Table 1.
Clinical trial studies on medicinal plants used for treatment of PCOS patients
| No | Authors /country/ year | Scientific name | Part/ compound | Sample size | Duration of study | Results |
|---|---|---|---|---|---|---|
| 1 | Borzoei A, et al., Iran 2017 [25] | Cinnamomum zeylanicum Blume | Cinnamon bark powder prepared as capsule | 84 | 8 weeks |
Significant differences of serum TAC (P = 0.005) and MDA (P = 0.014) between cinnamon & placebo groups after the intervention. ↑ TAC (P = 0.001) without statistical decrease in serum MDA level (P = 0.102) in cinnamon group at the end of study compared to the baseline. ↓total cholesterol and LDL and ↑ HDL serum levels in cinnamon group at the end of the study compared to the baseline (P < 0.05). No significant change on serum TG level in cinnamon group. |
| 2 | Forouhari S, et al., Iran 2013 [26] | Glycine max (L.) Merr. | Soy flour as a loaf of soy bread | 42 | 2 months | No significant effects on serum FSH, Estradiol, and testosterone level following soy bread consumption after the intervention (P > 0.05). |
| 3 | Arentz S, et al., Australia 2017 [27] | Cinnamomum verumj. Presl, Glycyrrhiza glabral., Hypericum perforatum L., Paeonia lactiflora Pall. and Tribulu s terrestri s L. | Herbal extracts as tablets | 122 | 3 months |
↓Oligomenorrhoea of 32.9% in herbal medicine plus lifestyle group compared with lifestyle alone P < 0.01). ↓ BMI (P < 0.01);↓Waist circumference (P < 0.01);↓ insulin (P = 0.02), and ↓ LH (P = 0.04);↓blood pressure (P = 0.01); improvement in the quality of life (P < 0.01), depression, anxiety, and stress (P < 0.01); and pregnancy rates (P = 0.01) in combination group compared with lifestyle intervention alone. |
| 4 | Tehrani HG, et al., Iran 2017 [28] | Camellia sinensis L. | Camellia sinensisL.as tablets (Green Teadin pills) | 60 | 12 weeks | ↓ Weight (P = 0.031), ↓ fasting insulin (P < 0.0001), and ↓ free testosterone (P < 0.0001) after treatment between groups (green tea & control). |
| 5 | Swaroop A, et al., India 2015 [29] | Trigonella foenum-graecum L. | Hydro-alcoholic extract of seeds as capsules | 50 | 3 months | ↑ LH (p = 0.045) and ↑ FSH (P = 0.010), ↓ LH/FSH ratio (not statistically significant), ↓ ovarian volume, ↓ cyst size in 47 subjects, complete resolving of cysts in 36 patients, regular menstrual cycles in 71% of subjects, ↑ Hb levels, ↓ ALP, no significant change in WBC, AST, ALT, BUN, and creatinine and 12% pregnancy after intervention compared to the baseline. No serious side effect in Agnugol group. |
| 6 | Shayan A, et al., Iran 2016 [30] | Vitex agnus-castus L. | Dry extract as Agnugol tablet | 120 | 3 months | No difference in the length of menstruation, intervals of menstrual cycles, and the number of pads in two groups (Agnugol & Metformin) after the intervention. No serious side effect in Agnugol group. |
| 7 | Hajimonfarednejad M, et al., Iran 2017 [31] | Cinnamomum cassia (L.) J.Presl. | Barks powder | 66 | 12 weeks | ↓ Weight, ↓ BMI, ↓ waist circumference (not statistically significant), ↓ fasting insulin (P = 0.024), HOMA-IR (P = 0.014), ↓ LDL (P = 0.049) and HDL (P = 0.033) after the intervention in cinnamon group in comparison with the placebo group. Both groups received medroxy progesterone acetate at the beginning of the study. No serious side effect in cinnamon group |
| 8 | Paul Grant, UK 2009 [32] | Mentha spicata L. | tea | 42 | 30 days | ↓ Free and total testosterone, ↑ LH, ↑ FSH, ↓ degree of hirsutism scored by the modified DQLI in spearmint tea group (P < 0.05), ↓Ferriman-Galwey score of hirsutism (not statistically significant) between two groups (spearmint & placebo) at the end of the study (P = 0.12). No side effect was reported. |
| 9 | Shahnazi M, et al., Iran 2016 [33] | Vitex agnus-castus L. | Fruit extract | 70 | 3 months |
Normalization the menstrual cycle duration in 68.6% of the LD group and 60% of the extract participants (no statistically significant difference between the two groups (P = 0.45). ↓ Free testosterone, prolactin, and DHEAS level in the LD and the extract groups at the end of study (no statistically significant difference between the two groups). Mood changes and Spotting were reported in Vitex group (no statistically significant difference between groups). |
| 10 | Chen J, et al. Japan 2010 [34] | Grifola frondosa | MSX tablets, containing Grifola frondosa extract and its dried powder | 72 | 12–16 weeks | Ovulation in 76.9% MSX and in 93.5% CC groups but not significant (P = 0.124). Epigastralgia in two MSX group patients. |
| 11 | Kuek S et al.,China 2011 [35] | – | A capsule containg 11 herbs | 47 | 3 months | ↓ Testosterone, ↓ SHBG, ↓ FAI, ↓ FINS, ↓ ovarian volume, ↑ DHEAS (P < 0.05), without change in FPG in Tian Gui group after treatment compared before. ↓ Testosterone in the three groups (Tian Gui, metformin and Dian), but no statistically significant difference between the groups. Significant changes in DHEA-S and SHBG between the three groups. No side effect was reported. |
| 12 | Shahin A.Y and Mohammed S.A., Egypt 2014 [36] | Cimicifuga racemosae (L.) Nutt.(CR) | Dry extract of CR rhizomein the form of film-coated tablets | 206 | 2 months | ↓ Mid-cycle LH (P = 0.001), ↑ progesterone (P = 0.001) and ↑ estradiol in the second half (P = 0.01), ↑endometrial thickness (P = 0.001), ↑pregnancy rate (P < 0.01) in CC + CR group compared to the CC group alone. |
| 13 | Chan C. et al., Hong Kong 2006 [37] | – | Lung Chen tea leaves as capsule | 34 | 3 months | ↓ Body weight (2.4%) after treatment in green tea group but not statistically significant. No remarkable change in hormone levels and biochemical profiles except TG between two groups after treatment. ↑ TG in green tea group compared to the placebo at the end of the study. No side effect was reported. |
| 14 | Ebrahimi-Mamaghani M, et al., Iran 2014 [38] | Allium cepa L. | Raw red onions | 54 | 8 weeks | ↓ Total cholesterol, ↓ LDL in two groups (high onion & low onion), but further in the high-onion group after treatment. No significant change in FBS, TG, and LDH by onion treatment. |
| 15 | Ke Wu X, et al., Chinese 2016 [39] | – | Berberine in the form of capsule | 644 | 6 months | ↑ Accumulative live births, ↑ conception, ↑ pregnancy, and ↑ ovulation rates in the letrozole and combination groups (letrozole + berberine) after treatment compared to berberine group. No serious side effect among the three groups (letrozole, berberine, and combination groups). |
| 16 | Ushiroyama T, et al., Osaka 2001 [40] | Paeonia lactiflora Pall. with Cinnamomum cassia (L.) J. Presll. | Unkei-to | 100 | 8 weeks | ↓ LH and ↑ estradiol and making dominant follicle in Unkei-to group. Improvement of menstrual cyclicity of 50% PCOS subjects in Ukei-to group, but no statistically significant difference between the two groups (Unkei-to & control). |
| 17 | Hassanzadeh Bashtian M, et al., Iran 2013 [41] | Trigonella foenum-graecum L. | Hydroalcoholic extract of seeds | 58 | 8 weeks |
↓ Significant in polycystic-appearing ovaries in ultrasound scans in extract group at the end of the study (P = 0.01). No significant changes in BMI, HOMA-IR, QUICKI, testosterone, 17-α hydroxy progesterone levels, and Ferriman–Gallwey score in both groups (herbal extract & placebo) Normalizing menstrual cycle in 12 women with oligo-amenorrhea in extract group. Both groups received metformin during the study. |
| 18 | Kumarapeli M, et al. Sri Lanka 2018 [42] | Anethum graveolens L. Asparagus racemosus Willd. | Satapushpa Shatavari Powder (SSP)5 g TDS/.oral Satapushpa ShatavariGrita (SSG), 60 ml / daily /enema | 60 | 2 weeks | ↓ Ovarian volume, and normalized menstrual cycle at the end of the study compared to the baseline in three groups (oral, rectal and oral + rectal). Significant ↑ endometrial thickness, and ↓ hirsutism rate in oral+rectal group after intervention compared to other groups. |
| 19 | Jamilian M and Asemi Z., Iran 2016 [43] | Glycine max (L.) Merr. | Soy isoflavone supplements as capsule | 70 | 12 weeks | ↓ Insulin (P < 0.001), ↓ HOMA-IR andHOMA-B (P < 0.001), ↑ QUICKI (P = 0.01), ↓ free androgen index (P < 0.001),↓ TG (P = 0.04), ↑ plasma total glutathione (P = 0.04), ↓ MDA (P = 0.001) after treatment compared to the placebo group. |
| 20 | Kort DH, Lobo RA Columbia 2014 [44] | Cinnamomum Verum J. Presl. | Cinnamon as supplement | 45 | 6 months |
Significant improvement in menstrual cyclicity and ovulatory cycle in cinnamon group compared with baseline and placebo. No considerable change in markers of insulin resistance, serum androgen, SHBG levels, weight, and ovarian volume in both groups. No serious adverse effect. |
| 21 | Wang J G et al., USA 2007 [45] | Cinnamomum verum J. Presl. | Extract | 15 | 8 weeks | ↓ FBS (P > 0.03), ↑ QUICKI (P > 0.03), ↓ HOMA-IR (P > 0.03), ↓ in mean 2hppbsand improved insulin sensitivity in the extract group but not statistically different from the control (placebo). |
| 22 | Kamel Hany H. Egypt 2012 [46] | Cimicifuga racimosa (L.) Nutt. (CR) | Extract | 100 | 3 months | ↓ LH (P = 0.007), ↓ FSH/LH ratio (P = 0.06), ↑ progesterone (P = 0.0001), ↑ endometrial thickness (P = 0.0004), ↑ ovulation (P = 0.0001) and fewer side-effects in CR compared to the CC group after intervention. ↑ Pregnancy rate in CR compared to CC group but not statistically significant. |
| 23 | Lai L, et al., Chinese2017 [47] | – | Granulated extracts as a tea from 14 to 20 herbs | 40 | 6 months | Significant improvement in menstrual rates in two groups (standardized Chinese hebal medicine & individualized chinese herbal medicine) but no statistically significant difference between groups (P = 0.26), ↓ hirsutism scores but not significant (P = 0.09) in two groups. No significant change in BMI or weight in two groups at the end of the study. |
| 24 | Kalgaonkar S et al., USA 2011 [48] | Prunus dulcis (Mill.) Juglans regiaL. | Walnuts, Almonds | 36 | 6 weeks | ↓ LDL (P = 0.05),↓Apo protein B (P < 0.03), ↑ insulin response (P < 0.02), ↑ PUFA, ↓ HgBA1c (P = 0.0006) and ↑ SHBG (P = 0.0038) in walnut group. ↓ LDL (not statistically significant) and ↓ FAI (P = 0.0470) in almond group. ↑ Adiponectin in two groups (walnuts or almonds). |
| 25 | Wiweko B and Susanto C. A. Indonesia 2017 [49] | Lagerstroemia spesiosa (L.)and Cinnamomum burmanni Blume | Extract as tablet | 38 | 6 months |
↓ AMH level in 2 groups after treatment but further reduction in metformin group with more side effects. Significant ↓ BMI in herbal group after treatment. All subjects received metformin during the study. |
| 26 | Mombaini E, et al., Iran 2017 [50] | Camellia sinensisL. | Camellia sinensis L. leaf powder as tablets | 50 | 45 days |
Significant ↓in weight, BMI, waist circumference, and body fat percentage after the intervention in the green tea group, but no significant difference between the two groups (green tea & placebo) was observed. No significant difference in the inflammatory factors in comparison with between- and within- groups at the end of the study. No serious side effect. |
| 27 | Khani B, et al. Iran 2011 [51] | Glycine max (L.) Merr. | Soy supplement as Genistein capsules | 146 | 3 months |
Significant ↓ LH, ↓TG, ↓LDL, ↓DHEAS and ↓testosterone after treatment in the Genistein group. No significant difference in HDL and FSH serum levels in two groups (Genistein and placebo) before and after intervention. |
| 28 | Farzana F, et al., India 2015 [52] | Linum usitatissimum L. | Flaxseed powder | 32 | 3 months | ↓ Ovarian volume, number of follicles (P < 0.01), improvement in menstrual cyclicity and pregnancy (40% and 10% respectively), Ns change in hirsutism, BW, and BS after intervention compared to before. |
| 29 | An Y, et al., China 2014 [53] | – | Berberine hydrochloride as tablets | 150 | 3 months |
↓ Testosterone, ↓ free androgen, ↓ FBS, ↓ fasting insulin, ↓ HOMA-IR, ↑ SHBG, ↑ pregnancy rate, and ↓ severe ovarian hyperstimulation syndrome in berberine and metformin group compared to placebo after treatment.↓ BMI, ↓ lipid parameters and ↓ FSH, ↑ live birth rate (P = 0.047) and less frequent unwanted events in berberine compared to metformin group after treatment. . |
| 30 | Jalilian N, et al., Iran 2013 [54] | Stachys lavandulifolia Vahl | Dried aerial parts of wood betony (AWB) | 66 | 3 months | ↓ Prevalence rate of AUB symptoms in two groups (AWB & MPA). Adverse events in 24.2% cases of MPA compared to 45.5% in AWB but less serious side effects for AWB compared to MPA. The odds for adverse reaction of MPA = 0.40 (95% CIs: 0.14–1.19, P value = 0.099) time odds of AWB. Remarkable changes of sonographic findings in AWB after treatment compared to MPA (P = 0.036). |
| 31 | Mirmasoumi G, et al., Iran 2017 [55] | Linum usitatissimum L. | Flaxseed oil in form of capsule | 60 | 12 weeks | ↓ Insulin values, ↓ HOMA-IR (P = 0.01), ↓ Ferriman–Gallwey score (P = 0.001), ↑ QUICKI (P = 0.01), ↓ TG (P = 0.01), ↓ VLDL (P = 0.01), ↓ CRP (P = 0.004) in treatment group compared to placebo after intervention. Ns change in hormonal profile and plasma nitric oxide at the end of the study in treatment group. No adverse event in treatment group. |
| 32 | Haj-Husein Iet al., Jordan 2015 [56] | Origanum majorana L. | Marjoram tea | 25 | 1 month | ↓ DHEAS, ↓ fasting insulin (P < 0.05), in marjoram groups after treatment. ↓ HOMA-IR in intervention group compared to placebo (P < 0.05). |
| 33 | Liang, Y et al., China 2016 [57] | – | Chinese medical decoction (CCD) | 40 | 2 months | ↑ Oocyte retrieval number, ↑ 2pronuclear fertilization rate, ↑ embryo rate and ↓ ROS in treatment group compared to control. |
| 34 | Liu Y, Mao LH., China 2013 [58] | – | Dan-zhi Xiao-yao (Chinese medicine formulation) as pills | 60 | 3 menstrual cycles | Significant↓ Insulin, ↓ LH, ↓ testosterone after treatment compared to before in two groups (P < 0.05) but no significant difference between the groups. No remarkable change in BMI between two groups after treatment. Significant improvement in PMS and menstrual symptoms in integrative group. Higher ovulation and pregnancy rate in integrative versus western group (86.01% vs 65.5% and 60% vs 36.7%, respectively). |
| 35 | Naeimi S A et al., Iran 2018 [59] | Nigella sativa L. | powdered seed in form of capsule | 10 | 4 menstrual cycles | Significant ↓ cholesterol, ↓ TG, ↓ FBS, ↓ Insulin, ↓ AST, ↓ LH, and ↓ HOMA-IR, ↑ menstrual cycle/ month and ↓ menstrual cycle interval after intervention. |
| 36 | Borzoei A, et al., Iran 2017 [60] | Cinnamomum zeylanicum Blume | Cinnamon bark powder prepared as capsule | 84 | 8 weeks | Significant FBS, ↓ Insulin, ↓ HOMA-IR,↓ cholesterol, ↓ LDL, ↓weight and ↑ HDL in cinnamon group compared to placebo. Significant ↓ TG, ↓ BMI in cinnamon group compared to its base line. No remarkable change in adiponectin in both groups. |
| 37 | Esmaeilinezhad Z, et al., Iran 2019 [61] | PunicagranatumL. | juice | 92 | 8 weeks | Significant ↓ HOMA-IR, ↓BMI, weight and waist circumferences in synbiotic pomegranate juice and synbiotic beverage compared to baseline and control group. Significant ↓ testosterone in synbiotic pomegranate juice and synbiotic beverage compared with baseline |
| 38 | Moini A, et al., Iran 2018 [62] | Apium graveolens L.and Pimpinella anisum L. | powdered seeds in form of capsule | 72 | 4 menstrual cycles | ↑ menstrual cyclicity, ↓ testosterone and ↓ LH/FSH in intervention group compared to the metformin group |
| 39 | Heidary M, et al., Iran 2018 [63] | Matricaria chamomilla L. | Chamomilpowder as capsule | 80 | 3 months | Significant ↓ testosterone after treatment in chamomile group. No remarkable change in LDL, HDL, TG, DHEA, and LH/FSH in treatment and control group. |
| 40 | Armanini D, et al., Italy 2006 [64] | Glycyrrhiza glabra L. | licorice powder | 32 | – | No remarkable change in blood pressure and no complain of symptoms related to volume depletion in spironolactone plus licorice group compared to spironolactone treatment. |
| 41 | Mokaberinejad R, et al., Iran, 2019 [65] | Foeniculum vulgare Mill. | Fennel seed infusion | 61 | 6 months | ↓ Menstrual cycle interval and ↓ dysmenorrhea severity in treatment group compared to metformin group after 3 and 6 months. No adverse event in treatment group. |
| 42 | Ding CF. et al., China 2014 [66] | – | Chinese medicine formulation as decoction | 355 | 3menstrual cycles |
Significant ↓ spiral artery pulsatility index,↓ resistance index, ↑endometrial thickness, in group 2 (clomiphene + human menopause gonadotropin + human chorionic gonadotropin + Cangfu daotan) compared to group 1 (clomiphene + human menopause gonadotropin + human chorionic gonadotropin). ↓ HOMA-IR in group 2 after treatment compared to before. |
N.S; not significant, ↑; increased, ↓; decreased TAC; total antioxidant capacity, MDA; malondialdehyde, LDL; low-density lipoprotein, HDL; high-density lipoprotein, VLDL; very low-density lipoprotein cholesterol, TG; triglycerid, FSH; follicle-stimulating hormone, LH; luteinizing hormone, Hb; hemoglobin, HgBA1c;hemoglobin A1c or glycosylated hemoglobin, BMI; body mass index, CC; clomifene citrate, HOMA-IR; homeostatic model assessment insulin resistance, HOMA-B;homeostasis model of assessment β-cell function DQLI; dermatology quality of life index, LD; combined low-dose oral contraceptives, DHEAS;dehydroepiandrosterone sulfate, CC; clomiphene citrate, AST; aspartate transaminase, ALT; alanine transaminase, ALP; alkaline phosphatase, BUN; blood urea nitrogen, WBC; white blood cell, SHBG; sex hormone-binding globulin, T; testosterone, LDH; lactate dehydrogenase, FBS; fasting blood sugar, FAI; free androgen index, FINS; fasting insulin, FPG;fasting plasma glucose, QUICKI; quantitative insulin sensitivity check index, PMS; premenstrual syndrome, AMH; anti-müllerian hormone, BS; blood suger, BW; body weight, AUB; abnormal uterine bleeding, ROS; reactive oxygen species, CRP; C-reactive protein, LDH; lactate dehydrogenase, PUFA; polyunsaturated fatty acids, MPA; medroxyprogesterone acetate, Met; metformin, 2hppbs; 2 h postprandial blood suger