Gynecological Herbs

Summary

Gynecological Herbs

introduction:
Traditionally, a large number of different herbs have been used to affect different aspects of the activity of the female reproductive tract. Historically, there is a legacy of confusion and little agreement even among contemporary authorities about the precise meaning of different designations and classifications of herbs used in gynecology. For a review of author discrepancies see The Phytoestrogen Debate by Peggy Wilbur, and for a historical review of herbs used in gynecological conditions see A Comparative Review of Eclectic Female Regulators by Francis Brinker. Endocrine-like activities of herbs used for gynecological purposes do not necessarily correspond with traditional terminology which is therefore reviewed briefly below. Better general surveys of herbs used gynecologically in modern herbal therapeutics may be found in books by herbalists Amanda McQuade-Crawford and Ruth Trickey.

From the perspective of drug-herb interactions, herbs with identifiable hormone-like activities on the hypothalamic-pituitary-gonadal axis (HPA) are considered in Interactions™, although detailed studies and reports of interactions between pharmaceutical drugs and these agents are not available.
(Brinker F. Brit J Phytotherapy 1997;4,3:123-145; McQuade-Crawford A. 1997; Trickey R. 1998; Wilbur P. Eur J Herbal Med 1996 2.2:20-26, and 1996 2.3:19-26.)

food/herb group affecting drug performance: Oral Contraceptives

• mechanism: Phytoestrogenic constituents of foods and medicinal herbs may interact with steroid sex hormone metabolism, and synergize with exogenous steroid hormones in ERT (Estrogen Replacement Therapy), HRT (Hormone Replacement Therapy).

• herbal concerns: Despite lack of scientific evidence of adverse interactions, prudence suggests that herbs possessing direct endocrinological effects on the female reproductive tract should be avoided during treatment with ERT (Estrogen Replacement Therapy), HRT (Hormone Replacement Therapy), or GnRH (Gonadotrophic Releasing Hormone) inhibitors.

• herbal support: Cimicifuga racemosa (Black Cohosh) has been used to support withdrawal from HRT and ERT and to adjunctively treat symptoms of menopause.


herbs affecting Hypothalamic-Pituitary Axis (HPA):

• phytoestrogens: Phytoestrogens may be defined as plant constituents possessing the ability to mimic the biological effects of beta-estradiol in laboratory tests by their ability to bind to the nuclear estrogen receptor, activate transcriptional response and to promote growth of estrogen dependent MCF7 cells in culture. Phytoestrogenic activity is found among the following five naturally occurring chemical compound groupings which are widely distributed among medicinal and food plants:
• Isoflavonoids (e.g., formononetin, daidzein, genistein, coumestrol, biochanin A)
• Sterols (e.g., beta-sitosterol, stigmasterol)
• Saponins (e.g., diosgenin),
• Lignans (e.g., enterolactone),
• Essential oils (Clary sage, Fennel)
Isoflavonoid phytoestrogenic constituents are nutritionally available in plants from the Fabaceae (bean) family, particularly Glycine max (Soybean). Among medicinal plants, the most important phytoestrogenic plant in common therapeutic use is Cimicifuga racemosa (Black Cohosh).

Comprehensive lists of plants containing phytoestrogenic constituents can be found in various sources such as James Duke's Handbook of Phytochemical Constituents of GRAS Herbs and Other Economical Plants or the related database of the Agricultural Research Service - Phytochemical and Ethnobotanical Databases (http://www.ars-grin.gov/duke/) and the NAPRALERT database.
(Duke JA.1994; Miksicek R. Mol Pharmacol, 44(1):37-43, 1993.)

In clinical practice, it has long been known that phytoestrogenic medicinal herbs often have both estrogenic and anti-estrogenic actions. This variability in action remains to be elucidated in terms of potency of phytoestrogenic constituents, balance of agonistic and antagonistic tendencies and compounds, short and long term effects, as well as the problem of different methodological approaches used to identify estrogenicity. The functional endocrinological status of the consumer/patient adds to this complexity, although this is well understood by clinicians experienced in the use of these agents. For example, Cimicifuga racemosa (Black Cohosh) may be used to help correct estrogen dominance in pre-menopausal women yet supports estrogenic activity in post-menopausal women.

Herbalist David Hoffmann has recently reviewed developments in phytoestrogen research and considers that the FDA's National Center for Toxicological Research has identified the importance and need for further research in clarifying the roles of bioavailable estrogenic substances in three respects: estrogen agonism, estrogen antagonism, and endocrine disruption (particularly disruption of the development of secondary sexual characteristics and the reduction of sperm counts). The toxicology approach emphasizes the role of xenoestrogens rather then phytoestrogens, but nutritional phytoestrogens are included within the broad scope of future research and possible regulation. At present, only general conclusions can be made about the role of phytoestrogens which (after Hoffman D.) could be summarized:

1. A number of diverse plant constituents contribute significantly to human estrogen exposure at dietary levels.
2. Nutritionally available estrogenic substances can have a significant role in estrogen metabolism.
3. Biological activity of phytoestrogens extends beyond simple estrogen receptor activity to effects on cellular differentiation, proliferation, angiogenesis, enzyme inhibition, growth factor action and other effects which constitute protective activity against cancer.
4. Dietary incorporation of isoflavone rich foods may contribute to the reduction of risk of cancer; in particular, the majority of studies on soy isoflavones have confirmed significant anti-cancer effects.

• aromatase modifiers: Some flavone and isoflavone constituents can inhibit aromatase. Aromatase is a P450 enzyme that catalyzes the formation of estrogens from androgens in many tissues. The activity is greater for flavone constituents rather than the isoflavone constituents, and while this may account for part of the anti-estrogenic activity of some flavonoid phytoestrogens, other herbs are known to reverse low aromatase activity, the most studied being Paeonia lactiflora (White peony). In vitro studies have shown the aromatase action of Paeonia to be due to the monoterpene glycoside, paeoniflorin.
(Chen S, et al. J Steroid Biochem Mol Biol 61,3-6:107-115,1997; Takeuchi T, et al. Am J Chin Med 1991;18:73-78.)

See also the following: Nutrients: Flavonoids, Quercitin and Grapefruit Juice

• direct pituitary agents: While Cimicifuga racemosa and soy products can influence pituitary action by peripheral modulation of LH and FSH via estrogenic effects, other herbs act directly upon the pituitary to modify prolactin, FSH and LH levels. The best known example is Vitex agnus-castus (Chasteberry). Animal studies have demonstrated Vitex inhibits prolactin levels in vitro and in vivo by binding to dopamine D2 receptors in the pituitary. Human studies have shown increase in progesterone levels in corpus luteum insufficiency during Vitex administration.

• oxytocics: Several plant constituents have been shown to have oxytocic activity, notably caulosaponin and caulophyllosaponin from Caulophyllum thalictroides (Blue Cohosh) which is classified as a traditional emmenagogue. Other oxytocic compounds include sparteine in Cytisus scoparius (Scotch Broom), and quinine from Cinchona species.

• commentary: Wild Yam and "Natural Progesterone": There has been some confusion concerning products containing Dioscorea villosa (Mexican Wild Yam) that claim to boost endogenous progesterone levels, or to be a form of "natural progesterone". To add to the confusion, some topical preparations actually contain both Dioscorea extract and pharmaceutical progesterone. The following points should be noted:
• The natural steroidal compound diosgenin is in fact estrogenic, not progesteronic.
• Diosgenin has been used as a starter compound in the laboratory synthesis of progesterone patented by Marker in the late 1940's known as the Marker Degradation Process.
• Homologous metabolic pathways do not exist humans, and diosgenin is therefore not a "precursor" for endogenous progesterone synthesis.
(Brinker F. Brit J Phytotherapy 1997;4,3:123-145; Wilbur P. Eur J Herbal Med 1996 2.2:20-26, and 1996 2.3:19-26.)

terminology: herbs directly affecting the uterus:
• Uterine Tonics: Herbs that re-establish normal tone of the uterine muscle and improve overall strength of the organ. Examples: Rubus idaeus (Red raspberry leaf), Angelica sinensis (Dong Quai), Chamaelerium luteum (Helonias, False Unicorn root).
• Uterine Spasmolytics: Herbs that reduce the rate and amplitude of uterine contractions. Examples: Viburnum opulus (Cramp bark), Viburnum prunifolium (Black Haw), Ligusticum wallichii (Chuang Xiong).
• Uterine Emmenagogues: Traditionally defined as herbs that accelerate delayed menses. More accurately, herbs that stimulate uterine contractions and hence may increase expulsive activity of the uterus.These have also been described as abortifacients. Examples: Ruta graveolens (Rue), Artemisia vulgaris (Mugwort), Mentha pulegium (Pennyroyal).
• Uterine Astringents: Herbs that have a vasoconstrictive action on the endometrial circulation. Examples: Achillea millefolium (Yarrow), Alchemilla vulgaris (Lady's mantle), Trillium erectum (Beth root), Capsella bursa-pastoris (Shepherd's Purse).



Herbs

Herbs listed in this section are compiled and edited from electronic databases including Professor Norman Farnsworth's NAPRALERT database at University of Chicago, Illinois, and Dr. James Duke's Phytochemical and Ethnobotanical Databases at the Agricultural Research Service. Textual sources include Michael Moore's Herbal/Medical Contraindications and Francis Brinker's Herb Contraindications and Drug Interactions.
(Moore M. 1995; Brinker F. 1998.)

Plant activities may be based upon widely different assay methods, and may be laboratory, in vitro, in vivo, or human studies. Constituent data is not quantified. Estrogenic constituents are very widely distributed and the following lists are limited to more common medicinal and edible plants. For principal herbs in common therapeutic gynecological use see Summary section of this Herb Group in Interactions™.

Herbs with HPA (Hypothalamic-Pituitary Axis) activty: Oxytocic synergists:
• Asclepias asperula (Immortal)
• Capsella bursa-pastoris (Shepherd's Purse)
• Cinchona spp. (Cinchona bark) *
• Claviceps purpurea (Ergot of Rye) *
• Cytisus scoparius (Scotch Broom)
• Gossypium spp.(Cotton root Bark)
• Leonurus cardiaca (Motherwort)
• Myristica fragrans (Nutmeg)
• Petroselinum crispum (Parsely)
• Senecio aureus (Life Root) *
• Stachys betonica (Wood Betony)

Herbs with HPA (Hypothalamic-Pituitary Axis) activity: Prolactin inhibitors:
• Glycyrrhiza glabra (Licorice root)
• Paeonia lactiflora (Peony)
• Rehmannia glutinosa (Chinese Foxglove)
• Vitex agnus-castus (Chasteberry)
• Chinese herbal formula: Rehmannia Eight
• Chinese herbal formula: Paeonia and Glycyrrhiza

Herbs with HPA (Hypothalamic-Pituitary Axis) activity: FSH/LH modifiers:
• Cimicifuga racemosa (Black Cohosh)
• Tripterygium wilfordii (Lei Gong Teng) *
• Vitex agnus-castus (Chasteberry)

Herbs with HPA (Hypothalamic-Pituitary Axis) activity: Progestagenics:
• Alchemilla vulgaris (Ladie's mantle)
• Angelica sinensis (Dong Quai)
• Areca catechu (Betel nut)
• Ceanothus americanus (Red Root)
• Vitex agnus-castus (Chasteberry)

Chinese herbal formula: including:
• Angelica sinensis (Dong Quai)
• Astragalus membranaceus (Astragalus)
• Gardenia jasminoides (Zhi zi)
• Leonurus heterophyllus (Chinese Motherwort)
• Panax notoginseng (Pseudoginseng)
• Rubia cordifolia (Madder)
• Scutellaria baicalensis (Baical Skullcap)

Common phytoestrogenic food/herbs containing: Coumestrol
• Brassica spp. (Brussels Sprouts, Cabbage)
• Glycine max (Soybean)
• Medicago sativa (Alfalfa)
• Pisum sativum (Pea)
• Trifolium pratense (Red Clover)
• Vigna radiata (Mungbean)

Common phytoestrogenic food/herbs containing: Biochanin A:
• Baptisia tinctoria (Wild Indigo)
• Medicago sativa (Alfalfa)
• Sophora japonica (Japanese Pagoda Tree)
• Trifolium pratense (Red Clover)
• Vigna radiata (Mungbean)

Common phytoestrogenic food/herbs containing: Daidzein:
• Glycine max (Soybean)
• Phaseolus coccineus (Scarlet Runner Bean)
• Pueraria spp. (Kudzu; Pueraria)
• Trifolium pratense (Red Clover)
• Vigna radiata (Mungbean)

Common phytoestrogenic food/herbs containing: Formononetin:
• Astragalus membranaceus (Astragalus)
• Cimicifuga racemosa (Black Cohosh)
• Glycyrrhiza glabra (Licorice root)
• Medicago sativa (Alfalfa)
• Pueraria spp. (Kudzu; Pueraria)
• Trifolium pratense (Red Clover)
• Vigna radiata (Mungbean)

Common phytoestrogenic food/herbs containing: Genistein:
• Baptisia tinctoria (Wild Indigo)
• Cytisus scoparius (Scotch Broom)
• Glycine max (Soybean)
• Glycyrrhiza glabra (Licorice root)
• Medicago sativa (Alfalfa)
• Pueraria spp. (Kudzu; Pueraria)
• Sophora japonica (Japanese Pagoda Tree)
• Trifolium pratense (Red Clover)
• Vigna radiata (Mungbean)

Common phytoestrogenic food/herbs containing: Beta-Sitosterol:
• Achillea millefolium (Yarrow)
• Allium cepa (Onion)
• Allium sativum (Garlic)
• Aloe vera (Aloe)
• Anethum graveolens (Dill)
• Angelica archangelica (Angelica)
• Angelica sinensis (Dong Quai)
• Arctostaphylos uva-ursi (Bearberry)
• Arnica montana (Arnica)
• Artemisia annua (Sweet Annie)
• Artemisia dracunculus (Tarragon)
• Artemisia vulgaris (Mugwort)
• Asarum canadense (Wild Ginger)
• Asclepias syriaca (Milkweed)
• Aspidosperma quebracho-blanco (Quebracho)
• Astragalus membranaceus (Astragalus)
• Avena sativa (Oats)
• Calendula officinalis (Marigold)
• Capsella bursa-pastoris (Shepherd's Purse)
• Capsicum annuum (Chili Pepper)
• Centaurium erythraea (Centaury)
• Centella asiatica (Gotu Kola)
• Chimaphila umbellata (Pipsissewa)
• Cnicus benedictus (Blessed Thistle)
• Commiphora myrrha (Myrrh)
• Crataegus spp. (Hawthorn)
• Cucurbita pepo (Pumpkin)
• Cytisus scoparius (Scotch Broom)
• Daucus carota (Wild Carrot)
• Echinacea spp. (Echinacea)
• Elettaria cardamomum (Cardamom)
• Eleutherococcus senticosus (Siberian Ginseng)
• Equisetum arvense (Horsetail )
• Fagopyrum esculentum (Buckwheat)
• Foeniculum vulgare (Fennel)
• Fucus vesiculosus (Bladderwrack)
• Glycine max (Soybean)
• Glycyrrhiza glabra (Licorice root)
• Gossypium spp. (Cotton)
• Hordeum vulgare (Barley)
• Humulus lupulus (Hops)
• Hyssopus officinalis (Hyssop)
• Inula helenium (Elecampane)
• Lactuca virosa (Bitter Lettuce)
• Liquidambar orientalis (Oriental Styrax)
• Marrubium vulgare (Horehound)
• Medicago sativa (Alfalfa)
• Melilotus officinalis (Melilot)
• Melissa officinalis (Lemon Balm)
• Mentha spicata (Spearmint)
• Nicotiana tabacum (Tobacco)
• Ocimum basilicum (Basil)
• Oenothera biennis (Evening Primrose)
• Paeonia lactiflora (Peony)
• Panax ginseng (Chinese Ginseng, Korean Ginseng)
• Panax quinquefolius (American Ginseng)
• Pisum sativum (Pea)
• Plantago psyllium (Psyllium seed)
• Ptychopetalum olacoides (Muira Puama)
• Punica granatum (Pomegranate)
• Rehmannia glutinosa (Chinese Foxglove)
• Rosmarinus officinalis (Rosemary)
• Salvia officinalis (Sage)
• Salvia sclarea (Clary Sage)
• Sambucus nigra (Elderflower)
• Sassafras albidum (Sassafras)
• Scutellaria baicalensis (Baikal Skullcap)
• Serenoa repens (Saw Palmetto)
• Smilax spp. (Sarsaparilla)
• Solanum dulcamara (Bitter Nightshade)
• Sophora japonica (Japanese Pagoda Tree)
• Taraxacum officinale ( Dandelion)
• Theobroma cacao (Cacao)
• Tribulus terrestris (Puncture-vine)
• Trifolium pratense (Red Clover)
• Trigonella foenum-graecum (Fenugreek)
• Turnera diffusa (Damiana)
• Urginea maritima (Squill)
• Valeriana officinalis (Valerian)
• Verbascum thapsus (Mullein)
• Viburnum opulus (Crampbark)
• Vinca minor (Periwinkle)
• Viola odorata (Sweet Violet)
• Vitis vinifera (Wine Grape)
• Withania somnifera (Ashwagandha)
• Zea mays (Corn silk)
• Zingiber officinale (Ginger)

Common phytoestrogenic food/herbs containing: Diosgenin:
• Agave sisalana (Mescal)
• Aletris farinosa (True Unicorn Root)
• Areca catechu (Betel Nut)
• Asparagus officinalis (Asparagus)
• Balanites aegyptiaca (Desert Date)
• Daucus carota (Wild Carrot)
• Dioscorea bulbifera (Potato Yam)
• Dioscorea villosa (Mexican Wild Yam)
• Jateorhiza palmata (Calumba Root)
• Momordica charantia (Bitter Melon)
• Smilax spp. (Sarasaparilla)
• Solanum dulcamara (Bittersweet)
• Solanum nigrum (Black Nightshade)
• Tribulus terrestris (Puncture-vine)
• Trigonella foenum-graecum (Fenugreek)
* toxic or restricted plants.

Please read the disclaimer concerning the intent and limitations of the information provided here.
Do not rely solely on the information in this article.

References

Brinker F. A Review of Eclectic female Regulators.Brit. J. Phytotherapy 1997;4,3:123-145.

Brinker F. Herb Contraindications and Drug Interactions. Second edition. Sandy, OR: Eclectic Institute Inc, 1998.

Chen S, et al. Binding characteristics of aromatase inhibitors and phytoestrogens to human aromatase. J Steroid Biochem Mol Biol 1997;61,3-6:107-115.
Abstract: We have evaluated the binding characteristics of three steroidal inhibitors [4-hydroxyandrostenedione (4-OHA), 7alpha-(4'- amino)phenylthio-1,4-androstadiene-3,17-dione (7alpha-APTADD), and bridge (2,19-methyleneoxy) androstene-3,17-dione (MDL 101,003)], four nonsteroidal inhibitors [aminoglutethimide (AG), CGS 20267, ICI D1033, and vorozole (R83842)], and two flavone phytoestrogens (chrysin, and 7,8-dihydroxyflavone) to aromatase through a combination of computer modeling and inhibitory profile studies on the wild-type and six aromatase mutants (I133Y, P308F, D309A, T310S, I395F, and I474Y). We have generated two aromatase models based on the x-ray structures of cytochrome P450-cam and cytochrome P450bm3, respectively. A major difference between the cytochrome P450cam-based and cytochrome P450bm3- based models is in the predicted lengths of helices F and G. In the cytochrome P450cam-based model, helices F and G lie antiparallel and extend across the active-site face of the molecule from one edge to the center, so that the carboxyl-terminal residues of helix F and the N- terminal residues of helix G make a major contribution to the structure of the active site. In the cytochrome P450bm3-based model, both helices are longer and so extend almost all the way across the active-site face of the molecule. Considering the size of the androgen substrate, we evaluated our results mainly based on the cytochrome P450cam model. The mutations involved in this study are thought to be at or near the proposed active site pocket. The inhibitory profile analysis has produced very interesting results and provided a molecular basis as to how seven aromatase inhibitors with different structures bind to the active site of aromatase. Furthermore, the investigation reveals that phytoestrogens bind to the active site of aromatase in a different orientation from that in the estrogen receptor.

Duke JA. Handbook of Phytochemical Constituents of GRAS Herbs and Other Economical Plants . CRC Press, 1994.

Hoffman D. Personal Communication 1999 Phytopharmacology (In Press).

Moore M. Herbal/Medical Contraindications. Albuquerque, NM: Southwest School of Botanical Medicine, 1995.

McQuade-Crawford A. Herbal Remedies for Women Rocklin, CA: Prima Publishing, 1997.

Miksicek R. Commonly occurring plant flavonoids have estrogenic activity. Mol Pharmacol 1993;44(1):37-43.
Abstract: A remarkable diversity of naturally occurring and synthetic compounds have been shown to mimic the biological effects of 17 beta-estradiol by virtue of their ability to bind to and activate the nuclear estrogen receptor. This report extends the family of nonsteroidal estrogens to include several multiply hydroxylated chalcones, flavanones, and flavones. The hormone-like activity of these natural plant products is indicated by their ability to stimulate an estrogen receptor-dependent transcriptional response and to promote growth of estrogen-dependent MCF7 cells in culture. The transcriptional response can be inhibited by the steroidal estrogen antagonist ICI-164,384 and is specific for the estrogen receptor. Evidence is presented to show that selected hydroxylated flavonoids interact directly with the estrogen receptor, based on their ability to compete for the binding of 17 beta- [3H]estradiol to the receptor in cell-free extracts. These compounds are less active, on a molar basis, than 17 beta-estradiol or the synthetic dihydroxystilbene estrogens, but they have potencies comparable to those of other known phytoestrogens. Together, these findings broaden our understanding of the structure-activity relationships for nonsteroidal estrogens and present a series of new chemical prototypes for the future development of potentially useful agonists and antagonists for this nuclear receptor. The wide distribution of weakly estrogenic flavonoid pigments in food crops and medicinal plants raises additional questions about the possible health risks and benefits of these compounds, meriting closer examination of their presence in the human diet.

Takeuchi T, et al. Effect of paeoniflorin, glycyrrhizin and glycyrrhetic acid on ovarian androgen production Am J Chin Med 1991;18:73-78.
Abstract: We have shown that traditional herbal medicine, Shakuyaku-Kanzo-To consisted of Shakuyaku and Kanzo decreased serum testosterone levels in woman and rat. Therefore, paeoniflorin and glycyrrhizin, a main component of Shakuyaku and Kanzo, respectively, and glycyrrhetic acid, a metabolite of glycyrrhizin in vivo, were investigated for the steroid production in the rat ovary on the morning of proestrus. The homogenized tissues of one ovary were incubated in the Dulbecco's modified Eagle medium (pH 7.5) with 100 micrograms/ml of paeoniflorin, glycyrrhetic acid and glycyrrhizin and the medium only (the control) at 37 degrees C for 270 min. After the centrifugation, the concentrations of delta 4-androstenedione, testosterone and estradiol in the supernatants were determined by RIA. The production of the hormones expressed by [concentration x supernatant volume/weight of the ovary] was compared to the control. Paeoniflorin, glycyrrhetic acid and glycyrrhizin decreased significantly the testosterone production but did not change that of delta 4-androstenedione and estradiol. Testosterone/delta 4-androstenedione production ratio was lowered significantly by paeoniflorin, glycyrrhetic acid and glycyrrhizin. Estradiol/testosterone production ratio was increased significantly by glycyrrhetic acid and not changed by paeoniflorin and glycyrrhizin. These results suggest that paeoniflorin, glycyrrhetic acid and glycyrrhizin affect the conversion between delta 4-androstenedione and testosterone to inhibit testosterone synthesis and stimulate the aromatase activity to promote estradiol synthesis by the direct action on the rat proestrous ovary.

Trickey R. Women, Hormones and the Menstrual Cycle. Sydney, Australia: Allen and Unwin, 1998.

Wilbur P. The phytoestrogen debate: Part One. Eur J Herb Med. 1996;2.2:20-26.

Wilbur P. The phytoestrogen debate: Part Two. Eur J Herb Med. 1996 ;2.3:19-26.