Can HRT combat menopause?

There is a new storm howling through the ranks of doctors who still tremble at the thought of prescribing hormones to resist the relentless march of ageing. After the Women’s Health Initiative trial, which questioned the wisdom of using hormones to prevent those diseases that escalate with ageing, such as Alzheimer’s dementia and heart disease, an American anthropologist is threatening to turn the anti-ageing landscape on its head by daring to suggest that women need hormones, lots of them, and they need to be taking them for a long, long time.

Protective menstruation
I first met T.S. Wiley, who champions the cause of high-dose hormone replacement therapy, at an anti-ageing conference in Monaco during the early stages of 2010 and it was difficult not to be overawed by her swashbuckling swagger. Wiley’s central thesis is that young women don’t get breast cancer because of the rhythm and amplitude of hormones produced during the normal menstrual cycle. It is also this pattern of hormone production with oestrogen, the major female hormone, hitting its peak during mid-cycle, which then switches on progesterone activity, in turn reaching its crescendo during the latter part of the cycle, which sees to it that cells undergo their normal trajectory of growth, maturation, elimination and regeneration.

Wiley claims that this healthy young pattern of cyclical activity can be revisited by the ageing female to not only regenerate vital brain cells and preserve strong bones but also to prevent what women fear most when taking hormones: the threat of breast cancer.

Reproducing reproductive patterns
While high doses of oestrogen makes cells multiply, peak production of this hormone, which is reached during mid-cycle, ignites progesterone, encouraging cells to self-destruct. What women need, according to Wiley, is rising amounts of oestrogen to propel progesterone into getting rid of cancer cells.

Wiley’s point is that, rather than give women low doses of natural hormones, which is what most of us have been doing, thinking this is the safest way to provide the benefits of hormones without any downside, especially the possibility of causing cancer, what we really have to do is re-create the normal peaks and troughs of hormone production typical of a young female if we wish to maintain youthfulness and minimise cancer risk.

Wiley states that our preoccupation with synthetic versus natural, bioidentical and supposedly safe hormone replacement is missing the point. Natural and bioidentical are no less safe than synthetic hormones, derived from horse urine, if not administered according to the sequential cadences of a young woman. At least, that is the way Wiley sees it.
Weighing the evidence

What any innovator worth their salt needs to do to verify their position is carry out a scientific experiment that proves what they are saying is true.  Wiley does not have a clinical trial that would have any credibility in the eyes of the scientific community but what she does have is a large cohort of ageing women who have been taking the doses of hormones that mimic those of much younger women during a typical menstrual cycle and all are thriving, reports Wiley. She also has a collection of breast cancer sufferers who are taking hormones in a similar fashion and, according to Wiley, are all doing well.

Given the complex way in which genes determine the way each individual woman responds to hormones, scientists around the globe are somewhat baffled by the way the Wiley women have so favourably responded to this regimen.

Leon Speroff, a professor of obstetrics and gynaecology at Oregon Health & Sciences University in the USA and author of a massive tome entitled Clinical Gynecologic, Endocrinology and Infertility, considered the bible for all those interested in female health, indicates that the high doses of oestrogen suggested by Wiley to get progesterone to step up to the plate in order to rid the body of faulty DNA and damaged cells could perhaps be much lower than her calculations.

John Eden, Associate Professor of Reproductive Endocrinology at the University of New South Wales, reframes the whole picture of hormone replacement and its effects on the female breast with the evidence that what has a much larger impact on the breast is not the hormones given to a woman, but the hormones her own breast manufactures.

Breast-made hormones
Oestrogen is made in the breast by the activity of enzymes such as aromatase, sulphatase and 17beta-dehydrogenase type-1, which become much more operational after menopause. It is also the oestrogen metabolites or byproducts that can induce DNA damage with test-tube evidence that the 2- and 4–hydroxyoestrogen metabolites were able to coax benign fibrocystic breast cells into becoming cancerous cells.

While stress and being overweight can switch on aromatase, breast cells can be protected by an adequate supply of B vitamins and the mineral iodine, which can be lacking in many women, together with a healthy supply of organic broccoli free of pesticides. Eden suggests hormone replacement therapy in the form of oestrogen may actually be beneficial by limiting the actions of aromatase and sulphatase, the oestrogen-manufacturing enzymes.

Protective progesterone?
As far as progesterone is concerned, although the claims are strong for this hormone being entirely cancer-protective by encouraging cancer cells to self-destruct, there is at least some evidence that, while not initiating the development of breast cancer, progesterone can encourage pre-existing cancer cells to multiply. Research conducted at Charles Sturt University in Wagga Wagga shows that breast cancer cells have a progesterone receptor and that this is a complex structure also containing what has been called a progesterone receptor membrane component 1 (PGRMC1).

What PGRMC1 does is stimulate cancer cell growth when switched on by progesterone. Therefore, progesterone might be able to get rid of cancer cells but it might also be able to promote cancer cell growth.
As much as Wiley is cooking up a storm, it may be prudent to defer to the wisdom of professor Speroff, who reminds us that “the breast response is complex, involving many growth factors and many hormones”, making the issue of hormone replacement rife with ongoing debate.