Herbal Products Used in Menopause and for Gynecological Disorders
Abstract
:1. Introduction
2. Results
2.1. Black Cohosh (Actaea racemosa L./Cimicifuga racemosa (L.) Nutt.)
2.2. Chaste Tree (Vitex agnus-castus L.)
2.3. Evening Primrose (Oenothera biennis L.)
2.4. Fenugreek (Trigonella foenum-graecum L.)
2.5. Hops (Humulus lupulus L.)
2.6. Red Clover (Trifolium pratense L.)
2.7. Valerian (Valeriana officinalis L. s.l.)
2.8. Soybean (Glycine max (L.) Merr. and Glycine subsp. soja (Siebold & Zucc.) H. Ohashi)
3. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
- Nedrow, A.; Miller, J.; Walker, M.; Ngyren, P.; Hoyt Huffman, L.; Nelson, H.D. Complementary and alternative therapies for the management of menopause-related symptoms: A systematic evidence review. Arch. Intern. Med. 2006, 166, 1453–1465. [Google Scholar] [CrossRef]
- Marjoribanks, J.; Farquhar, C.; Roberts, H.; Lethaby, A.; Lee, J. Long-term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst. Rev. 2017, 7, CD004143. [Google Scholar] [CrossRef]
- Yonkers, K.A.; O’Brien, P.S.; Eriksson, E. Premenstrual syndrome. Lancet 2008, 371, 1200–1210. [Google Scholar] [CrossRef]
- Bernardi, M.; Lazzeri, L.; Perelli, F.; Reis, F.M.; Petraglia, F. Dysmenorrhea and related disorders. F1000Research 2017, 6, 1645. [Google Scholar] [CrossRef] [Green Version]
- Dawood, M.Y. Dysmenorrhea. Clin. Obstet. Gynecol. 1990, 33, 168–178. [Google Scholar] [CrossRef] [PubMed]
- Greendale, G.A.; Lee, N.P.; Arriola, E.R. The menopause. Lancet 1999, 353, 571–580. [Google Scholar] [CrossRef]
- Kupperman, H.S.; Blatt, M.H.; Wiesbader, H.; Filler, W. Comparative clinical evaluation of estrogenic preparations by the menopausal and amenorrheal indices. J. Clin. Endocrinol. Metab. 1953, 13, 688–703. [Google Scholar] [CrossRef] [PubMed]
- Kanadys, W.; Barańska, A.; Błaszczuk, A.; Polz-Dacewicz, M.; Drop, B.; Kanecki, K.; Malm, M. Evaluation of clinical meaningfulness of red clover (Trifolium pratense L.) extract to relieve hot flushes and menopausal symptoms in peri-and post-menopausal women: A systematic review and meta-analysis of randomized controlled trials. Nutrients 2021, 13, 1258. [Google Scholar] [CrossRef] [PubMed]
- Orleans, R.J.; Li, L.; Kim, M.-J.; Guo, J.; Sobhan, M.; Soule, L.; Joffe, H.V. FDA Approval of Paroxetine for Menopausal Hot Flushes. N. Engl. J. Med. 2014, 370, 1777–1779. [Google Scholar] [CrossRef] [Green Version]
- Cheema, D.; Coomarasamy, A.; El-Toukhy, T. Non-hormonal therapy of post-menopausal vasomotor symptoms: A structured evidence-based review. Arch. Gynecol. Obstet. 2007, 276, 463–469. [Google Scholar] [CrossRef]
- Handley, A.P.; Williams, M. The efficacy and tolerability of SSRI/SNRIs in the treatment of vasomotor symptoms in menopausal women: A systematic review. J. Am. Assoc. Nurse Pract. 2015, 27, 54–61. [Google Scholar] [CrossRef]
- Pizzorno, J.E.; Murray, M.T. Textbook of Natural Medicine, 4th ed.; Churchill Livingstone, An Imprint of Elsevier Inc.: St. Louis, MI, USA, 2013; pp. 660–665. [Google Scholar]
- European Medicines Agency (EMA); Committee on Herbal Medicinal Products (HMPC). EMA/HMPC/48744/2017 Assessment report on Cimicifuga racemosa (L.) Nutt., Rhizome; EMA: Amsterdam, The Netherlands; HMPC: London, UK, 2017; Volume 44, pp. 1–64. [Google Scholar]
- European Medicines Agency (EMA); Committee on Herbal Medicinal Products (HMPC). EMA/HMPC/48745/2017 European Union Herbal Monograph on Cimicifuga racemosa (L.) Nutt., Rhizoma; EMA: Amsterdam, The Netherlands; HMPC: London, UK, 2017; Volume 44, pp. 1–8. [Google Scholar]
- Kennelly, E.J.; Baggett, S.; Nuntanakorn, P.; Ososki, A.L.; Mori, S.A.; Duke, J.; Coleton, M.; Kronenberg, F. Analysis of thirteen populations of black cohosh for formononetin. Phytomedicine 2002, 9, 461–467. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- He, K.; Zheng, B.; Kim, C.H.; Rogers, L.; Zheng, Q. Direct analysis and identification of triterpene glycosides by LC/MS in black cohosh, Cimicifuga racemosa, and in several commercially available black cohosh products. Planta Med. 2000, 66, 635–640. [Google Scholar] [CrossRef] [PubMed]
- Reame, N.E.; Lukacs, J.L.; Padmanabhan, V.; Eyvazzadeh, A.D.; Smith, Y.R.; Zubieta, J.K. Black cohosh has central opioid activity in postmenopausal women: Evidence from naloxone blockade and positron emission tomography neuroimaging. Menopause 2008, 15, 832–840. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rhyu, M.R.; Lu, J.; Webster, D.E.; Fabricant, D.S.; Farnsworth, N.R.; Wang, Z.J. Black cohosh (Actaea racemosa, Cimicifuga racemosa) behaves as a mixed competitive ligand and partial agonist at the human μ opiate receptor. J. Agric. Food Chem. 2006, 54, 9852–9857. [Google Scholar] [CrossRef] [Green Version]
- Powell, S.L.; Gödecke, T.; Nikolic, D.; Chen, S.N.; Ahn, S.; Dietz, B.; Farnsworth, N.R.; Van Breemen, R.B.; Lankin, D.C.; Pauli, G.F.; et al. In vitro serotonergic activity of black cohosh and identification of Nω-methylserotonin as a potential active constituent. J. Agric. Food Chem. 2008, 56, 11718–11726. [Google Scholar] [CrossRef] [Green Version]
- Cicek, S.S.; Khom, S.; Taferner, B.; Hering, S.; Stuppner, H. Bioactivity-guided isolation of GABAA receptor modulating constituents from the rhizomes of Actaea racemosa. J. Nat. Prod. 2010, 73, 2024–2028. [Google Scholar] [CrossRef]
- Cui, G.; Leng, H.; Wang, K.; Wang, J.; Zhu, S.; Jia, J.; Chen, X.; Zhang, W.; Qin, L.; Bai, W. Effects of Remifemin treatment on bone integrity and remodeling in rats with ovariectomy-induced osteoporosis. PLoS ONE 2013, 8, e82815. [Google Scholar]
- Choi, E.M. Deoxyactein stimulates osteoblast function and inhibits bone-resorbing mediators in MC3T3-E1 cells. J. Appl. Toxicol. 2013, 33, 190–195. [Google Scholar] [CrossRef]
- Castelo-Branco, C.; Gambacciani, M.; Cano, A.; Minkin, M.J.; Rachoń, D.; Ruan, X.; Beer, A.M.; Schnitker, J.; Henneicke-von Zepelin, H.H.; Pickartz, S. Review & meta-analysis: Isopropanolic black cohosh extract iCR for menopausal symptoms–an update on the evidence. Climacteric 2021, 24, 109–119. [Google Scholar]
- Uebelhack, R.; Blohmer, J.U.; Graubaum, H.J.; Busch, R.; Gruenwald, J.; Wernecke, K.D. Black cohosh and St. John’s wort for climacteric complaints: A randomized trial. Obstet. Gynecol. 2006, 107, 247–255. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bai, W.; Henneicke-von Zepelin, H.H.; Wang, S.; Zheng, S.; Liu, J.; Zhang, Z.; Geng, L.; Hu, L.; Chunfeng, J.; Liske, E. Efficacy and tolerability of a medicinal product containing an isopropanolic black cohosh extract in Chinese women with menopausal symptoms: A randomized, double blind, parallel-controlled study versus tibolone. Maturitas 2007, 58, 31–41. [Google Scholar] [CrossRef] [PubMed]
- Liske, E.; Hänggi, W.; Henneicke-von Zepelin, H.H.; Boblitz, N.; Wüstenberg, P.; Rahlfs, V.W. Physiological investigation of a unique extract of black cohosh (Cimicifugae racemosae rhizoma): A 6-month clinical study demonstrates no systemic estrogenic effect. J. Women’s Health Gender-Based Med. 2002, 11, 163–174. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hostanska, K.; Nisslein, T.; Freudenstein, J.; Reichling, J.; Saller, R. Cimicifuga racemosa extract inhibits proliferation of estrogen receptor-positive and negative human breast carcinoma cell lines by induction of apoptosis. Breast Cancer Res. Treat. 2004, 84, 151–160. [Google Scholar] [CrossRef] [PubMed]
- Vitex agnus-castus L. Plants of the World Online, Kew Science. Available online: http://www.plantsoftheworldonline.org/taxon/urn:lsid:ipni.org:names:865568-1 (accessed on 18 January 2021).
- Schulz, V.; Hänsel, R.; Blumenthal, M.; Tyler, V.E. Rational Phytotherapy: A Reference Guide for Physicians and Pharmacists, 5th ed.; Springer: Berlin/Heidelberg, Germany, 2004; pp. 317–332. [Google Scholar]
- Certo, G.; Costa, R.; D’Angelo, V.; Russo, M.; Albergamo, A.; Dugo, G.; Germanò, M.P. Anti-angiogenic activity and phytochemical screening of fruit fractions from Vitex agnus castus. Nat. Prod. Res. 2017, 31, 2850–2856. [Google Scholar] [CrossRef]
- Chen, S.N.; Friesen, J.B.; Webster, D.; Nikolic, D.; Van Breemen, R.B.; Wang, Z.J.; Fong, H.H.S.; Farnsworth, N.R.; Pauli, G.F. Phytoconstituents from Vitex agnus-castus fruits. Fitoterapia 2011, 82, 528–533. [Google Scholar] [CrossRef] [Green Version]
- Masada, S. Authentication of the botanical origin of Western herbal products using Cimicifuga and Vitex products as examples. J. Nat. Med. 2016, 70, 361–375. [Google Scholar] [CrossRef] [Green Version]
- Oshima, N.; Masada, S.; Suzuki, R.; Yagi, K.; Matsufuji, H.; Suenaga, E.; Takahashi, Y.; Yahagi, T.; Watanabe, M.; Yahara, S.; et al. Identification of New Diterpenes as Putative Marker Compounds Distinguishing Agnus Castus Fruit (Chaste Tree) from Shrub Chaste Tree Fruit (Viticis fructus). Planta Med. 2016, 82, 147–153. [Google Scholar] [CrossRef] [Green Version]
- European Directorate for the Quality of Medicines (EDQM). European Pharmacopoeia (Ph. Eur.), 10th ed.; Council of Europe: Strasbourg, France, 2019. [Google Scholar]
- European Medicines Agency (EMA); Committee on Herbal Medicinal Products (HMPC). EMA/HMPC/606742/2017 European Union Herbal Monograph on Vitex agnus-castus L., Fructus; EMA: Amsterdam, The Netherlands; HMPC: London, UK, 2018; Volume 44, pp. 1–10. [Google Scholar]
- Hoberg, E.; Orjala, J.; Meier, B.; Sticher, O. Diterpenoids from the fruits of Vitex agnus-castus. Phytochemistry 1999, 52, 1555–1558. [Google Scholar] [CrossRef]
- Wuttke, W.; Jarry, H.; Christoffel, V.; Spengler, B.; Seidlová-Wuttke, D. Chaste tree (Vitex agnus-castus)—Pharmacology and clinical indications. Phytomedicine 2003, 10, 348–357. [Google Scholar] [CrossRef] [Green Version]
- Marjoribanks, J.; Brown, J.; O’Brien, P.M.S.; Wyatt, K. Selective serotonin reuptake inhibitors for premenstrual syndrome. Cochrane Database Syst. Rev. 2013, 6, CD001396. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Turner, S.; Mills, S. A double-blind clinical trial on a herbal remedy for premenstrual syndrome: A case study. Complement. Ther. Med. 1993, 1, 73–77. [Google Scholar] [CrossRef]
- Lauritzen, C.; Reuter, H.D.; Repges, R.; Böhnert, K.J.; Schmidt, U. Treatment of premenstrual tension syndrome with Vitex agnus castus controlled, double-blind study versus pyridoxine. Phytomedicine 1997, 4, 183–189. [Google Scholar] [CrossRef]
- Berger, D.; Schaffner, W.; Schrader, E.; Meier, B.; Brattström, A. Efficacy of Vitex agnus castus L. extract Ze 440 in patients with pre-menstrual syndrome (PMS). Arch. Gynecol. Obstet. 2000, 264, 150–153. [Google Scholar] [CrossRef] [PubMed]
- Schellenberg, R. Treatment for the premenstrual syndrome with agnus castus fruit extract: Prospective, randomised, placebo controlled study. Br. Med. J. 2001, 322, 134–137. [Google Scholar] [CrossRef] [Green Version]
- Halaska, M.; Beles, P.; Gorkow, C.; Sieder, C. Treatment of cyclical mastalgia with a solution containing a Vitex agnus castus extract: Results of a placebo-controlled double-blind study. Breast 1999, 8, 175–181. [Google Scholar] [CrossRef]
- Ma, L.; Lin, S.; Chen, R.; Wang, X. Treatment of moderate to severe premenstrual syndrome with Vitex agnus castus (BNO 1095) in Chinese women. Gynecol. Endocrinol. 2010, 26, 612–616. [Google Scholar] [CrossRef]
- He, Z.; Chen, R.; Zhou, Y.; Geng, L.; Zhang, Z.; Chen, S.; Yao, Y.; Lu, J.; Lin, S. Treatment for premenstrual syndrome with Vitex agnus castus: A prospective, randomized, multi-center placebo controlled study in China. Maturitas 2009, 63, 99–103. [Google Scholar] [CrossRef]
- Neghab, N.; Zamani, M.; Torabian, S. Therapeutic Effect of Vitex Agnus Castus in Patients with Premenstrual Syndrome. Acta Med. Iran. 2012, 50, 101–106. [Google Scholar]
- Csupor, D.; Lantos, T.; Hegyi, P.; Benkő, R.; Viola, R.; Gyöngyi, Z.; Csécsei, P.; Tóth, B.; Vasas, A.; Márta, K.; et al. Vitex agnus-castus in premenstrual syndrome: A meta-analysis of double-blind randomised controlled trials. Complement. Ther. Med. 2019, 47, 102190. [Google Scholar] [CrossRef]
- Atmaca, M.; Kumru, S.; Tezcan, E. Fluoxetine versus Vitex agnus castus extract in the treatment of premenstrual dysphoric disorder. Hum. Psychopharmacol. 2003, 18, 191–195. [Google Scholar] [CrossRef]
- Ciotta, L.; Pagano, I.; Stracquadanio, M.; Di Leo, S.; Andò, A.; Formusco, C. Psychic aspects of the premenstrual dysphoric disorders. New therapeutic strategies: Our experience with Vitex agnus castus. Minerva Ginecol. 2011, 63, 237–245. [Google Scholar] [PubMed]
- Schellenberg, R.; Zimmermann, C.; Drewe, J.; Hoexter, G.; Zahner, C. Dose-dependent efficacy of the Vitex agnus castus extract Ze 440 in patients suffering from premenstrual syndrome. Phytomedicine 2012, 19, 1325–1331. [Google Scholar] [CrossRef] [PubMed]
- Milewicz, A.; Gejdel, E.; Sworen, H.; Sienkiewicz, K.; Jedrzejak, J.; Teucher, T.; Schmitz, H. Vitex agnus castus extract in the treatment of luteal phase defects due to latent hyperprolactinemia. Results of a randomized placebo-controlled double-blind study. Arzneimittelforschung 1993, 43, 752–756. [Google Scholar] [PubMed]
- Kilicdag, E.B.; Tarim, E.; Bagis, T.; Erkanli, S.; Aslan, E.; Ozsahin, K.; Kuscu, E. Fructus agni casti and bromocriptine for treatment of hyperprolactinemia and mastalgia. Int. J. Gynecol. Obstet. 2004, 85, 292–293. [Google Scholar] [CrossRef]
- Pakgohar, M.; Moradi, M.; Jamshidi, A.; Mehran, A. Assessment of Vitex agnus-castus L. Extract Effect on Treatment of Premenstrual Syndrome. J. Med. Plants 2009, 8, 98–107. [Google Scholar]
- Gerhard, I.; Patek, A.; Monga, B.; Blank, A.; Gorkow, C. Mastodynon® bei weiblicher Sterilität. Complement. Med. Res. 1998, 5, 272–278. [Google Scholar] [CrossRef] [PubMed]
- Van Die, M.D.; Burger, H.; Teede, H.; Bone, K. Vitex agnus-castus extracts for female reproductive disorders: A systematic review of clinical trials. Planta Med. 2013, 79, 562–575. [Google Scholar] [CrossRef] [Green Version]
- Cerqueira, R.O.; Frey, B.N.; Leclerc, E.; Brietzke, E. Vitex agnus castus for premenstrual syndrome and premenstrual dysphoric disorder: A systematic review. Arch. Women’s Ment. Health 2017, 20, 713–719. [Google Scholar] [CrossRef]
- Verkaik, S.; Kamperman, A.M.; van Westrhenen, R.; Schulte, P.F.J. The treatment of premenstrual syndrome with preparations of Vitex agnus castus: A systematic review and meta-analysis. Am. J. Obstet. Gynecol. 2017, 217, 150–166. [Google Scholar] [CrossRef]
- Janeš, D.; Glavač, N.K. (Eds.) Modern Cosmetics, Ingredients of Natural Origin, a Scientific View, 1st ed.; Širimo dobro besedo d.o.o.: Velenje, Slovenia, 2018; ISBN 978-961-94371-0-0. [Google Scholar]
- Oenothera biennis L. Plants of the World Online, Kew Science. Available online: http://www.plantsoftheworldonline.org/taxon/urn:lsid:ipni.org:names:172755-2 (accessed on 15 January 2021).
- Bayles, B.; Usatine, R. Evening primprose oil. Am. Fam. Phys. 2009, 80, 1405–1408. [Google Scholar]
- European Medicines Agency (EMA); Committee on Herbal Medicinal Products (HMPC). EMA/HMPC/753041/2017 European Union Herbal Monograph on Oenothera biennis L. or Oenothera lamarckiana L., Oleum; EMA: Amsterdam, The Netherlands; HMPC: London, UK, 2018; Volume 44, pp. 1–6. [Google Scholar]
- Cerin, A.; Collins, A.; And, B.L.; Eneroth, P. Hormonal and biochemical profiles of premenstrual syndrome: Treatment with essential fatty acids. Acta Obstet. Gynecol. Scand. 1993, 72, 337–343. [Google Scholar] [CrossRef]
- Horrobin, D.F. The role of essential fatty acids and prostaglandins in the premenstrual syndrome. J. Reprod. Med. 1983, 28, 465–468. [Google Scholar]
- Brush, M.G.; Watson, S.J.; Horrobin, D.F.; Manku, M.S. Abnormal essential fatty acid levels in plasma of women with premenstrual syndrome. Am. J. Obstet. Gynecol. 1984, 150, 363–366. [Google Scholar] [CrossRef]
- Puolakka, J.; Makarainen, L.; Viinikka, L.; Ylikorkala, O. Biochemical and clinical effects of treating the premenstrual syndrome with prostaglandin synthesis precursors. J. Reprod. Med. Obstet. Gynecol. 1985, 30, 149–153. [Google Scholar]
- Pye, J.K.; Mansel, R.E.; Hughes, L.E. Clinical experience of drug treatments for mastalgia. Lancet 1985, 326, 373–377. [Google Scholar] [CrossRef]
- Massil, H.Y.; O’Brien, P.M.S. Approach to the management of premenstrual syndrome. Clin. Obstet. Gynecol. 1987, 30, 443–452. [Google Scholar] [CrossRef]
- Pruthi, S.; Wahner-Roedler, D.L.; Torkelson, C.J.; Cha, S.S.; Thicke, L.A.; Hazelton, J.H.; Bauer, B.A. Vitamin E and Evening Primrose Oil for Management of Cyclical Mastalgia: A Randomized Pilot Study. Altern. Med. Rev. 2010, 15, 59–67. [Google Scholar]
- Mcfayden, I.J.; Forrest, A.P.; Chetty, U.; Raab, G. Cyclical breast pain—Some observations and the difficulties in treatment. Br. J. Clin. Pract. 1992, 46, 161–164. [Google Scholar]
- Blommers, J.; De Lange-de Klerk, E.S.M.; Kuik, D.J.; Bezemer, P.D.; Meijer, S. Evening primrose oil and fish oil for severe chronic mastalgia: A randomized, double-blind, controlled trial. Am. J. Obstet. Gynecol. 2002, 187, 1389–1394. [Google Scholar] [CrossRef] [PubMed]
- Kashani, L.; Saedi, N.; Akhondzadeh, S. Femicomfort in the treatment of premenstrual syndromes: A double-blind, randomized and placebo controlled trial. Iran. J. Psychiatry 2010, 5, 47–50. [Google Scholar] [PubMed]
- Kazemi, F.; Masoumi, S.Z.; Shayan, A.; Oshvandi, K. The Effect of Evening Primrose Oil Capsule on Hot Flashes and Night Sweats in Postmenopausal Women: A Single-Blind Randomized Controlled Trial. J. Menopausal Med. 2021, 27, 8. [Google Scholar] [CrossRef] [PubMed]
- Mehrpooya, M.; Rabiee, S.; Larki-Harchegani, A.; Fallahian, A.-M.; Moradi, A.; Ataei, S.; Javad, M.T. A comparative study on the effect of “black cohosh” and “evening primrose oil” on menopausal hot flashes. J. Educ. Health Promot. 2018, 7, 36. [Google Scholar] [PubMed]
- Cancelo Hidalgo, M.J.; Castelo-Branco, C.; Blumel, J.E.; Lanchares Pérez, J.L.; Alvarez De Los Heros, J.I. Effect of a compound containing isoflavones, primrose oil and vitamin E in two different doses on climacteric symptoms. J. Obstet. Gynaecol. 2006, 26, 344–347. [Google Scholar] [CrossRef] [PubMed]
- Khoo, S.K.; Munro, C.; Battistutta, D. Evening primrose oil and treatment of premenstrual syndrome. Med. J. Aust. 1990, 153, 189–192. [Google Scholar] [CrossRef] [PubMed]
- Collins, A.; Cerin, A.; Coleman, G.; Landgren, B.M. Essential fatty acids in the treatment of premenstrual syndrome. Obstet. Gynecol. 1993, 81, 93–98. [Google Scholar]
- Goyal, A.; Mansel, R.E. A randomized multicenter study of gamolenic acid (Efamast) with and without antioxidant vitamins and minerals in the management of mastalgia. Breast J. 2005, 11, 41–47. [Google Scholar] [CrossRef]
- Jaafarnejad, F.; Adibmoghaddam, E.; Emami, S.; Saki, A. Compare the effect of flaxseed, evening primrose oil and Vitamin E on duration of periodic breast pain. J. Educ. Health Promot. 2017, 6, 85. [Google Scholar]
- Chenoy, R.; Hussain, S.; Tayob, Y.; O’brien, P.M.S.; Moss, M.Y.; Morse, P.F. Effect of oral gamolenic acid from evening primrose oil on menopausal flushing. BMJ 1994, 308, 501–503. [Google Scholar] [CrossRef] [Green Version]
- Budeiri, D.; Li Wan Po, A.; Dornan, J.C. Is evening primrose oil of value in the treatment of premenstrual syndrome? Control. Clin. Trials 1996, 17, 60–68. [Google Scholar] [CrossRef]
- Low Dog, T. Menopause: A review of botanical dietary supplements. Am. J. Med. 2005, 118, 98–108. [Google Scholar] [CrossRef]
- Dante, G.; Facchinetti, F. Herbal treatments for alleviating premenstrual symptoms: A systematic review. J. Psychosom. Obstet. Gynecol. 2011, 32, 42–51. [Google Scholar] [CrossRef] [PubMed]
- Srivastava, A.; Mansel, R.E.; Arvind, N.; Prasad, K.; Dhar, A.; Chabra, A. Evidence-based management of Mastalgia: A meta-analysis of randomised trials. Breast 2007, 16, 503–512. [Google Scholar] [CrossRef] [PubMed]
- Stevinson, C.; Ernst, E. Complementary/alternative therapies for premenstrual syndrome: A systematic review of randomized controlled trials. Am. J. Obstet. Gynecol. 2001, 185, 227–235. [Google Scholar] [CrossRef]
- Pakzad, K.; Boucher, B.A.; Kreiger, N.; Cotterchio, M. The use of herbal and other non-vitamin, non mineral supplements among pre- and post-menopausal women in Ontario. Can. J. Public Health 2007, 98, 383–388. [Google Scholar] [CrossRef] [PubMed]
- Gentry-Maharaj, A.; Karpinskyj, C.; Glazer, C.; Burnell, M.; Ryan, A.; Fraser, L.; Lanceley, A.; Jacobs, I.; Hunter, M.S.; Menon, U. Use and perceived efficacy of complementary and alternative medicines after discontinuation of hormone therapy: A nested United Kingdom Collaborative Trial of Ovarian Cancer Screening cohort study. Menopause 2015, 22, 384–390. [Google Scholar] [CrossRef] [Green Version]
- Gartoulla, P.; Davis, S.R.; Worsley, R.; Bell, R.J. Use of complementary and alternative medicines for menopausal symptoms in Australian women aged 40–65 years. Med. J. Aust. 2015, 203, 146–153. [Google Scholar] [CrossRef]
- Girman, A.; Lee, R.; Kligler, B. An integrative medicine approach to premenstrual syndrome. Am. J. Obstet. Gynecol. 2003, 188, S56–S65. [Google Scholar] [CrossRef] [PubMed]
- European Medicines Agency (EMA); Committee on Herbal Medicinal Products (HMPC). EMA/HMPC/146220/2010 Assessment Report on Trigonella foenum-graecum L., Semen; EMA: Amsterdam, The Netherlands; HMPC: London, UK, 2010; Volume 44, pp. 1–42. [Google Scholar]
- Nagulapalli Venkata, K.C.; Swaroop, A.; Bagchi, D.; Bishayee, A. A small plant with big benefits: Fenugreek (Trigonella foenum-graecum Linn.) for disease prevention and health promotion. Mol. Nutr. Food Res. 2017, 61, 1600950. [Google Scholar] [CrossRef]
- Sreeja, S.; Anju, V.S.; Sreeja, S. In vitro estrogenic activities of fenugreek Trigonella foenum graecum seeds. Indian J. Med. Res. 2010, 131, 814–819. [Google Scholar]
- Shabbeer, S.; Sobolewski, M.; Anchoori, R.K.; Kachhap, S.; Davidson, N.; Carducci, M.A.; Khan, S.R. Fenugreek a naturally occurring edible spice as an anticancer agent. Cancer Biol. Ther. 2009, 8, 272–278. [Google Scholar] [CrossRef] [Green Version]
- Srinivasan, S.; Koduru, S.; Kumar, R.; Venguswamy, G.; Kyprianou, N.; Damodaran, C. Diosgenin targets Akt-mediated prosurvival signaling in human breast cancer cells. Int. J. Cancer 2009, 125, 961–967. [Google Scholar] [CrossRef]
- Rao, A.; Steels, E.; Beccaria, G.; Inder, W.J.; Vitetta, L. Influence of a Specialized Trigonella foenum-graecum Seed Extract (Libifem), on Testosterone, Estradiol and Sexual Function in Healthy Menstruating Women, a Randomised Placebo Controlled Study. Phyther. Res. 2015, 29, 1123–1130. [Google Scholar] [CrossRef] [PubMed]
- Younesy, S.; Amiraliakbari, S.; Esmaeili, S.; Alavimajd, H.; Nouraei, S. Effects of fenugreek seed on the severity and systemic symptoms of dysmenorrhea. J. Reprod. Infertil. 2014, 15, 41–48. [Google Scholar]
- Hakimi, S.; Mohammad Alizadeh, S.; Delazar, A.; Abbasalizadeh, F.; Bamdad Mogaddam, R.; Siiahi, M.R.; Mostafa Garabagi, P. Probable Effects of Fenugreek Seed on Hot Flash in Menopausal Women. J. Med. Plants 2006, 5, 9–14. [Google Scholar]
- Khanna, A.; John, F.; Das, S.; Thomas, J.; Rao, J.; Maliakel, B.; IM, K. Efficacy of a novel extract of fenugreek seeds in alleviating vasomotor symptoms and depression in perimenopausal women: A randomized, double-blinded, placebo-controlled study. J. Food Biochem. 2020, 44, e13507. [Google Scholar] [CrossRef]
- Thomas, J.V.; Rao, J.; John, F.; Begum, S.; Maliakel, B.; IM, K.; Khanna, A. Phytoestrogenic effect of fenugreek seed extract helps in ameliorating the leg pain and vasomotor symptoms in postmenopausal women: A randomized, double-blinded, placebo-controlled study. Pharm. Nutr. 2020, 14, 100209. [Google Scholar] [CrossRef]
- The Plant List: Search Results for “Humulus”. Available online: http://www.theplantlist.org/tpl1.1/search?q=Humulus (accessed on 26 August 2021).
- Bocquet, L.; Sahpaz, S.; Hilbert, J.L.; Rambaud, C.; Rivière, C. Humulus lupulus L., a very popular beer ingredient and medicinal plant: Overview of its phytochemistry, its bioactivity, and its biotechnology. Phytochem. Rev. 2018, 17, 1047–1090. [Google Scholar] [CrossRef]
- Stevens, J.F.; Taylor, A.W.; Deinzer, M.L. Quantitative analysis of xanthohumol and related prenylflavonoids in hops and beer by liquid chromatography-tandem mass spectrometry. J. Chromatogr. A 1999, 832, 97–107. [Google Scholar] [CrossRef]
- Stevens, J.F.; Ivancic, M.; Hsu, V.L.; Deinzer, M.L. Prenylflavonoids from Humulus lupulus. Phytochemistry 1997, 44, 1575–1585. [Google Scholar] [CrossRef]
- Chadwiek, L.R.; Nikolic, D.; Burdette, J.E.; Overk, C.R.; Bolton, J.L.; Van Breemen, R.B.; Fröhlich, R.; Fong, H.H.S.; Farnsworth, N.R.; Pauli, G.F. Estrogens and congeners from spent hops (Humulus lupulus). J. Nat. Prod. 2004, 67, 2024–2032. [Google Scholar] [CrossRef]
- European Medicines Agency (EMA); Committee on Herbal Medicinal Products (HMPC). EMA/HMPC/682384/2013 Community Herbal Monograph on Humulus lupulus L., Flos; EMA: Amsterdam, The Netherlands; HMPC: London, UK, 2014; Volume 44, pp. 1–7. [Google Scholar]
- Milligan, S.R.; Kalita, J.C.; Heyerick, A.; Rong, H.; De Cooman, L.; De Keukeleire, D. Identification of a potent phytoestrogen in hops (Humulus lupulus L.) and beer. J. Clin. Endocrinol. Metab. 1999, 84, 2249–2252. [Google Scholar] [CrossRef] [PubMed]
- Koch, W.; Heim, G. Östrogene Hormone in Hopfen und Bier. Med. Wchnschr. 1953, 95, 845. [Google Scholar]
- Heyerick, A.; Vervarcke, S.; Depypere, H.; Bracke, M.; Keukeleire, D. De A first prospective, randomized, double-blind, placebo-controlled study on the use of a standardized hop extract to alleviate menopausal discomforts. Maturitas 2006, 54, 164–175. [Google Scholar] [CrossRef] [PubMed]
- Erkkola, R.; Vervarcke, S.; Vansteelandt, S.; Rompotti, P.; De Keukeleire, D.; Heyerick, A. A randomized, double-blind, placebo-controlled, cross-over pilot study on the use of a standardized hop extract to alleviate menopausal discomforts. Phytomedicine 2010, 17, 389–396. [Google Scholar] [CrossRef]
- Aghamiri, V.; Mirghafourvand, M.; Mohammad-Alizadeh-Charandabi, S.; Nazemiyeh, H. The effect of Hop (Humulus lupulus L.) on early menopausal symptoms and hot flashes: A randomized placebo-controlled trial. Complement. Ther. Clin. Pract. 2016, 23, 130–135. [Google Scholar] [CrossRef] [PubMed]
- Ferk, F.; Mišík, M.; Nersesyan, A.; Pichler, C.; Jäger, W.; Szekeres, T.; Marculescu, R.; Poulsen, H.E.; Henriksen, T.; Bono, R.; et al. Impact of xanthohumol (a prenylated flavonoid from hops) on DNA stability and other health-related biochemical parameters: Results of human intervention trials. Mol. Nutr. Food Res. 2016, 60, 773–786. [Google Scholar] [CrossRef]
- Possemiers, S.; Bolca, S.; Grootaert, C.; Heyerick, A.; Decroos, K.; Dhooge, W.; De Keukeleire, D.; Rabot, S.; Verstraete, W.; Van De Wiele, T. The prenylflavonoid isoxanthohumol from hops (Humulus lupulus L.) is activated into the potent phytoestrogen 8-prenylnaringenin in vitro and in the human intestine. J. Nutr. 2006, 136, 1862–1867. [Google Scholar] [CrossRef] [Green Version]
- Legette, L.; Karnpracha, C.; Reed, R.L.; Choi, J.; Bobe, G.; Christensen, J.M.; Rodriguez-Proteau, R.; Purnell, J.Q.; Stevens, J.F. Human pharmacokinetics of xanthohumol, an antihyperglycemic flavonoid from hops. Mol. Nutr. Food Res. 2014, 58, 248–255. [Google Scholar] [CrossRef]
- van Breemen, R.B.; Yuan, Y.; Banuvar, S.; Shulman, L.P.; Qiu, X.; Ramos Alvarenga, R.F.; Chen, S.N.; Dietz, B.M.; Bolton, J.L.; Pauli, G.F.; et al. Pharmacokinetics of prenylated hop phenols in women following oral administration of a standardized extract of hops. Mol. Nutr. Food Res. 2014, 58, 1962–1969. [Google Scholar] [CrossRef] [Green Version]
- Bolca, S.; Li, J.; Nikolic, D.; Roche, N.; Blondeel, P.; Possemiers, S.; De Keukeleire, D.; Bracke, M.; Heyerick, A.; Van Breemen, R.B.; et al. Disposition of hop prenylflavonoids in human breast tissue. Mol. Nutr. Food Res. 2010, 54, S284–S294. [Google Scholar] [CrossRef] [Green Version]
- Trifolium pratense L. Plants of the World Online, Kew Science. Available online: http://www.plantsoftheworldonline.org/taxon/urn:lsid:ipni.org:names:523575-1 (accessed on 10 September 2021).
- Trifolium Pratense (Red Clover): Go Botany. Available online: https://gobotany.nativeplanttrust.org/species/trifolium/pratense/ (accessed on 10 September 2021).
- Lemežienė, N.; Padarauskas, A.; Butkutė, B.; Cesevičienė, J.; Taujenis, L.; Norkevičienė, E.; Mikaliūnienė, J. The concentration of isoflavones in red clover (Trifolium pratense L.) at flowering stage. Zemdirbyste 2015, 102, 443–448. [Google Scholar] [CrossRef] [Green Version]
- Nelsen, J.; Ulbricht, C.; Barrette, E.P.; Mac, D.S.; Tsouronis, C.; Rogers, A.; Basch, S.; Hashmi, S.; Bent, S.; Basch, E. Red Clover (Trifolium pratense) Monograph. J. Herb. Pharmacother. 2002, 2, 49–72. [Google Scholar]
- Messina, M.; Mejia, S.B.; Cassidy, A.; Duncan, A.; Kurzer, M.; Nagato, C.; Ronis, M.; Rowland, I.; Sievenpiper, J.; Barnes, S. Neither soyfoods nor isoflavones warrant classification as endocrine disruptors: A technical review of the observational and clinical data. Crit. Rev. Food Sci. Nutr. 2021, 1–62. [Google Scholar] [CrossRef]
- European Medicines Agency (EMA); Committee on Herbal Medicinal Products (HMPC). EMA/HMPC/150848/2015, Corr. European Union Herbal Monograph on Valeriana officinalis L., Flos; EMA: Amsterdam, The Netherlands; HMPC: London, UK, 2016; Volume 31, pp. 1–9. [Google Scholar]
- European Medicines Agency (EMA); Committee on Herbal Medicinal Products (HMPC). EMA/HMPC/150846/2015. Assessment report on Valeriana officinalis L., Radix and Valeriana officinalis L., Aetheroleum; EMA: Amsterdam, The Netherlands; HMPC: London, UK, 2015; Volume 31, pp. 1–71. [Google Scholar]
- Usmanghani, K.; Saeed, A.; Muhammad Tanweer, A. Indusyunic Medicine: Traditional Medicine of Herbal Animal and Mineral Origin in Pakistan; Department of Pharmacognosy, Faculty of Pharmacy, University of Karachi: Karachi, Pakistan, 1997. [Google Scholar]
- Santos, M.S.; Ferreira, F.; Cunha, A.P.; Carvalho, A.P.; Macedo, T. An aqueous extract of valerian influences the transport of GABA in synaptosomes. Planta Med. 1994, 60, 278–279. [Google Scholar] [CrossRef] [PubMed]
- Ortiz, J.G.; Nieves-Natal, J.; Chavez, P. Effects of Valeriana Officinalis extracts on [3H]flunitrazepam binding, synaptosomal [3H]GABA uptake, and hippocampal [3H]GABA release. Neurochem. Res. 1999, 24, 1373–1378. [Google Scholar] [CrossRef]
- Santos, M.S.; Ferreira, F.; Cunha, A.P.; Carvalho, A.P.; Ribeiro, C.F.; Macedo, T. Synaptosomal GABA release as influenced by valerian root extract--involvement of the GABA carrier. Arch. Int. Pharmacodyn. Ther. 1994, 327, 220–231. [Google Scholar] [PubMed]
- Cavades, C.; Araújo, I.; Cotrim, M.D.; Amaral, T.; Cunha, A.P.; Macedo, T.; Ribeiro, C.F. In vitro study on the interaction of Valeriana officinalis L. extracts and their amino acids on GABAA receptor in rat brain. Arzneimittelforschung 1995, 45, 753–755. [Google Scholar]
- Park, J.Y.; Lee, Y.; Lee, H.J.; Kwon, Y.S.; Chun, W. In silico screening of GABA aminotransferase inhibitors from the constituents of Valeriana officinalis by molecular docking and molecular dynamics simulation study. J. Mol. Model. 2020, 26, 228. [Google Scholar] [CrossRef] [PubMed]
- Taavoni, S.; Ekbatani, N.; Kashaniyan, M.; Haghani, H. Effect of valerian on sleep quality in postmenopausal women: A randomized placebo-controlled clinical trial. Menopause 2011, 18, 951–955. [Google Scholar] [CrossRef]
- Mirabi, P.; Mojab, F. The effects of valerian root on hot flashes in menopausal women. Iran. J. Pharm. Res. 2013, 12, 217–222. [Google Scholar] [PubMed]
- Jokar, A.; Kargosha, A.; Akarzadeh, M.; Asadi, N.; Setoudeh, Z. Comparing the influence of relaxation training and consumption of valerian on insomnia of menopause women: A randomized clinical trial. Afr. J. Tradit. Complement. Altern. Med. 2016, 13, 40–44. [Google Scholar] [CrossRef] [Green Version]
- Kazemian, A.; Parvin, N.; Raisi Dehkordi, Z.; Rafieian -Kopaei, M. The Effect of Valerian on the Anxiety and Depression Symptoms of the Menopause in Women Referred to Shahrekord Medical Centers. J. Med. Plants 2017, 16, 94–101. [Google Scholar]
- Jenabi, E.; Shobeiri, F.; Hazavehei, S.M.M.; Roshanaei, G. The effect of Valerian on the severity and frequency of hot flashes: A triple-blind randomized clinical trial. Women Health 2018, 58, 297–304. [Google Scholar] [CrossRef]
- Glycine max subsp. soja (Siebold & Zucc.) H.Ohashi. Plants of the World Online, Kew Science. Available online: http://www.plantsoftheworldonline.org/taxon/urn:lsid:ipni.org:names:920989-1 (accessed on 21 August 2021).
- Wang, K.J.; Li, X.H.; Zhang, J.J.; Chen, H.; Zhang, Z.L.; Yu, G.D. Natural introgression from cultivated soybean (Glycine max) into wild soybean (Glycine soja) with the implications for origin of populations of semi-wild type and for biosafety of wild species in China. Genet. Resour. Crop Evol. 2010, 57, 747–761. [Google Scholar] [CrossRef]
- Kuroda, Y.; Kaga, A.; Tomooka, N.; Yano, H.; Takada, Y.; Kato, S.; Vaughan, D. QTL affecting fitness of hybrids between wild and cultivated soybeans in experimental fields. Ecol. Evol. 2013, 3, 2150–2168. [Google Scholar] [CrossRef]
- Xu, Z.; Ren, T.; Marowa, P.; You, X.; Lu, X.; Li, Y.; Zhang, C. Establishment of a Cultivation Mode of Glycine soja, the Bridge of Phytoremediation and Industrial Utilization. Agronomy 2020, 10, 595. [Google Scholar] [CrossRef] [Green Version]
- Nawaz, M.A.; Lin, X.; Chan, T.F.; Ham, J.; Shin, T.S.; Ercisli, S.; Golokhvast, K.S.; Lam, H.M.; Chung, G. Korean wild soybeans (Glycine soja sieb and zucc.): Geographic distribution and germplasm conservation. Agronomy 2020, 10, 214. [Google Scholar] [CrossRef] [Green Version]
- Murphy, P.A.; Barua, K.; Hauck, C.C. Solvent extraction selection in the determination of isoflavones in soy foods. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 2002, 777, 129–138. [Google Scholar] [CrossRef]
- European Medicines Agency (EMA); Committee on Herbal Medicinal Products (HMPC). EMA/HMPC/220598/2016. Assessment Report on Glycine max (L.) Merr., Lecithinum; EMA: Amsterdam, The Netherlands; HMPC: London, UK, 2017; Volume 31, pp. 2–27. [Google Scholar]
- Izumi, T.; Piskula, M.K.; Osawa, S.; Obata, A.; Tobe, K.; Saito, M.; Kataoka, S.; Kubota, Y.; Kikuchi, M. Soy isoflavone aglycones are absorbed faster and in higher amounts than their glucosides in humans. J. Nutr. 2000, 130, 1695–1699. [Google Scholar] [CrossRef] [Green Version]
- European Food Safety Authority (EFSA). Risk assessment for peri- and post-menopausal women taking food supplements containing isolated isoflavones. EFSA J. 2015, 13, 4246. [Google Scholar] [CrossRef] [Green Version]
- Gramec Skledar, D.; Tvrdý, V.; Kenda, M.; Zega, A.; Pour, M.; Horký, P.; Mladěnka, P.; Sollner Dolenc, M.; Peterlin Mašič, L. Applicability of the OECD 455 in-vitro assay for determination of hERa agonistic activity of isoflavonoids. Toxicol. Appl. Pharmacol. 2020, 386, 114831. [Google Scholar] [CrossRef]
- Messina, M. Soy and health update: Evaluation of the clinical and epidemiologic literature. Nutrients 2016, 8, 754. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Taku, K.; Melby, M.K.; Kronenberg, F.; Kurzer, M.S.; Messina, M. Extracted or synthesized soybean isoflavones reduce menopausal hot flash frequency and severity: Systematic review and meta-analysis of randomized controlled trials. Menopause 2012, 19, 776–790. [Google Scholar] [CrossRef]
- Faure, E.D.; Chantre, P.; Mares, P. Effects of a standardized soy extract on hot flushes: A multicenter, double-blind, randomized, placebo-controlled study. Menopause 2002, 9, 329–334. [Google Scholar] [CrossRef] [Green Version]
- Stanosz, S.; Puk, E.; Grobelny, W.; Stanosz, M.; Kazikowska, A. Evaluation of the efficacy and tolerance of Soyfem in women in the early menopausal period. Prz. Menopauzalny 2006, 5, 182–190. [Google Scholar]
- Messina, M.; Venter, C. Recent Surveys on Food Allergy Prevalence. Nutr. Today 2020, 55, 22–29. [Google Scholar] [CrossRef]
- Katz, Y.; Gutierrez-Castrellon, P.; González, M.G.; Rivas, R.; Lee, B.W.; Alarcon, P. A comprehensive review of sensitization and allergy to soy-based products. Clin. Rev. Allergy Immunol. 2014, 46, 272–281. [Google Scholar] [CrossRef]
Plant Species, Drug Part | Active Compounds | Biological Activities/Supposed Mechanism of Action |
---|---|---|
Black cohosh (Cimicifuga racemosa) rhizome | Phenolic compounds (ferulic acid, isoferulic acid and caffeic acid derivatives, cycloartane triterpene glycosides (actein, 26-deoxyactein, cimicifugoside)) and phenylpropanoids, possibly phytoestrogenic flavonoid formononetin, Nω-methylserotonin, 23-O-acetylshengmanol-3-O-d-xylopyranoside [15,19,20] | |
Chaste tree (Vitex agnus-castus) fruit | Volatile compounds (essential oil), flavonoids and other phenolic compounds, iridoids, ketosteroids, chastol and epichastol diterpenoids [30,31,32,33] Methoxylated flavonol casticin, (also known as vitexicarpin) [34] | |
Evening primrose (Oenothera biennis) seed | 20% of oil (triglycerides) containing linoleic acid, γ-linolenic acid, palmitic acid, stearic acid, oleic acid, α-linolenic acid, unsaponifiable matter [34,58] |
|
Fenugreek (Trigonella foenum-graecum) seed | Polysaccharides (24–25% galactomannans), 0.016% essential oil, secondary metabolites (protoalkaloids, trigonelline, choline), 0.6–1.7% saponins (from diosgenin, yamogenin, tigogenin, and others), sterols (β-sitosterol), and flavonoids (orientin, isoorientin, isovitexin) [89] | |
Hops (Humulus lupulus) inflorescence | Essential oil (constituents: β-myrcene, β-caryophyllene, α-humulene, β-farnesene, α-selinene, β-selinene, humulene epoxides, β-bisabolol, 2-methyl-3-buten-2-ol, a.s.o.), prenylated acylphloroglucinols (α-acids: humulone, its derivatives, and β-acids: lupulones), prenylated flavanones (isoxanthohumol, 6-prenylnaringenin, 8-prenylnaringenin), chalcones (xanthohumol, desmethylxanthohumol), triterpenes, flavonols, and tannins [100] | |
Red clover (Trifolium pratense) stem, leaf, flower | Isoflavones formononetin, biochanin A, daidzein and genistein, glycitein and prunetin [8,117] |
|
Valerian (Valeriana officinalis) rhizome, roots, stolons | Isovaleric acid and didrovaltrate [127] |
|
Soybean (Glycine max and Glycine soja) seed | Saponins and isoflavones (e.g., daidzein, 6-hydroxy-daidzein, daidzein glycosides, genistein, genistein glycosides, glycitein, and glycitein glycosides), trypsin inhibitors, and twice the amount of α-linolenic acid as domesticated soybean [135] Glycoside forms of the three aglycons may be β-glucosides, 6″-O-malonyl-glucosides and 6″-O-acetyl-glucosides [138] |
|
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Kenda, M.; Glavač, N.K.; Nagy, M.; Sollner Dolenc, M.; on behalf of the OEMONOM. Herbal Products Used in Menopause and for Gynecological Disorders. Molecules 2021, 26, 7421. https://doi.org/10.3390/molecules26247421
Kenda M, Glavač NK, Nagy M, Sollner Dolenc M, on behalf of the OEMONOM. Herbal Products Used in Menopause and for Gynecological Disorders. Molecules. 2021; 26(24):7421. https://doi.org/10.3390/molecules26247421
Chicago/Turabian StyleKenda, Maša, Nina Kočevar Glavač, Milan Nagy, Marija Sollner Dolenc, and on behalf of the OEMONOM. 2021. "Herbal Products Used in Menopause and for Gynecological Disorders" Molecules 26, no. 24: 7421. https://doi.org/10.3390/molecules26247421
APA StyleKenda, M., Glavač, N. K., Nagy, M., Sollner Dolenc, M., & on behalf of the OEMONOM. (2021). Herbal Products Used in Menopause and for Gynecological Disorders. Molecules, 26(24), 7421. https://doi.org/10.3390/molecules26247421