Individualizing therapy

Schiff: We have talked about what hormones do and don’t do. Now let’s think back to the patient who has decided she’s going to start HRT. How do you decide which option to prescribe and how do you encourage adherence?

Berga: You have to think about each person individually, and that takes an enormous amount of time. However, the way I look at it is that you don’t give any important hormones, such as thyroxine or insulin, without a great deal of dose titration and adjustment. That should be true for HRT as well.

The concept here is quality of life. In some ways it’s like an addiction model: If patients feel better on the regimen you prescribe, they’ll follow your advice and continue their tablets or patches. If they’re feeling worse, either they’re not going to come back to you or they’re going to come back and be unhappy. There’s no magic answer for everyone. The main message is that you have to be a good clinician, you have to be available when the patient needs input, and you have to tailor therapy. To do that, you need to be aware of all the alternatives and their advantages and disadvantages.

Schiff: So if we’re going to treat patients, we have to treat them with something that they can tolerate well, that has few or no side effects, that is effective, and that is likely to be continued. Dr. Nachtigall, how do you make that selection with your patients?

Nachtigall: I agree totally with Dr. Berga that it’s a trial-and-error process and that you have to let the patient know you may not get it right the first time. You also have to anticipate some of the nuisance side effects, such as breast tenderness, and let the patient know that those side effects may occur but are not serious. You simply tell her, “Let me know if you have them, and I will fix them.”

As we’ve discussed, changing the dose or the progestin may get rid of problems like bleeding or breast tenderness. Sometimes patience and time will take care of them. The important thing is to make sure the patient knows you’re addressing her problems and that she isn’t getting cancer. You need to let her know it’s all right to call and tell you that everything’s not going perfectly. What you want to avoid is having her stop calling you, stop her therapy, and never come back. You have to deal with the negative but stress the positive.

For example, when I see a woman who had vaginal atrophy that estrogen has reversed, I say, “Your vagina looks all better. How do you feel?” I remind her that there has been a change for the good. Bone density measurements are also a wonderful motivator because they’re real and they’re on paper.

Schiff: But how in the first place do you select the kind of treatment to provide? How do you decide on continuous combined versus sequential therapy, for example?

Nachtigall: I’m guided by the patients and what they want. About 90% of them don’t want periods, but there are some who do. It makes them feel younger, perhaps—or they think they’re cleaning out the uterus because somebody once told them that. For those few, I’m happy to provide sequential therapy, but most women are happier with a continuous combined product.

Schiff: Dr. Sarrel, do any of your patients prefer cyclic hormones?

Sarrel: As Dr. Nachtigall said, there’s a subgroup, mostly younger women, who have a preference for cycling. In their minds, a woman who has no periods is either pregnant or old. I give them estrogen every day and add a progestin for 12 days each month. They have some bleeding from the 11th to the 15th of the month, but it’s been very rare in my experience for these women to discontinue because of that light scheduled bleeding that they can plan around. However, by the time they’re in their mid- to late 50s, their preference shifts to hormone replacement without bleeding.

The majority of women prefer the continuous combined method, with no flow at all, from the very beginning. The only problem is the irregular breakthrough bleeding that can occur and that women find very objectionable. Nobody likes that kind of surprise. Postmenopausal women today are involved in work or are on the go all day long, and sudden bleeding is disruptive. That’s a big problem for continuance, so for most women, amenorrhea is certainly the goal.

Schiff: And what about the choice of components?

Sarrel: In the choice of an estrogen, from the vascular studies that I’ve done, I have a preference for products with good systemic absorption that maintain steady blood levels around the clock. That’s not true for all estrogens.

Transdermal delivery of estradiol is known to result in a very stable blood level, but the combination of 1 mg of estradiol and 0.5 mg of NETA we discussed earlier also produces a steady blood level curve over 24 hours. That’s something I point out to my patients. I stress the importance of taking their tablets every day or changing their patch as directed so that blood levels of estrogen are maintained at optimal levels for optimal effectiveness.

Schiff: Dr. Berga, what’s your approach in deciding which estrogen to use?

Berga: For the brain, studies show clearly that results are going to be better if both the ER and ERß are occupied. I think most true estrogens will do that, but I have concerns about effects of SERMs and phytoestrogens on the CNS. Estradiol binds the best to both ER and ERß—100% to each. It’s the physiologic ligand for both kinds of estrogen receptors.

The real challenge in my mind is finding a product that’s not cumbersome to administer. So, like Dr. Nachtigall, I’m guided by the patients. I ask them if they find it easier to take a pill every day or apply a patch once or twice a week. I talk to them about bleeding and other possible side effects. I want their buy-in. Patient preference and patient participation are clearly the keys to getting adherence.

Nachtigall: A lot of women have the idea that if it’s “natural,” it’s better, and they have the perception that it’s natural if it comes from a plant. I’ll go along with that if I think it will help them continue without worrying.

Berga: As you said before, Dr. Nachtigall, if you do something every day that you’re apprehensive about—such as taking a medication you’re afraid of—the long-term health consequences of that are not benign. We want our patients to have confidence in us and the therapy we’ve agreed upon.