Course: Master of Health Science (Herbal Medicine) University: University of New England Unit: Herbal Therapeutics III Lecturer: Associate Professor Kerry Bone Student Name: Kamma Chapman A) Patient 1 • 42 year old woman. • 1 child born, difficulty conceiving since. • History of miscarriages; lost triplets at 14 weeks 4 years prior to seeking herbal treatment, lost a single pregnancy at 14 weeks 4 years later. • Treated with Clomid, which caused her to develop ovarian cysts and amenorrhoea. • 38 day cycle, suffers PMS, bloating, bursts of anger. • Suffers headaches due to poor sleep, lies awake worrying • Takes paracetamol for headaches • She is depressed due to her inability to conceive, very stressed, not coping well with daily life. • Blood tests conducted a year ago show elevated prolactin level, all other hormones are at normal levels Introduction: Difficulty with conception, often termed infertility, becomes increasingly common in women over the age of 35 years (Brzakowski 2009:F3-7). According to the American Society for Reproductive Medicine three out of four people overestimate by five years the rapid decline in female fecundity, with prime childbearing age occurring up to the age of 32 years for females and a rapid decline at 35, instead of 40 as is commonly believed. By the mid thirties almost 25% of women are infertile and by age 43 it is unusual to still be fertile (Brzakowski 2009:F3-7). It is, however wise to ensure that both the man and woman trying to conceive have been examined and medically tested (by a specialist gynaecologist) to ensure therapeutic focus on the correct patient (Brzakowski 2009:F3-7). If this is not determinable, therapy would be most effectively directed at both the man and the woman (Brzakowski 2009:F3-7). In the case of the patient detailed above the reality of age must be considered. At 42 years of age conception occurs at a significantly lower rate (Brzakowski 2009:F3-7). Phytotherapy, however, should be considered along with lifestyle and dietary factors for patients experiencing difficulty with conception related to anovulatory cycles, defective luteal function, viscous cervical mucous and immunological rejection of sperm (Mills and Bone 2000:238-246). Still yet 20-30% of patients suffer idiopathic infertility of no known cause (Brzakowski 2009:F3-7). Although the patient has been treated previously with clomiphene (Clomid), a selective oestrogen receptor modulator (SERM) used mainly in female infertility due to anovulation, she evidently experienced a common adverse effect of this drug in the form of ovarian cysts (Bates 2009: 586-7). Most ovarian cysts are functional in nature and benign (Brisholt 2009:165-69). There are three types; Graafian, Luteal and Haemorrhagic, the second type being the most likely in this patient (Brisholt 2009 :165- 69). They are frequently found in women of childbearing age and up to 14.8% of postmenopausal women (Brisholt 2009:165-69). It is not clear as to whether the ovarian cysts still persist in the patient as they usually resolve after 2-3 menstrual cycles (Brisholt 2009:165-69). Hyperprolactinaemia is the presence of higher than normal prolactin levels in the blood. Normal levels are less than 580 mIU/L for women and less than 450 mIU/L for men (Patel 2007:455-9). Prolactin is a peptide hormone produced by the anterior pituitary gland, which is normally associated with lactation and breast development during pregnancy (Warrell 2003:550-555). Higher than normal levels of prolactin can cause disruptions in the normal menstrual period and infertility (Patel 2007:455-9). Hyperprolactinaemia can occur as a normal body change during pregnancy and lactation (Warrell 2003:550- 555). Abnormal function or stimulation of the prolactin-secreting cells in the pituitary gland can cause prolactin levels to rise (Mancini 2008: 67-99). Pituitary tumours are the most common cause of this (Mancini 2008: 67-99), often treated in conventional medicine with Cabergoline and Bromocriptine (Coleo 2006:200-10). Hyperprolactinamia can also be caused by prescription drugs and less commonly heavy metals. The hyperprolactinaemia from which the patient is suffering may be due to the emotional stress she is experiencing (Warrell 2003:550- 555), in direct relationship to her difficulty conceiving. The hyperprolactinaemia could also be the source of the patient’s difficulty to conceive (Warrell 2003:550-555) and contributing to the premenstrual syndrome (Warrell 2003:550-555). Although a common condition; up to 1.5 million women in the United Kingdom experience significant, disruptive symptoms (Wyatt 2001), the cause of PMS is not fully understood. PMS is defined as physical, behavioural or psychological symptoms that recur on a cyclical basis during the luteal phase of the menstrual cycle. The symptoms should resolve completely by the end of menstruation and women should be free of symptoms for at least one week between menstruation and ovulation (O’Brien 1997). Over 150 symptoms have been attributed to PMS, however, the most common are; headache, tension, anxiety, irritability, depression and bloating, among others (O’Brien 1997). An abnormality of the hypothalamic-pituitary axis has been proposed as women suffering from PMS have significantly higher levels of prolactin, especially in the second and third week of their cycles (Tesch 2003:1-3) (Sugino 2006:440-6). Abrahams (1983:446-464) suggests five distinct subgroups of PMS. The patient in this case displays symptoms corresponding with types A, C and D, as well as the bloating listed in PMS type H (Abrahams 1983:446-464). The herb Vitex agnus castus showed good results in a clinical trial for PMS types A, D and H, (Shaw 2009) detailed further in the rationale below. Treatment options are varied and include surgery, antidepressants, non-steroidal anti-inflammatory drugs (NSAID’s), hormone preparations, dietary supplements, cognitive therapy and exercise. Surveys show that women are increasingly finding phytotherapy more helpful than conventional medicine in the case of PMS (Corney 1991). The modern phytotherapeutic approach to treatment of endocrine disorders, with reference to this case aims to: for PMS; to correct any hormonal imbalance, specifically normalise prolactin levels using Vitex (White Peony and Licorice were also considered, but decided against, in this case, to avoid over-prescribing and assist compliance) (Mills 2000: 240-2246). The normalization of prolactin levels in itself may be the key with this patient as the inability to conceive may be caused by the hyperprolactinaemia and leading to her subsequent stress and depression, which can in turn aggravate PMS (Tesch 2003:1- 3) (Sugino 2006:440-6). The Vitex will also assist normalisation of her menstrual cycle and establish regular ovulation as the current 38 day cycle is longer than the normal 28 days, suggesting there may be a possible corpus luteum defect, which is again associated with hyperprolactinaemia (Schellenberg’s 2001:134-7). Correct essential fatty acid status with Evening primrose oil, which is especially indicated in prostaglandin deficiency (PMS type C) and connected with the headache symptom (Mills 2000: 240-2246). The EPO will be dispensed at a subsequent visit, if required, to avoid overloading the patient. Treat the main physical symptoms as they occur (Wuttke 2003:348-57). In this case the headaches could also be treated with a herbal analgesic such as Willow bark or Yellow jasmine, in place of the Paracetamol. However, in light of the number of herbs used and keeping in mind patient compliance and practicality, these herbs could be introduced at a later stage if still required. A hepatic tonic, namely Milk thistle is included to aid phase I/II detoxification and subsequently hormone clearance to assist normalisation of prolactin levels. A key component of the phytotherapeutic approach to treatment of PMS is to treat the emotional disturbances (Wuttke 2003:348-57). St John’s Wort is used to treat the depression, Valerian, as a mild sedative to treat the insomnia. The patient is also very stressed, so Tribulus is used as a tonic that will be supportive, but not overly stimulating (Samy 2008: 302-12). The treatment approach is comprehensive in the case of this patient as she is not coping with daily life, suffering insomnia and is very stressed, all whilst trying to conceive at an age where conception will be more of a challenge (Brzakowski 2009:F3-7). Schisandra has been considered in this case, as it would be most appropriate to provide a number of necessary actions as indicated above however, decided against as a precautionary measure, as it is contraindicated in pregnancy (Mills 2000:46). Tribulus is also contraindicated in pregnancy (Mills 2000:46), however has been selected in light of its fertility promoting action and ease of discontinuation upon conception, as it is dispensed as a tablet. It is also recommended that Chaste tree be used cautiously in pregnancy (Schellenberg’s 2001:134-7). That noted, the patient will be advised to monitor her conception status closely as the treatment outlined here is to promote conception, treat PMS and the additional symptoms and will be discontinued once conception occurs. Treatment will be re-evaluated, based upon patient feedback. As the patient is not coping with daily life a follow up appointment is recommended in one week to assess progress with the insomnia and stress. Referral to a counselling psychologist, experienced in fertility counseling to discuss the anger, stress and ‘lying awake at night worrying’ is recommended in conjunction with phytotherapy, along with offering the patient concurrent treatment with a medical fertility specialist (Zarkova 1982: 223-234). Treatment Goals and Herbs Considered Action Herb: Common Name Herb: Botanical Name Prolactin inhibitor Chaste tree Vitex agnus-castus White peony Paeonia lactiflora Licorice Glycyrrhiza glabra Nervine tonic Korean ginseng Panax ginseng St John’s Wort Hypericum perforatum Schisandra Schisandra chinensis Skullcap Scutellaria lateriflora Adaptogen Schisandra Schisandra chinensis Siberian ginseng Eleutherococcus senticosa Withania (Ashwaganda) Withania somnifera Korean ginseng Panax ginseng Tonic (for the general body) Siberian ginseng Eleutherococcus senticosa Withania (Ashwaganda) Withania somnifera Tribulus Tribulus terrestris Hepatic tonic Schisandra Schisandra chinensis Dandelion root Taraxacum officinale Milk Thistle Silybum marianum Ovulation normaliser White peony Paeonia lactiflora Licorice Glycyrrhiza glabra Dong quai Angelica sinesis Oestrogen modulator Tribulus Tribulus terrestris White peony Paeonia lactiflora Licorice Glycyrrhiza glabra Fertility agent Tribulus Tribulus terrestris Action Herb: Common Name Herb: Botanical Name Female tonic Chaste tree Vitex agnus-castus Dong quai Angelica sinesis Antidepressant St John’s Wort Hypericum perforatum Schisandra Schisandra chinensis Mild Sedative Valerian Valeriana officinalis Withania (Ashwaganda) Withania somnifera Skullcap Scutellaria lateriflora Essential Fatty Acid Evening Primrose Oil Oenothera biennis provider Analgesic Willow bark Salix spp. Yellow jasmine Gelsemium sempervirens Reference for ‘Treatment goals and herbs Considered’ section: Bone, K. 2003, A Clinical Guide to Blending Liquid Herbs, Elsevier, London. Mills, S., Bone, K. 2000, Principles and Practice of Phytotherapy, Churchill Livingstone, London. Final Prescription and Treatment Recommendation Herbal Liquid Formulation 1 Vitex agnus-castus 1:2 20 mL Hypericum perforatum 1:2 25 mL Valeriana officinalis 1:2 25 mL Silybum marianum 1:1 30 mL Total 100mL Dose 5mL with water 3 times daily, for 3 menstrual cycles (Wuttke 2003:348-57). Plus 1 MediHerb Tribulus Forte tablet 3 times daily, on days 5 to 14 only of the menstrual cycle (with the start of menstruation being day 1), to be ceased upon conception (Zarkova 1982: 223-234). MediHerb Tribulus Forte is a proprietary product which contains 9.0g Tribulus terrestris extract equivalent to dry herb (aerial parts) which is standardised to contain furostanol saponins as protodioscin 110mg. Nutritional Considerations To maximize the overall health of the patient and encourage conception, avoidance of tea, coffee, alcohol, smoking and any drugs (recreational or prescription), as well as a diet comprising mainly of unprocessed foods where beer is abstained from is advised. Beer causes an increase prolactin levels (Wuttke 2003:348-57). Table of Medicinal Plant Parts and Key Constituents Name of Herb Plant part Key Constituents relevant to this case Used Vitex agnus-castus Fruit (berries) the diterpene rotundifuran found in the essential oil which also contains monoterpenes, sesquiterpenes, flavonoids, iridoids glycosides (including aucubin, agnuside). Tribulus terrestris Herb (aerial furostanol (steroidal) saponins as parts) protodioscin Hypericum perforatum aerial parts Hypericin (H) and pseudohypericin (PH) –napthrodianthrones (0.05-0.6%), flavonoids, phenolics including hyperforin, procyanidins and essential oil. H and PH are collectively called total hypericin (TH). Valeriana officinalis root, rhizome Valepotriates –iridoids 0.5 - 2%, essential oil 0.35 to 1%, non-volatile cyclopentane sesquiterpenes (valerenic acid and its derivatives), amino acids, lignans Silybum marianum fruit Silymarin (comprised of silybin, silychristin and silydianin) – flavanolignans Table Reference: Mills, S., Bone, K. 2000, Principles and Practice of Phytotherapy, Churchill Livingstone, London. Rationale for Herb Selection The female reproductive system presents to modern medicine, one of its greatest challenges (Low 2009 58-8). Despite the technology available and the advances made, many women are dissatisfied with the current procedures, that are often surgical and lacking in a holistic approach and favourable outcomes (Low 2009 58-8). As a result, increasing numbers of women (up to 45%) are turning to herbal medicine, not only seeking better outcomes, but also to gain more personal input into their reproductive health (Low 2009 58-8) (Huang 2008:211-5). There is, however, a particular lack of quality scientific and clinically relevant data, leading phytotherapy practitioners to be guided by some useful clinical trials and case evidence for the remainder when treating women for reproductive concerns (Low 2009:54-8) (Huang 2008:211-5). In terms of pregnancy Mills and Bone state (2000:246) that there is a professional reluctance to prescribe herbs during pregnancy, again, likely due to the limited amount of clinically relevant data at present (Low 2009:54-8), but that nevertheless herbs such as Zingiber (ginger), Vitex (chaste berry) and Rubus idaeus (raspberry leaf) have been used on a traditional basis (Felter: 1905) during the trimesters of pregnancy (Harefuah 2006:738-42). Phytotherapy seems to be well suited to treatment of the female reproductive system, due to its ability to be applied subtly. Mills and Bone (2000:238-240) suggest the tendency to self - correction of this system, when provided with a light phytotherapeutic nudge. They draw parallels between the concept of self- organization in the female reproductive system and its consistency with other complex biological systems, including its rythmicity (Mills 2000:238-240). The approach used towards the female reproductive system here utilizes these concepts in an attempt to prompt the body to return to its original program and normalise ovarian- pituitary communication and rythmicity.