Herbal medicine for the management of polycystic ovary syndrome (PCOS) and associated oligo/amenorrhoea and hyperandrogenism; a review of the laboratory evidence for effects with corroborative clinical findings. Studies excluded from this review. The aim of this review was to synthesise the pre-clinical and clinical evidence explaining the mechanism of effect for herbal medicines in PCOS and associated oligo/amenorrhoea and hyperandrogenism. Clinical studies investigating herbal medicines were excluded based on the absence of evidence for a mechanism of effect in oligo/amenorrhoea, hyperandrogenism and PCOS (Table 3) and or investigation of incomplete herbal extracts (isolated herbal chemicals) (Table 5) or the absence of clinical data corroborating mechanism of effects (Table 4). Table 3. Herbal medicines excluded from this review for which there was clinical evidence for effect but no pre-clinical evidence demonstrating mechanism for effect and/or evidence for the specified clinical conditions. Herbal medicine Clinical evidence (or potential) for PCOS and associated oligo/amenorrhoea or hyperandrogenism Reason for non-inclusion – insufficient pre-clinical evidence for mechanism of effects for whole herbal extract Camellia sinensis (green tea) Hormone concentration in obese women with PCOS [1]. Mentha spicata (spearmint tea) Lowered testosterone in women with PCOS [3, 4]. Ginkgo Biloba (ginkgo) Metabolic hormone management in type two diabetes [5]. Grifola frondosa (miatake mushroom) Linum usitatissimum (flax seed) Ovulation rates in PCOS [6]. Isolated constituent (epigallocatechin gallate 1) examined [2]. No evidence found for effects for whole herbal extract in PCOS, oligo/amenorrhoea and hyperandrogenism. No evidence for mechanism of effect found for PCOS, oligo/amenorrhoea or hyperandrogenism. No evidence for mechanism of effect in PCOS, oligo/amenorrhoea or hyperandrogenism found. No evidence for mechanism of effect in PCOS, oligo/amenorrhoea or PCOS revealed. No mechanism of effect in PCOS, oligo/amenorrhoea or hyperandrogenism found. No evidence for mechanism of effect found in PCOS, oligo/amenorrhoea or hyperandrogenism (in female cell cultures or animals). No mechanism of effect in PCOS, oligo/amenorrhoea or hyperandrogenism (in female cell cultures or animals). No mechanism of effect in PCOS, oligo/amenorrhoea or hyperandrogenism. No mechanism of effect studies found different clinical outcome to those specified. Pygeum africanum (pygeum) Menstrual regulation [7, 8] and hormonal concentration [8-10] in post-menopausal women. Anti-androgen effects in prostatic hypertrophy [11]. Serrenoa repens (saw palmetto) Anti-androgen effects in chronic pelvic pain and prostatitis [12-14]. Silybum marianum (St Mary’s thistle) Stachys lavandulifolia (wood betony) Fatty liver disease in type two diabetes [15]. Compared with progesterone supplementation for dysfunctional uterine bleeding in women with PCOS [16]. Anti-androgen effects in women [17]. Urtica dioca (nettle root) Anti-androgen effects through interaction with SHBG in prostate cells [18-20]. Antiinflammatory and anti-nociceptive effects[21] No evidence for effects of Urtica dioca in female cell cultures or animals. Other excluded studies investigated the herbal medicines included in this review examining conditions other than PCOS, oligo/amenorrhoea and hyperandrogenism. These included investigations into effectiveness for Vitex agnus-castus for pre-menstrual syndrome [22-27]and mastalgia [28, 29], Cimicifuga racemosa for menopausal symptoms [30]and Glycorrhiza spp with Paeonia lactiflora libido in males [31]. Clinical studies examining the effectiveness of complex herbal formulas for PCOS and associated oligo/amenorrhoea and hyperandrogenism, without demonstration of a mechanism of effect for the whole complex formula were also excluded as were studies investigating complex formulae for different outcomes (PMS, endometriosis etc ). Table 4. Herbal medicines with pre-clinical evidence in PCOS, oligo/amenorrhoea and hyperandrogenism without clinical evidence for effectiveness. Herbal medicine Curcuma longa (turmeric) Pre-clinical evidence for (potential) effects in reproductive endocrinology in PCOS and associated oligo/amenorrhoea and hyperandrogenism Anti-androgen effects [32]. Reason for exclusion No clinical evidence examining effectiveness in women was found. No clinical data found. Matricaria Reduced luteinising hormone and chamomilla improved ovarian morphology in animals (Chamomile) with PCOS [33]. Mentha piperita Anti-androgen effects in animals [34]. No clinical data for women. (peppermint) Silybum marianum Anti-proliferative antioxidant and No clinical evidence including (St Marys thistle biochemical effects in the liver [35]. women was found. Studies investigating chemical compounds derived from the herbal medicines, included in this review but investigating different outcomes were found for Vitex agnus-castus [36] and Cimicifuga racemosa [37]. Table 5. Studies excluded due to the investigation of chemicals isolated from herbal medicines. Isolated chemicals Phytoestrogens Berberine Catechin derived from Camellia sinensis Sapponins (derived from Tribulus terrestris) Paeoniflorin, glycyrrhizin and glycyrrhetic acid Evidence for effects Hormonal effects in ovarian granulosa cells [38]. Comparison with metformin in PCOS [39]; ovarian theca cell hormone production [40]. Effects of epigallocatechin gallate 1 on cellular metabolic endocrinology [2]. Effects on reproductive endocrinology [41]. Ovarian androgen production [42]. 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