Hormone Replacement Therapy (HRT) and Osteoporosis: What Should I Do Now?

The headline news that the estrogen-progestin arm of the Women's Health Initiative (WHI) was being halted because side effects were outweighing benefits has had many women upset.¹

But there's no need to panic. Much of the news was not indeed "new" - and the risks identified are very small. Thus, your physician may have already taken much of this information into consideration when making recommendations to you. Nonetheless, it may be time to reconsider your decisions.

Keep in mind that you should not stop taking estrogen, or any other medication, without consulting your physician. If you do decide to discontinue it, your doctor may recommend tapering (discussed below) rather than abrupt discontinuation.

The Evidence - Old and New

The original theory of estrogen replacement sounded logical. Replacement of estrogen lost after menopause certainly eased initial symptoms such as hot flashes. Clinical research also showed that it helped prevent the bone loss that can lead to osteoporosis. Epidemiological studies - which simply "count heads" in the general population, i.e. who takes what medication and what illnesses do they get - also suggested that estrogen might account for women's later-than-male development of cardiovascular disease; however, this had not been tested in clinical trials.

The first serious "wake-up" call came with the results of the Heart and Estrogen/progestin Replacement Study (HERS) in 1998.² It suggested that hormone replacement therapy (HRT) might have no benefit in preventing cardiovascular events in post-menopausal women with underlying heart disease - and might even be detrimental. Thus, physicians came up with a new theory to explain those epidemiological studies: women in the general population who used HRT were different from non-users of estrogen - they had better health habits and different risk profiles, which accounted for their lower heart disease rates in epidemiologic studies.

Further, evidence that long-term use of HRT might increase breast cancer risk slightly have also been around for years. More recently, an international panel of experts concluded that there was little evidence to support many of HRT's presumed benefits.

Now, the WHI - an NIH-sponsored study of 27,347 post-menopausal women (most of whom did not have underlying heart disease) has yielded significant results. Although the "risks" got blown up in the media into numbers that sounded terrible, here's what they really mean.

For every 10,000 "person-years," there were 7 more cardiac events in those who took HRT compared to those who did not - 8 more strokes, 8 more pulmonary emboli (blood clots in the lungs), and 8 more invasive breast cancers. Clearly, there's no reason to panic.

However, the WHI may also change the way you perceive the benefits of HRT. For example, there were only 5 fewer hip fractures per 10,000 person-years in those on HRT.

Clinical Practice at HSS

While ethics required the WHI to discontinue the trial, in view of the wide range of risk factors likely present in their nearly 30,000 enrollees, that does not mean that HRT necessarily presents serious risks to any individual patient.

The WHI news has not changed our practice at the Osteoporosis Center at the Hospital for Special Surgery. While we do not prescribe estrogen as the initial therapy for women with osteoporosis, we might consider prescribing the addition of estrogen or a SERM (raloxifine) in those who are not responding adequately to bisphosphonate therapy. (A SERM may be chosen if the patient has a family history of breast cancer.)

If a woman is already on estrogen at the time of low bone mass diagnosis, it guides our therapy because it is well documented that estrogen will reduce fractures by about 25 to 30%. Nothing further need be added if the woman chooses to stay on estrogen and continues to have osteopenia and a stable BMD (bone mineral density).

However, if a patient decides to discontinue estrogen, we can expect bone loss over the ensuing one to five years similar to the bone loss seen after menopause - from 2 to 5% per year loss of BMD. Patients who discontinue estrogen should be monitored closely for bone loss with DEXA and, perhaps, urine n-telopeptide. Patients who are osteopenic or osteoporotic probably should be prescribed another anti-resorptive agent, since bone loss will be expected when they discontinue HRT.

Talking with Your Physician

Many women have taken estrogen for years without side effects. In certain women - particularly those who are slim, healthy, and without a personal or family history of breast cancer - estrogen may be beneficial and pose little risk. However, when you have your yearly check-up, it is appropriate for you and your doctor to reassess your individual benefits and risks -- and how these may have changed over time -- and reconsider initiating or continuing use of HRT. Here's the balance sheet to keep in mind.

Estrogen Benefits

The benefits of estrogen for alleviating hot flashes and night sweats are proven. Short-term HRT probably poses little if any risk to those slim, healthy women. Even in patients whose cholesterol is controlled by a statin and whose blood pressure is well-controlled, if no previous thrombosis (blood clot) has occurred, it appears safe to take HRT for a limited period of time (up to five years) to control post-menopausal symptoms. However, this would be unwise, for example, if your mother, aunts, or sisters have had breast cancer. In such instances, your physician can recommend other approaches to reducing hot flashes.

At intervals over the years, tapering can be undertaken. For example, with Premarin dosing, under your doctor's guidance, you could be moved from .9 mg to .625 to .3 to zero over a period of months. If hot flashes recur, you can be maintained on the lowest possible dose to control symptoms.

If HRT is discontinued and vaginal dryness occurs, topical estrogen creams can alleviate atrophic vaginitis.

The bone benefits of estrogen are outlined above. Keep in mind that bisphosphonates are more potent - and SERMs less potent - than HRT in preserving bone density.

Estrogen Risks

The cardiovascular and breast cancer risks are outlined above. There is also an increased risk of formation of gallstones and cholecystitis with use of any estrogen - whether oral contraception or HRT.

Other Choices

At the Osteoporosis Center at Hospital for Special Surgery, our first choice for treating women who are osteopenic or osteoporotic is a bisphosphonate (alendronate or risedronate). They are far more effective than estrogen at reducing the risk of fracture and have a better safety profile. If the patient has a prior history of gastric ulcer or related gastric problems or cannot tolerate a bisphosphonate, we recommend a SERM (raloxifine), although SERMs also carry a risk of thromboembolism. In addition, new options are soon expected to be available.

If you have a high cholesterol level, you need a statin or other cholesterol-lowering medication to help prevent cardiovascular disease. Statins not only lower cholesterol but have been shown to reduce the risk of heart attacks.

If you are taking HRT and believe you have personal or family risks of heart disease, stroke, breast cancer, or blood clots, make an appointment to discuss your options with your physician. Even if you don't believe you have such risks, include a discussion of HRT at your next regularly scheduled check-up.

If you are participating In a clinical trial involving estrogen, again, it may be appropriate for you to discuss your individual risks with the principal investigator. Remember, you always have the right to drop out of a study.