managing PCOS is best achieved by a lifestyle change. This may combine dietary modification to decrease inflammation with stress reduction to promote adrenal health [2]. Herbals provide an additional treatment modality when these lifestyle changes are insufficient, too burdensome, or too slow for a woman hoping to conceive. Additionally, these herbals offer an alternative to oral contraceptives for PCOS management in women desiring improved fertility, as well as a more natural alternative for women requiring treatment for ovulation induction. Thus, herbal remedies should remain part of the conversation around PCOS treatment for both hormone regulation and ovulation induction. Further research conducted within larger sample populations and that utilized precise dosages and preparations should be the next step to implement more widespread applications.
Sources
[1] 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. doi:10.1186/1472-6882-14-511
[2] Romm A. PCOS: The natural prescription. Aviva Romm, MD. 2018. http://avivaromm.com/pcos-natural-prescription
[3] Stafford Mader, L. Treating PCOS Naturally: Clinical experience and scientific evidence support medicinal herbs, nutritional supplements, and lifestyle interventions to treat symptoms of this common female endocrine disorder. HerbalGram. 2013;10(3).
ABOUT THE AUTHOR
Kelsey Williamson
Kelsey Williamson is a third-year OB-GYN resident at the University of Texas Austin Dell Medical School. She was able to take part in the FACTS elective during her fourth year of medical school at the University of North Carolina. Her interest in natural family planning (NFP) began with her own health and faith. She later learned about FACTS through the American Association of Pro-Life Obstetricians and Gynecologists. With the training from the FABM elective and from incredible mentors over the years, Kelsey hopes to continue to share and utilize FABMs throughout her career.
