This large cohort study1 confirms the findings from the Women’s Health Initiative (WHI) (2,3) that current users of estrogen plus progestogen (EPT) are at an increased risk of invasive breast cancer (RR 2.0). This study also confirms prior observational studies4 that estrogen therapy alone (ET) increases the risk of breast cancer (RR1.30).

Over one million women (1,084,110) ages 50 to 64 years (average age 55.9 years) who were initially cancer-free were followed from 1996 to 2001 in a national screening program. Mean follow-up was 2.6 years for breast cancer incidence and 4.1 years for mortality. Primary endpoints of the study were diagnosis of breast cancer and deaths from breast cancer. Overall, current use of ET/EPT (Estrogen therapy/Estrogen and Progesterone therapy) was associated with a statistically significant increased risk of breast cancer incidence (RR 1.66; 95% CI 1.58-1.75) and breast cancer mortality (RR 1.22; 95% CI 1.00-1.48) compared to nonusers. Past use did not increase the risk of incidence or mortality and the risk of breast cancer decreased with time since last use. Current users of estrogen plus progestogen were at the highest increased risk (RR 2.0; 95% CI 1.88-2.12) of invasive breast cancer, compared to current ET users (RR1.30; 95%CI 1.21-1.40). In current users of each type of HRT, the risk of breast cancer increased with duration of HRT use. This risk appeared to be linear over time and was less in heavier women. In women with a BMI > 25, the relative risk of breast cancer for all users of HRT was 1.46 versus 1.97 for those with a BMI < 25. Of note, vaginal or other local EPT formulations did not increase the risk (RR 0.67; 95% CI 0.30-1.49). No significant differences in risk were found between specific types or doses or regimens of systemic ET or EPT. However, breast cancer risk increased as duration of use increased.

Although this study is observational, the results are very similar to those of the WHI and the results predicted by the Collaborative Group on Hormonal Factors in Breast Cancer Study4, which lends credence to these findings. Prior observational studies have suggested that ET alone increases the risk of breast cancer (RR 1.3). Ten years of HRT with ET alone is estimated to result in five (95% CI 3-7) additional breast cancers per 1000 women, and EPT combination to result in 19 (95% CI 15-23) additional cancers per 1000 women.

Evaluating a broader range of hormone therapy products than the WHI (which examined just one specific type of estrogen and progestogen, conjugated equine estrogen plus medroxyprogesterone acetate), the Million Women Study found very little variation between specific estrogen and progestogen products, their doses, their routes of administration, or whether the regimen was continuous or sequential. For estrogen-only users, increased risk was seen with oral, transdermal, or implanted formulations. No increased risk was seen with vaginal or local estrogen preparations. Progestogen only preparations were associated with an increased risk, but based on only nine incident breast cancers. Tibolone was also found to increase breast cancer risk, but less than combined EPT.

On an absolute basis, the breast cancer risk from ET is not very high. Many physicians are awaiting the results of the estrogen alone arm of the WHI to determine if estrogens in the absence of a progestin also increase the risk of breast cancer. However, a calculation of expected breast cancer incidence rates in the ongoing WHI ET arm estimates that there would be 70 new breast cancer cases in the women taking placebo and 78 in those taking estrogen alone. Thus, the WHI trial may not have sufficient statistical power (i.e., enough women in the study) to detect the slightly increased relative risk seen in the Million Women Study.

In this study, the follow-up was 2.6 years for cancer incidence and 4.1 for mortality. The increased risk in breast cancer became apparent within 1 to 2 years of starting treatment, irrespective of type of hormone therapy used. Once hormone therapy was stopped, the risk began to decline, and by 5 years reached the same level as never users. Increased mortality was seen, but it was of borderline statistical significance. Longer follow-up is needed from this study and the WHI to determine any effects on mortality from breast cancer.

They went back to natural estrogen, a cumbersome and expensive product, harvested from the urine of pregnant mares. The mares are fitted with a collection cup attached to a hose and confined in a narrow stall for the entire eleven months of their pregnancy. As soon as possible after the birth of their foals, who are routinely slaughtered, the mares are re-impregnated and the urine-collection process begins again.

If the pharmaceutical companies were to get women hooked the best time was at menopause when they were in estrogen withdrawal and begging for a fix. At least that was what the researchers thought that hot flushes, joint pains, sleeplessness, etc., added up to. The new mixtures were the methadone rather than the heroin. For some reason the women did not stay hooked. The selling and the product design were relaunched time and again. Sub-dermal implants seemed to lose their effectiveness; women required bigger closes, the implants became ineffective more quickly, menopausal symptoms recurred at shortening intervals. The manufacturers of sex steroid preparations, like the manufacturers of cigarettes, had what they wanted, addiction, and they were just as unwilling to talk about it. An underground network of pushers w-as set up; women, all users themselves, held HRT parties, bring-and-buy sales and coffee mornings, to spread awareness so that women would ask their doctors to prescribe.

Women who take estrogen definitely tend to look younger than their years. Their skin remains smoother, moister, oilier and more flexible – in other words younger. That doesn’t mean you should take estrogen for cosmetic purposes alone. Younger-looking skin is just one of the magical consequences of HRT that researchers have been unable to substantiate; as far as laboratory investigations can establish, exogenous estrogen has no effect on the epidermis or supporting structures.