Jewish World Review Jan. 4, 2002 / 20 Teves, 5762

Vitamin a & the risk of hip fracture in postmenopausal women

By Robert A. Wascher, M.D., F.A.C.S.

http://www.NewsAndOpinion.com -- THIS week's Journal of the American Medical Association leads off with a study of the effects of Vitamin A on the risk of hip fractures in postmenopausal women. A total of 72,337 postmenopausal women, aged 34 to 77 years, were followed for 18 years (all study participants were enrolled in the ongoing Nurses' Health Study). Using a food intake questionnaire, the study analyzed the intake of Vitamin A in these women, and then assessed for the incidence of hip fractures.

This study found a roughly 50% increase in the incidence of hip fractures among the women with the highest intake of Vitamin A (3,000 ug/day of retinol equivalents) when compared to women with the lowest level of Vitamin A in their diets. In women with a high intake of Vitamin A, the increased risk of hip fracture was somewhat reduced if they were also on estrogen hormone replacement therapy for menopause. The Vitamin A precursor, beta-carotene, did not significantly increase the risk of hip fracture, however. The study's authors concluded that women with a high daily intake of Vitamin A may be at increased risk of developing osteoporotic hip fractures.

As pointed out in the accompanying editorial, the results of this study require further evaluation before its conclusions can be fully accepted. The biological effects of Vitamin A are profound, as it is involved in the regulation of vision, cell growth and reproduction, and immune function. Vitamin A deficiency can, therefore, have profound effects on health. Vitamin A deficiency during childhood can cause growth retardation, and in severe cases of deficiency during childhood, may even be fatal. The retina requires Vitamin A for vision in low levels of light. Thus, a deficiency of this vitamin causes a loss of vision at night and under other low-light conditions. Abnormalities of the lungs, gastrointestinal tract and urinary tract may also occur with Vitamin A deficiency. In severe cases of Vitamin A deficiency, the immune system may become compromised, rendering the patient highly susceptible to infection.

Vitamin A occurs rarely in our diets, although it is particularly rich in liver. Eggs and whole-milk products also contain significant concentrations of Vitamin A, though much less than is found in liver. Of course, many vitamin and food supplements contain added Vitamin A, as well as its precursor, beta-carotene. Foods rich in beta-carotene (which does not appear to increase the risk of hip fracture) include carrots, tomatoes, green leafy vegetables, and orange-colored melons and peppers. Also, with respect to the selection of postmenopausal women for this study, it is known that the blood levels of Vitamin A gradually increase as we age.

There are a number of intriguing contradictions and unanswered questions with respect to this study's conclusions. However, it is probably prudent to observe the current guidelines for Vitamin A intake (and more so the active form of Vitamin A, rather than the nontoxic precursor, beta-carotene) until further data becomes available: 800 ug/day for men and 700 ug/day for women, with an absolute upper limit of 3,000 ug/day for men and women.

OVARIAN CANCER RISK AND ORAL CONTRACEPTIVES

Ovarian cancer is a relatively uncommon disease, but it is estimated to afflict 1 in every 70 women in the United States. Approximately 24,000 women will develop ovarian cancer in the US this year, and more than 14,000 will die of the disease. The diagnosis of ovarian cancer is complicated by the fact that the disease usually produces few-if any-symptoms during its early stages. Non-specific discomfort in the lower abdomen, fullness after eating or "heartburn," and gradual enlargement of the abdomen may be the only symptoms of ovarian cancer before it spreads outside of the ovary. Indeed, close to 80% of patients with ovarian cancer are not diagnosed until the disease becomes advanced.

Several studies over the past 5 years have reported on the apparent protective effects of oral contraceptive pills (OCPs) against ovarian cancer. However, the basis for this association has not been well understood. This week's Journal of the National Cancer Institute features an interesting study that corroborates prior research on this subject, and also suggests an explanation as well. The study looked at 390 patients with a history of ovarian cancer, and compared them with 2,865 "control subjects" who did not have a history of ovarian cancer.

The results of the study strongly suggest that it is the hormone progesterone in OCPs that confers this protective effect on the ovaries. Most OCPs contain a combination of two female hormones: estrogen and progesterone. When taken together, they essentially shutdown the normal hormonal function of a woman's ovaries, including ovulation. In this study, women taking OCPs with a low dose of progesterone had slightly more than twice the risk of developing ovarian cancer when compared to women taking OCPs with higher doses of progesterone. The estrogen content of the OCP appeared to have no effect on the risk of ovarian cancer, however. Importantly, this effect was seen even after a relatively short duration of OCP usage.

This data adds to previous research that appears to show a 30% to 50% reduction in the incidence of ovarian cancer among women taking combination OCPs for three or more years. Previous studies, however, did not characterize which factors in OCP formulations are responsible for this protective effect. An very important point to note is that the patients studied in this trial were actually part of a much older study of the effects of OCPs.

Significantly, the OCPs taken by the study's participants, some 20 years ago, contained substantially higher concentrations of both estrogen and progesterone than today's OCPs. Based upon the findings of this study, today's "mini-dose" combination OCPs may not be as protective against ovarian cancer as the OCPs that were assessed in this study.

This consideration mandates that a similar study be repeated using modern OCPs, and will require many years before useful results become available. It is also important to remember why OCP manufacturers have reduced the hormone content of their products. Large doses of these hormones, as contained in earlier preparations, have been associated with an increased risk of breast and uterine cancer, blood clots in the legs and lungs, and stroke, as well as other less serious side effects.

Moreover, recent findings have called into question the previous belief that supplemental estrogen reduces the risk of heart disease in women. Still, this is an important study to know about, and it will form an important basis against which to compare the results of similar future studies.

JWR contributor Dr. Robert A. Wascher is a senior research fellow in molecular & surgical oncology at the John Wayne Cancer Institute in Santa Monica, CA. Comment by clicking here.