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CLINICAL REVIEW: Adam H Balen and Anthony J Rutherford Managing anovulatory infertility and polycystic ovary syndrome BMJ 2007; 335: 663-666 [Full text]

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Management of anovulatory infertility and polycystic ovary syndrome should include diagnosis and treatment of essential nutrient deficiencies.

Ellen C G Grant   (1 October 2007)

Management of anovulatory infertility and polycystic ovary syndrome should include diagnosis and treatment of essential nutrient deficiencies. 1 October 2007
Ellen C G Grant, physician and medical gynaecologist Kingston-upon-Thames, KT2 7JU Send response to journal: Re: Management of anovulatory infertility and polycystic ovary syndrome should include diagnosis and treatment of essential nutrient deficiencies.	Professor Adam Balen’s review of the management of polycystic ovary syndrome (PCOS) is informative. 40-50% of women with PCOS are overweight and insulin resistance is seen in 20-40% of obese women and 10-15% of slim women. Clomifene and gonadotrophins can cause superovulation and a potentially life threatening hyperstimulation syndrome. Trials of the insulin sensitizing agent metaformin disappointed with a high miscarriage rate. Menstrual cycles in obese women were more safely restored by weight loss.1 What, however, are the fundamental causes of PCOS? An important clue is the association with eating disorders (anorexia or obesity) which suggests nutritional deficiencies or imbalances. 20 - 25% of white women have PCOS in the UK, a country where most women have taken contraceptive pills before pregnancy. Past users had a significantly increased risk of ovarian cysts and increasing trend with longer use in one large study.2 Women with PCOS have a high incidence of insulin resistance, glucose intolerance, obesity, hypertension, diabetes mellitus and cardiovascular disease - conditions known to be increased by contraceptive pills. Progesterone and oestrogen use can cause zinc and magnesium deficiencies, raise copper levels and reduce copper stores.3,4 South Asian immigrants to the UK have a prevalence of PCOS up to 52%. Vitamin D deficiency is known to be a factor in the causation of PCOS along with calcium dysregulation.5,6 It has been repeatedly shown that a low serum ionized magnesium and a high ionized calcium to magnesium ratio is often associated with insulin resistance, cardiovascular problems, diabetes mellitus and hypertension. A significantly lower serum Mg2+ and total magnesium and a significantly higher serum Ca2+/Mg2+ ratio has been found in PCOS patients compared with controls.7 Also a decreased total antioxidant status and increased oxidative stress in women with PCOS may contribute to the risk of cardiovascular disease.8 There are numerous references in PubMed to essential nutrients and “insulin resistance” - magnesium 190, zinc 66, copper 25, chromium 87, selenium 18, manganese 11, vitamin D 90, vitamin B 264, folic acid 44, and also references to insulin resistance and fish oils. There may have been a worrying increase in deficiencies of essential fatty acids in recent years.9 Professor Balen and I agree that there is a need to optimize health of all women before fertility treatment to prevent adverse effects for mothers and children. Unfortunately, in my experience of assessing the nutritional status of preconception couples over 30 years, many couples have endured repeated and unsuccessful fertility treatments before their deficiencies have been diagnosed. Repletion may enable couples to conceive naturally and make drug treatment unnecessary. I think that it is unethical to stimulate ovaries in nutritionally deficient women, whether slim or obese. It is possible to measure micronutrient mineral levels accurately to parts per billion. This is not minutiae but “Big Print Medicine”. 1 Balen AH, Rutherford AJ. Managing anovulatory infertility and polycystic ovary syndrome. BMJ 2007; 335:608-11. 2 Ramcharan S, Pellegrin FA, Ray R, Hsu J-P. TheWalnut Creek Contraceptive Drug Study. A prospective study of the side effects of oral contraceptives. Center for Population Research Monograph Vol 111, Maryland, USA 1981, pp 162. 3 Grant ECG. The pill, hormone replacement therapy, vascular and mood over-reactivity and mineral imbalance. J Nutr Environ Med 1998; 8:105 -116. 4 Grant ECG. Nutritional supplements to prevent pregnancy complications. http://bmj.com/cgi/eletters/329/7458/152#67502, 16 Jul 2004 5 Hahn S, Haselhorst U, Tan S, Quadbeck B, Schmidt M, Roesler S, Kimmig R, Mann K, Janssen OE. Low serum 25-hydroxyvitamin D concentrations are associated with insulin resistance and obesity in women with polycystic ovary syndrome. Exp Clin Endocrinol Diabetes 2006;114 :577-83. 6 Thys-Jacobs S, Donovan D, Papadopoulos A, Sarrel P, Bilezikian JP. Vitamin D and calcium dysregulation in the polycystic ovarian syndrome. Steroids 1999; 64:430-5. 7 Muneyyirci-Delale O, Nacharaju VL, Dalloul M, Jalou S, Rahman M, Altura BM, Altura BT. Divalent cations in women with PCOS: implications for cardiovascular disease. Gynecol Endocrinol 2001;5:198-201. 8 Houstis N, Rosen ED, Lander ES. Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature 2006;440:944- 8. 9 Grant ECG. Re: Measuring Fatty Acids - Possible increases in omega -3 and omega-6 deficiencies among women. http://bmj.com/cgi/eletters/330/7498/991#108033, 27 May 2005 Competing interests: None declared