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Without doubt, the most popular use for EPO supplements is conditions relating to the female reproductive system.

Premenstrual syndrome Interest in EPO supplements as a potential treatment for PMS began in the early 1980s, largely as a result of investigational work published by David Horrobin. In the Journal of Reproductive Medicine be reported on positive results obtained in three double-blind placebo-controlled studies and two open trials in women with premenstrual syndrome (Horrobin 1983).

Shortly afterwards, results from a study conducted by Brush et al provided a rationale for considering EPO supplementation for PMS. This study found that levels of LA in the phospholipids of women with PMS were significantly above normal, yet the concentrations of all metabolites were significantly reduced (Brush et al 1984). Based on these findings, researchers suggested that some women with PMS may not be able to adequately convert LA to GLA and as a result, sensitivity to luteal phase prolactin and steroids may be increased. As such, supplementation directly with GLA (found in EPO oil) would bypass the problem and potentially normalise sensitivity and result in reduced symptoms.

For a time, these results stood unquestioned, until in 1990 another double-blind placebo-controlled trial involving 38 women failed to show evidence of efficacy over six cycles (Khoo et al 1990).

A comprehensive review published in 1996 identified seven placebo-controlled trials, although in two the randomisation was not clearly indicated. The two most well controlled studies failed to detect a benefit for EPO supplements; however, as they were small, modest benefits cannot be excluded (Budeiri et al 1996). Interestingly, in one of these studies the only significant benefit noted by subjects was a mild reduction in breast pain.

Mastalgia An early review on treatments for mastalgia produced by the Cardiff Evening primrose oil 396

Mastalgia Clinic concluded that danazol was the most effective drug treatment, with

bromocriptine and EPO having equivalent efficacy. Additionally, they state that patients treated with EPO reported much fewer adverse events than those using danazol or bromocriptine (Gateley et al 1992a). Interestingly, treatment with EPO was found to improve the fatty acid profiles towards normal, although this was not always associated with a clinical response (Gateley et al 1992b).

A more recent 6-month, randomised double-blind trial did not find that EPO, EPA or a combination of the two were significantly better than placebo in reducing the symptoms of mastalgia. Corn oil and corn oil with wheatgerm oil were used as control oils. The decrease in days with pain was 12.3% for EPO and 13.8% for its control oil; the decrease in days with pain was 1 5.5% for fish oil and 10.6% for its control oil (Blommers et al 2002).

Evening primrose oil has also been assessed for its ability in preventing fibroadenomas. A small study of 21 patients found that EPO had no significant influence over the natural history of breast fibro-adenomas (Kollias et al 2000). A more recent study has also yielded negative results when compared with topical NSAIDs, with significantly reduced efficacy, more reported adverse effects and ratings of less acceptability by the patients (Quereshi & Sultan 2005).

Endometriosis A combination of GLA and EPA is better than placebo in relieving the symptoms of endometriosis according to one placebo-controlled study. Of those in the treatment group, 90% reported relief of symptoms compared with 10% of those in the placebo group (Horrobin 1990).

Oedema and hypertension during pregnancy In a partially double-blind, placebo-controlled clinical trial, a combination of EPO, fish oil and magnesium oxide was found to be superior to placebo in lowering the incidence of oedema (P = 0.004) in pregnant women. Significantly fewer women developed hypertension in the group receiving the oils and magnesium oxide. The three cases of eclampsia all occurred in the control group (D'Almeida et al 1992).

Menopausal hot flushes According to one randomised, double-blind placebo-controlled study EPO supplementation significantly reduces the maximum number of night-time flushes, although other symptoms failed to respond. The study used a dose of four capsules daily (each containing 500 mg EPO and 10 mg vitamin E) over 6 months (Chenoy et al 1994).

A position statement of the North American Menopause Society (2004) concluded that evidence was lacking to warrant the use of EPO in the treatment of vasomotor symptoms of menopause.

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