Herbal medicine and menopause: an historical perspective.
Abstract: Scientific and consumer interest is growing in the role of phytotherapy in the treatment of menopause related complaints. To date much of the scientific research in this context has focused on the phytoestrogen containing plants, with other herbs traditionally used for menopausal symptoms receiving relatively little attention. Current phytotherapeutic practice thus largely derives its evidence from traditional use. The current paper explores the origins of the recognition of menopause as a syndrome, historical perspectives on menopause with associated treatment aims and treatments, including hormone therapy and plant derived therapies, from the time of Aristotle to the present day.
Article Type: Clinical report
Subject: Menopause (Care and treatment)
Medicine, Botanic (Patient outcomes)
Medicine, Herbal (Patient outcomes)
Women (Health aspects)
Women (Research)
Author: van Die, M. Diana
Pub Date: 12/22/2010
Publication: Name: Australian Journal of Medical Herbalism Publisher: National Herbalists Association of Australia Audience: Academic Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2010 National Herbalists Association of Australia ISSN: 1033-8330
Issue: Date: Winter, 2010 Source Volume: 22 Source Issue: 4
Topic: Event Code: 310 Science & research
Geographic: Geographic Scope: Australia Geographic Code: 8AUST Australia
Accession Number: 254971791
Full Text: Introduction

Herbal medicine use by midlife and menopausal women is widespread in Australia, as is use of other complementary and alternative medicine (CAM) modalities (Gollschewski 2004, van der Sluijs 2007). In 2004 the prevalence of CAM use during menopausal years was found to be 82.5% in South East Queensland (Gollschewski 2004) and a 2003-2004 Sydney based study reported 53.8% of 45-65 year old women to have visited a CAM practitioner and/or used a CAM product during the previous year for the alleviation of menopausal symptoms (van der Sluijs 2007).

In terms of phytotherapy, although there is a growing body of scientific research on remedies used in the Anglo-American tradition* for the alleviation of menopause related symptoms, this has largely focused on the phytoestrogen containing plants, while other herbs traditionally used in this context have received relatively little attention (Nedrow 2006). Thus evidence for current clinical administration of many herbs continues to be derived from traditional practice. When investigating the source of traditional applications, it soon becomes apparent that specific references to treatments for 'menopause' do not appear in the published literature until as recently as the nineteenth century.

This paper examines the historical treatment of menopause related symptoms in the contexts of the recognition of menopause as a syndrome and the origins of current practice of phytotherapy in the Anglo-American tradition.

A modern presentation?

Menopause, the cessation of menstruation, marks the end of the reproductive phase of a woman's life. Although a natural event, the transition from regular cycling to the final menstrual period (FMP) and beyond into postmenopause is commonly accompanied by physiological and/or psychological symptoms. In addition the incidence of certain disorders such as breast cancer, noted by Burns in 1814, has long been observed to increase in postmenopausal women (Utian 1999).

While not a condition of the modern age, the climacteric or menopause transition had received relatively little attention in the published literature before the 1890s. Factors contributing to this include the shorter life expectancy in earlier times, which meant that many women did not reach menopause. At the beginning of the nineteenth century average life expectancy was 36.5 years for a female (Goldzieher 2000) increasing to 49 for an American female by the early 1900s (Speroff 1999). Other reasons for menopausal women presenting less frequently to medical practitioners may well have included the cost of healthcare and social taboos regarding discussing such an intimate topic with male doctors.

Early references to menopause

References to menopause or the climacteric appeared in the literature as far back as Aristotle's times (384-322 BC) when menstruation was observed to cease at the age of 40.5 years (Utian 1997). In the sixth century Aetios of Amida wrote that 'menstruation does not cease before the thirty fifth year, nor does it (usually) continue after the fiftieth year. Meanwhile menstruation may in the rarest cases last as late as the sixtieth year. Fat women lose their periods very early' (Amida 1950).

References to associated symptoms

It was not until 1816, with the coining of the term la menespausie by the French physician CPL De Garndanne, that climacteric complaints were recognised as a syndrome with a common cause (van Keep 1990). However the association of the cessation of menstruation with other organic and emotional problems had been made in 1777 by Leake in the chapter Cessation of the periodical discharge in the decline of life and the disorders arising from that critical change of constitution. He observed that some women at this critical time of life (one meaning of the term 'climacteric') were 'subject to pain and giddiness of the head, hysteric disorders, colic pains and female weakness .. the rheumatism, pains in the limbs and eruptions on the skin at this time frequently appear and also cancerous tumors of the breast or womb. Women are likewise sometimes affected by low spirits and melancholy'. A reference to flushings and night sweats is also made in this chapter 'where the patient is delicate and subject to female weakness, night sweats or habitual looseness, with flushings in the face and hectic fever' (Leake 1777).

Flushes and perspiration appear in the 1857 writings of Edward Tilt (1857), the British physician who wrote one of the first full length books on the 'change of life' in which he lists a wide range of 'morbid liabilities at the change of life' as well as their treatments. He describes the disorders most likely to be experienced by the different temperaments, with 'women of nervous temperament suffering more than all, particularly during the dodging time' (perimenopause) whereas 'women with a marked biliary temperament are likely to suffer much from the various forms of insanity, if the nervous be associated with the bilious temperament'. Tilt's recommended treatment for reducing sweating was to 'diminish the mass of blood by taking 2 or 3 ounces from the arm at successive months' since 'the relative superabundance of blood is often the cause of the superabundant heat, and therefore of the perspirations' (Tilt 1857). To relieve the irritability of the nervous system, sedative preparations were recommended (Tilt 1857).

Historical treatments

Menstruation was seen as a form of detoxification of poisons from the woman's blood (Madvai 1993) and the menopause as an accumulation of unexpelled toxins that could lead to the development of diseases such as cancer, gout and rheumatism and other mental and physiological symptoms. Treatment was aimed at either encouraging menstruation by the use of herbal emmenagogues, or removing these unexpelled toxins by other purification methods such as blood letting, purging, applying leeches to the genitalia or cervix, setons (threads of horsehair or strips of linen inserted beneath the skin to provide drainage) or induction of sweating (Wilbush 1988).

Treatments recommended by Leake in 1777 for curing specific diseases or alleviating psychological symptoms that were associated with the menopause likewise included blood letting and purgatives, also reduced intake of animal food, 'a spare and simple diet consisting chiefly of vegetables, fish and spoon meats, and increased exercise'. For the delicate patient with flushings and night sweats, ass's milk, jellies, raw eggs and cooling fruits were recommended with 'at meals half a pint of old clear London Porter or a glass of rhenish wine' (Leake 1777).

The dawn of hormone replacement therapy (now hormone therapy)

The ancient form of organotherapy, or glandular therapy, became popularised in the late 19th century with injections of 'testicular juice' being used for rejuvenation of men and to combat feminine debility. Ovarian therapy, the administration of crude ovaries, powdered ovaries and powdered ovarian tablets, was used for physiological and surgical menopause and in 1896 clinical trials conducted in Germany recommended substitution with ovarian therapy as a means of alleviating menopausal symptoms (Kopera 1991).

The first scientific evidence of the existence of hormones was provided in 1902, and the term 'hormone' adopted in 1905 (Kerr 1954). This replaced the earlier term 'internal secretion' coined by the French professor, Claude Bernard, although the notion of internal secretions by cells dates back to 1775 with the French physician De Bordeau (Kerr 1954). It was not until 1926 that estrogenic hormones were detected by the chemists Loewe and Lange in human urine and the name 'estrin' was given by Parkes and Bellerby to the hormone extracted from the ovary (Davis 2005). Estrone was isolated from the urine of pregnant women in 1929 by Butenandt and estriol discovered in human pregnancy urine in 1930 (Utian 1999). The most potent form of estrogen in the female body, estradiol, was isolated from sow's ovaries in 1930 by Marrian, although it was not until 1940 that [beta]-estradiol was demonstrated in human pregnancy urine and the placenta (Davis 2005). In a comprehensive article on the history of HRT, Davis (2005) outlines the development, promotion and challenges of hormone therapy.

Progesterone was first isolated in 1934 from corpus luteum extracts injected into rabbits. This corpus luteum hormone was called progesterone because it maintained gestation. In 1943 it was synthesised by Marker and colleagues from the precursor saponin, diosgenin, from Mexican wild yams (Dioscorea composita), that could be converted into synthetic progestin quite easily with a few chemical steps (Bruneton 1995). Diosgenin had previously been isolated from the rhizomes of D. villosa (wild yam) in 1940 (Marker 1940), but because of the relatively low yield from this species, the richer sources, tubers of D. composita and D. floribunda from Mexico and Central America came to be used by the pharmaceutical industry (Bradley 1990).

The first commercially available estrogen, Progynon[R] was developed in 1928 from animal placentas and subsequently from the urine of pregnant women (Schmidt-Gollwitzer 2001). A substance resembling estrin was manufactured from the urine of pregnant women and launched in the US in 1933 but faced the problem that limited raw material for production could not meet market demand (Davis 2005). The discovery of estrogens in pregnant mare's urine in the 1930s led to the creation of Premarin[R] (conjugated estrogens from pregnant mare's urine) and it was launched onto the market in North America in 1941-2 as the first orally active estrogen (Speroff 1999). By 1975 it had become the most dispensed drug in the United States, reportedly taken by 6 million women (Davis 2005). The preference for the combination of estrogen with cyclic progestin therapy arose from the discovery in the 1970s of the link between unopposed estrogen and endometrial cancers (Goldzieher 2000). Progestins had been reported to protect against this adverse effect by counteracting the proliferative effects of estrogens (Whitehead 1981).

By the 1960s menopause had come to be viewed as a deficiency disease, a term used by the New York gynacologist, Wilson, in his book Feminine Forever (Wilson 1966) (financed by Ayerst Laboratories). This, according to Davis and colleagues, further contributed to the success of hormone replacement by promoting its virtues in alleviating the symptoms of menopause as well as helping to maintain youth and sexuality (Davis 2005).

Plant therapies for menopausal symptoms

Specific references to the climacteric period do not appear in herbal texts until the mid 1800s. However, as mentioned above, treatments were historically aimed at reinstating menstruation using, among other means, herbal emmenagogues. It seems likely therefore that treatment of menopausal symptoms employed herbs indicated for amenorrhoea, or whose virtues included 'provoking women's courses', such as Leonurus cardiaca (motherwort) listed in the 17th century Culpeper's Complete Herbal (Culpeper 1653). Its other virtues included treatment of 'trembling of the heart, fainting and swooning', a possible reference to the symptoms of dizziness, heart palpitations and feeling faint that are currently associated with menopause, and 'making mothers joyful' (Culpeper 1653). Motherwort remains listed in the British Herbal Pharmacopoeia (BHP) of 1983 as indicated for amenorrhoea (BHMA 1983).

In 1853 Pereira refers to herbal treatment of symptoms associated with the climacteric period with Lolium temulentum (bearded darnell) which had been successfully used by Fantoni 'in the case of a widow who, at the climacteric period, was affected with giddiness, headache and epistaxis which had resisted various other remedies' (Pereira 1853).

Senecio aureus (life root) is a herb for amenorrhea and menorrhagia referred to in a 19th century text that retains an indication for menopause related symptoms in the current BHP (BHMA 1983). In 1870 Scudder's Specific Medication and Specific Medicines lists it as a uterine tonic for amenorrhea, dysmenorrhea and menorrhagia. In 1931 Mrs Grieve refers to its emmenagogue action and the 1983 BHP includes 'menopausal neurosis' as one of its indications, and specific indications as 'emotional and vascular instability, including the hot flush, associated with the menopause'. It 'may be used with Hypericum perforatum (also indicated for menopausal neurosis), Avena sativa (for menopausal neurasthenia), Viburnum prunifolium and Anemone pulsatilla in menopausal disturbances'.

Cimicifuga racemosa, synonymous with Actaea racemosa (black cohosh), now widely employed for the treatment of hot flushes, made its way into the Eclectic Dispensary in 1852 as a highly regarded treatment for amenorrhoea (Duke 1985), having been adopted by the European colonists from the native Americans; the Cherokee and Iroquois people for 'gynecopathy (diseases peculiar to women) and rheumatism' (McKenna 2001).

Other 19th century references to the climacteric include herbs for uterine hemorrhage attending the menopause such as Viburnum prunifolium (black haw) and Hydrastis canadensis (golden seal) 'climacteric haemorrhage' in the 1898 King's American Dispensatory (Felter 1983, Lloyd 1887). Herbs in the same work that were recommended for other physiological and emotional symptoms attending the climacteric/menopause include:

* Cypripedium pubescens (lady's slipper) whose specific indications include insomnia, nervous irritiability, menstrual irregularities, with despondency; tendency to dementia at climacteric.

* Viburnum prunifolium (black haw) recommended by Prof Howe for the debility of the second climacteric.

* Passiflora incarnata (passion flower) for various forms of neuralgia, many reflex painful conditions incident to the menopause.

* Ignatia amara (ignatia) for nervous atony, where the patient is cold and especially when coldness of the extremities is a distressing feature of the menopause.

* Cannabis indica (Indian cannabis) for migraine, nervous headache, facial and other neuralgias, attending the menopause, as well as those depending upon fatigue, relieved when nervous depression is the most marked symptom.

Winterburn in 1882-3 listed Sanguinaria canadensis (blood root) for 'congestion to the head and lungs, especially at the climacteric'. In 1902 Potter recommended Valeriana officinalis (valerian) for 'hypochondriasis, especially at the climacteric period'.

Plant remedies specifically for hot flushes

References to plant remedies for hot flushes appear in Kings Dispensatory of 1898: Aconitum napellus (aconite) is recommended for 'disorders of the menopause, with alternate chills and flushes of heat, with rush of blood to the head, cardiac palpitation, dyspnea, gastric fullness, sense of distension in the bladder, with frequent attempts to pass urine (Locke)' (Felter 1983).

References can also be found in early 20th century herbal texts. For example the Lloyd brothers drug pamphlets of 1908 refer to Cactus grandiflorus (Selenicereus grandiflorus) for the flushes as well as emotional conditions: 'Dr Lydia Ross has made extended and satisfactory observations concerning the influence of Cactus in the disorders of women. She especially advises it where there are 'hot flashes during the climacteric', sometimes given in conjunction or alternation with Helleborus niger (black hellebore). 'The melancholia, irritability of temper, nervousness, neuralgia, hypersensitiveness, vague fears and fantasies present during the menopause are influenced by Cactus and pulsatilla alone or in conjunction or in alternation'. This indication is echoed in 1919 by Ellingwood, who lists Cactus for 'the hot flashes which are so disagreeable during the climacteric. The dose of specific cactus varies from a half minim to two or three minims' [1 mL = 15 minims (BHP); 1 minim = 1 drop (German Commission E)].

In Ellingwood's Therapeutist of 1908, it is reported that gelsiminine from Gelsemium sempervirens (yellow jasmine) 'will check the hot flashes that occur during or after the menopause in nervous, plethoric or relaxed women at a dose of 1/250 grain' (Dougherty-Trexler 1908) and elsewhere a single dose of 'ten drops of specific gelsemium, if necessary followed up by 3 drop doses every hour is excellent for the hot flashes that are apt to occur during the menopause' (Henschen 1908).

Many of the above mentioned remedies are no longer commonly used in phytotherapeutic practice that follows the Anglo American tradition. Some have simply fallen out of popularity in favour of different herbs based on greater physiological understanding, while others such as Ignatia, Gelsemium, Aconitum, Cactus and Sanguinaria are now used preferentially in homeopathic potencies, in some cases their use in material doses having been scheduled. Current phytotherapeutic treatment of menopausal symptoms involves herbs with a tradition of less than three generations of use, (100 years of use is the minimum requirement for the label 'traditional use' according to the Therapeutic Goods Administration in Australia) such as Dioscorea villosa (wild yam), Cimicifuga racemosa (black cohosh), Helonias dioica/ Chamaelirium luteum (false unicorn root) and Vitex agnus-castus (chaste tree/berry).

More recent introductions

The earliest references to the treatment of menopausal complaints with Dioscorea villosa appear after the discovery of yams as a prized source of the precursor saponin diosgenin for the synthesis of progestins (Marker 1947) and other sex hormones (Bohonos 1966). The results of rodent studies published in 1992 by Aradhana and colleagues supported diosgenin's estrogenic activity and augmentation of estrogenic acitivity.

Chamaelirium luteum (also known as Helonias dioica, Helonias lutea, Veratrum luteum, false unicorn root) is referred to by Cook in his 1869 The Physiomedical Dispensatory, for menorrhagia with laxity and depression, as well as restoring the menstrual flow, possible allusions to menopausal symptoms. 'But its most prominent and valuable action is upon the uterine organs where it scarcely has an equal in menorrhagia, and similar enfeebled conditions. Its tonic influence is peculiarly efficacious in arresting too excessive menstruation and lochia, when associated with laxity and depression. That these influences over the uterine function are due to the pure tonic action of the agent, is at once seen in the fact that it is a valuable article to restore the menstrual flow when this is absent from sheer inability of the generative organs. It is a valuable ingredient in the compounds called 'Woman's Friend and Female Restorative'. However its role in the treatment of menopausal symptoms does not appear until the twentieth century. In 1950 Costello and Lynn reported that estrogenic effects of Helonias dioica were found in animal studies.

References to the use of Vitex agnus-castus as a sitz bath for 'diseases of the uterus' can be found as far back as Hippocrates in 4th century BC and Dioscorides in AD77 (Hawley 1995). One of the great Renaissance herbalists, Gerard, recommended it for inflammation of the uterus and as an emmenagogue (Hobbs 1990). Modern interest in Vitex has been attributed to the scientific research on its effects on the female reproductive system conducted by Dr Gerhard Madaus in Germany in 1930. The benefits of Vitex for menopausal complaints were reported in 1972 in a collective report on the clinical experience of five practitioners with Agnolyt[R] (a patent medicine extracted from dried Vitex berries) by Attelmann and colleagues in Germany. A review of the evidence for Vitex in this context has been published elsewhere (Van Die 2009).

Madaus in 1938 wrote that Cimicifuga/Actaea racemosa (black cohosh) was recommended for climacteric symptoms, at a higher dose for somatic symptoms and a lower dose for the neurological symptoms. Remifemin[R], an extract of Cimicifuga racemosa has been used in Germany for the relief of menopausal symptoms since the mid 1950s (Jellin 1999). Positive results of uncontrolled studies with Remifemin[R] in menopausal women were first published in the German literature in 1957 (Kesselkaul) and 1958 (Kramer). Reports from clinical trials of its effectiveness in specifically relieving hot flushes are found from 1982 onwards (ESCOP 2003).

Hypericum perforatum (St John's wort) is recommended for 'menorrhagia, hysteria, nervous affections with depression' in Kings Dispensatory of 1898 and subsequently in the 1918 Dispensatory of the United States of America for hysteria, mania and .. hemorrhages. It formerly enjoyed a great reputation for the cure of demoniacs' (Remington 1918). In 1938 Dr Gerhard Madaus states that 'in the area of the gynecology Hypericum makes a substantial contribution, for menopausal bleeding it is indicated with Viscum album' (mistletoe). The 1983 British Herbal Pharmacopoeia lists Hypericum as specific for 'menopausal neurosis', and a study published in 1986 (Warnecke) reported it to be of comparable efficacy to diazepam for climacteric depression. Reference to its potential benefit in hot flushes appears in the published research literature in the 1990s (Grube 1999). Recent randomised controlled trials provide some support for its use in hot flushes (Abdali 2010), quality of life (Al-Akoum 2009) and premenstrual like symptoms during the menopause transition (Van Die 2009).

Summary

While references to menopause, its associated symptoms and treatments have appeared throughout history, it was only recognised as a syndrome with a common cause in 1816 when the term 'la menespausie' was first coined. It was not until the 1890s that it began to receive more attention in the published literature, possibly due to the increasing life expectancy which meant that more women reached menopausal age. Herbal remedies specifically for hot flushes also began to appear in late nineteenth century texts. However it is possible that prior to this time menopause related symptoms were not recognised as such, and therefore not differentiated from the same symptoms occurring at other stages of reproductive life. Hence they may have been treated accordingly with herbal emmenagogues for amenorrhea, or remedies for menorrhagia, depression and hysteria that are listed in earlier works.

Acknowledgements

Professors Helena Teede, Henry Burger and Ken Greenwood, PhD supervisors, and Associate Professor Kerry Bone, PhD consultant, for their critical review. The material in this article is derived from the author's thesis accepted by RMIT University in 2009 for her PhD.

References

Abdali K, Khajehei M, Tabatabaee HR. 2010. Effect of St John's wort on severity, frequency, and duration of hot flashes in premenopausal, perimenopausal and postmenopausal women: a randomized, double-blind, placebo-controlled study. Menopause 17:2;326-31.

Al-Akoum M, Maunsell E, Verreault R, Provencher L, Otis H, Dodin S. 2009. Effects of Hypericum perforatum (St John's wort) on hot flashes and quality of life in perimenopausal women: a randomized pilot trial. Menopause 16:2;307-14.

Amida Ao. 1950. Aetios of Amida: The Gynaecology and Obstetrics of the Vlth Century, A.D. translated from the Latin Edition of Cornarius. 1542. Fully annotated by James V. Ricci. Philedelphia: Blakiston.

Aradhana Rao AR, Kale RK. 1992. Diosgenin: a growth stimulator of mammary gland of ovariectomized mouse. Indian J Exp Biol 30:5;367-70.

Attelmann H, Bends K, Hellenkemper H, Warkalla H. 1972. Agnolyt[R] in the treatment of gynecological complaints (In German). Z Praklin Geriatr 2;239-43.

BHMA. 1983. British Herbal Pharmacopoeia. Bournemouth: The British Herbal Medicine Association.

Bohonos N, Piersma H. 1966. Natural Products in the Pharmaceutical Industry: The Biologist in the Pharmaceutical Industry. Bio Sci 16:10;706-14, 29.

Bradley PR. 1990. British Herbal Pharmacopoeia. British herbal compendium : a handbook of scientific information on widely used plant drugs. Bournemouth: British Herbal Medicine Association.

Bruneton J. 1995. Pharmacognosy, Phytochemistry, Medicinal Plants. Paris: Lavoisier Pub.

Cook W. 1869. The Physiomedical Dispensatory.

Costello CH, Lynn EV. 1950. Estrogenic substances from plants; glycyrrhiza. J AmPharm Assoc 39:3;177-80.

Culpeper N. 1653. Culpeper's complete Herbal: consisting of a comprehensive description of nearly all herbs with their medicinal properties and directions for compounding the medicines extracted from them. Slough England: W Foulsham & Co.

Davis SR, Dinatale I, Rivera-Woll L, Davison S. 2005. Postmenopausal hormone therapy: from monkey glands to transdermal patches. J Endocrinol 185:2;207-22.

Dougherty-Trexler D. 1908. Specific Sedatives. Ellingwood s Therapeutist 2:4;24.

Duke JA. 1985. CRC handbook of medicinal herbs. Boca Raton: CRC Press.

Ellingwood F. 1983. The American Materia Medica, Therapeutics and Pharmacognosy 1919. 11th edn. Portland: Eclectic Medical Pubs.

ESCOP. European Scientific Cooperative on Phytotherapy. 2003. ESCOP Monographs: the scientific foundation for herbal medicinal products. Exeter: ESCOP in collaboration with Thieme.

Felter H, Lloyd J. 1983. Kings American Dispensatory 1898. 18th ed. Portland: Eclectic Medical Pubs.

Goldzieher W. 2000. Historical Perspectives. In: Lobo R, Kesley J, Marcus R, eds. Menopause: Biology and Pathophysiology. San Diego: Academic Press.

Gollschewski S, Anderson D, Skerman H, Lyons-Wall P. 2004. The use of complementary and alternative medications by menopausal women in South East Queensland. Womens Health Issues 14:5;165-71.

Grieve M. 1988. A Modern Herbal. London: Penguin.

Grube B, Walper A, Wheatley MD. 1999. St. John's Wort Extract: Efficacy for Menopausal Symptoms of Psychological Origin. Advances Ther 16:4;177-86.

Hawley R, Levick B, eds. 1995. Women in antiquity : new assessments. London: Routledge.

Henschen GE. 1908. Trifacial Neuralgia-Hot Flashes. Ellingwood's Therapeutist 2:12;36.

Hobbs C. Vitex: The Women's Herb. 2nd edn. Santa Cruz: Botanica Press.

Jellin JM, Batz F, Hitchens K. 1999. Natural medicines comprehensive database. Stockton CA: Therapeutic Research Faculty.

Kerr J, Johnstone R, Phillips M. 1954. Historical review of British obstetrics an gynaecology 1800-1950. London: Livingstone.

Kesselkaul O. 1957. Treatment of climacteric disorders with remifemin. Med Monatsschr 11:2;87-8.

Kopera H. 1991. The dawn of hormone replacement therapy. Maturitas 13:3;187-8.

Kramer H, Geisenhofer H. 1958. Experiences with the Cimicifuga preparation remifemin. Ther Ggw 97:6;238.

Leake J. 1777. Chronic or Slow Diseases peculiar to women. London: Baldwin.

Lloyd J, Lloyd C. 1887. Drugs and Medicines of North America. 18th edn. Cincinatti: Ohio Valley Co.

Lloyd J. 1908. Lloyd Brothers plant drug pamphlets 1897-1915.

Madaus G. 2938. Lehrbuch der Biologischen Heilmittel. Leipzig: Georg Thieme/Verlag.

Marker RE, Turner D, Ulshafer PR. 1940. Sterols. CIV. Diosgenin from Certain American Plants. J Am Chem Soc 62:9;2542-43.

Marker RE, Wagner R, Ulshafer PR, Wittbecker EL, Goldsmith DP. 1947. Steroidal Sapogenins. J Am Chem Soc 69;2167-230.

McKenna DJ, Jones K, Humphrey S, Hughes K. 2001. Black cohosh: efficacy, safety, and use in clinical and preclinical applications. Alt Ther Health Med 7:3;93-100.

Medvai V. 1993. The History of Clinical Endocrinology: a Comprehensive Account of Endocrinology from Earliest Times to Present day. New York: Parthenon Publishing.

Nedrow A, Miller J, Walker M, Nygren P, Huffman LH, Nelson HD. 2006. Complementary and alternative therapies for the management of menopause-related symptoms: a systematic evidence review. Arch Intern Med 166:14;1453-65.

Pereira J. 1853. The Elements of Materia Medica and Therapeutics. Vol II (Part 1). Philadelphia: Blanchard & Lea.

Remington JP, Wood HC. 1918. The Dispensatory of the United States of America. Philadelphia: Grigg & Elliot.

Schmidt-Gollwitzer K. 2001. Estrogen/hormone replacement theerapy present and past. Gynaecol Endocrinol 11-16.

Scudder JM. 1870. Specific medication and Specific medicines. Cincinnati: Wilstach, Baldwin & Co.

Speroff L, Glass R, Kase N. 1999. Clinical Gynaecological Endocrinology and Infertility. Baltimore: Lippincott, Williams & Wilkins.

Tilt E. 1857. Change oflife in health and disease. London: Churchill.

Utian WH. 1997. Pieter van Keep Memorial Lecture. Menopause: a modern perspective from a controversial history. Maturitas 26:2;73-82.

Utian WH. 1999. An historical perspective of natural and surgical menopause. Menopause 6:2;83-6.

Van der Sluijs CP, Bensoussan A, Liyanage L, Shah S. 2007. Women's health during mid-life survey: use of CAM by symptomatic women transitioning through menopause in Sydney. Menopause 14:3;397-403.

Van Die M, Burger H, Teede H, Bone K. 2009. Vitex agnuscastus (Chaste-tree/berry) in the Treatment of Menopauserelated Complaints. JACM 15:8;853-62.

Van Die MD, Bone KM, Burger HG, Reece JE, Teede HJ. 2009. Effects of a combination of Hypericum perforatum and Vitex agnus-castus on PMS-like symptoms in late-perimenopausal women: findings from a subpopulation analysis. JACM 15:9;1045-8.

Van Keep PA. 1990. The history and rationale of hormone replacement therapy. Maturitas 12:3;163-70.

Warnecke G. 1986. Beeinflussung klimakterischer Depressionen. Therapieergebnisse mit Hypericin (Johanniskraut-Extract). Z Allg Med 62:1111-13.

Whitehead MI, Townsend PT, Pryse-Davies J, Ryder TA, King RJ. 1981. Effects of estrogens and progestins on the biochemistry and morphology of the postmenopausal endometrium. N Engl J Med 305:27;1599-605.

Wilbush J. 1988. Climacteric disorders--a historical perspective. In: Studd J, Whitehead M, eds. The Menopause. Oxford: Blackwell Scientific Pubs.

Wilson RA. 1966. Feminine Forever. NY: M Evans and Co.

Winterburn GW. 1882-3. In: Wilder A, ed. Transactions of the National Eclectic Medical Association 1882-3.

Dr Diana van Die is a Melbourne based medical herbalist, lecturer and researcher, who completed her PhD on menopausal symptoms in 2008 at RMIT Melbourne Australia. Her scientific publications relate to menopausal symptoms, PMS like symptoms, Vitex agnus-castus and issues surrounding the placebo response. She has presented at international conferences and received the Australasian Menopause Society Scientific Award 2009 for the most meritorious contribution to the field of menopause by an Australian or New Zealand investigator.

M Diana van Die, PhD (1)

School of Health Sciences (Comp Med), RMIT University, PO Box 71, Bundoora, Victoria Australia 3083 email: diana.vandie@rmit.edu.au, phone 0403 011 151, fax 03 9925 6539

(1) Royal Melbourne Institute of Technology-University, Bundoora Victoria Australia; University of Melbourne, Department of general Practice, Carlton Victoria Australia
Gale Copyright: Copyright 2010 Gale, Cengage Learning. All rights reserved.