Dr. Holly Thacker: In light of the updates that Drs. Hodis and Gass have presented on hormone therapy (HT) for menopausal women and that Drs. Jenkins and Sikon have presented on nonhormonal options for menopausal management, let’s start our roundtable by considering a couple of case studies that will give us the chance to apply the latest data in a practical way.
CASE 1: A SYMPTOMATIC 67-YEAR-OLD IN WHOM HORMONE THERAPY WAS ABRUPTLY STOPPED
Dr. Margaret McKenzie: A 67-year-old menopausal woman presents for the evaluation of hot flashes, vaginal dryness causing dyspareunia, and decreased libido. She was previously on estrogen-progestogen therapy (EPT), consisting of daily conjugated equine estrogens and medroxyprogesterone acetate, for 15 years starting at the time of natural menopause. Her gynecologist discontinued this HT abruptly at the time of the initial release of data from the Women’s Health Initiative trial, and the patient is now seeking another opinion about resuming HT. When she presents, she has been off HT for less than 6 months. Would you restart HT in this patient?
Dr. Andrea Sikon: The abrupt discontinuation certainly contributes to her symptoms. The short duration of time off HT is important, and would lead me to restart HT after an updated review of risk factors. She had been on it for 15 years and has done fine, so she appears to be an ideal candidate to restart.
Dr. McKenzie: What specific questions would you ask when doing your risk assessment? How would you evaluate this patient to determine whether she is a good candidate to continue HT?
Dr. Thacker: I would obtain a family history. Using a population-based risk assessment such as the Gail model, I would calculate her absolute risk of breast cancer based on her duration of EPT use. I might offer her a lower-dose regimen. A conjugated equine estrogen dosage of 0.3 mg/day may be as effective in a 67-year-old woman as 0.625 mg/day is in a younger woman in terms of relieving vasomotor symptoms, depending on individual metabolism. We do have evidence from the HOPE trial that 0.3 mg/day is effective for relief of vasomotor symptoms.1 In addition, data from the Nurses’ Health Study show no increased risk of stroke with 0.3 mg/day, as opposed to the increased risk with 0.625 mg/day, and there are other data showing that the risk of stroke is possibly related to dosage.2
At the same time, we do not yet have long-term data to show that the lower dose is necessarily safer and we do not have data on bone fracture risk with the lower dose, so I would want to know this patient’s bone mineral density (BMD). I would also want to know about her cardiovascular risk profile, including her lipid profile, and I would want more details about her sexual function.
Dr. McKenzie: I will supply a few more case details. This patient’s body mass index (BMI) was 24 kg/m2. She exercised regularly. Her BMD was normal for her age. She was taking a statin to treat hyperlipidemia. She was a nonsmoker, and her family history was unremarkable. Does any of this information change the way that you would counsel her?
Dr. Howard Hodis: Knowing her BMI and that she was on a statin, I would have even less of a problem reinitiating HT.
Dr. McKenzie: Well, EPT was reinitiated in this patient at a lower dose (0.45/1.5 mg), and she was satisfied. At her most recent visit, several years later, the possibility of reducing her dose of HT was offered; however, the patient is happy with her quality of life and accepts whatever risk that continued HT may bring. She inquired about transdermal testosterone to restore her sex drive, and it was agreed that if it receives US marketing approval for women with decreased libido, a 24-week trial would be attempted.
Dr. Hodis: If you look at the data, this patient not only may enhance her quality of life by continuing HT but might extend it as well.
Dr. Thacker: Many patients inquire about using testosterone only, without estrogen, for treating dyspareunia and low libido. Clinicians must understand that testosterone is aromatized to estrogen. If a patient is on a high dose of oral estrogen, I would consider switching to transdermal estrogen before trying testosterone, whose use in women remains off-label in the United States. But the patient in our case has been doing well for several years on low-dose estrogen and she still has her ovaries.
Dr. Margery Gass: Some colleagues and I completed a study, which was presented at a recent Endocrine Society meeting,3 in which transdermal testosterone was just as effective without estrogen in increasing libido. But this remains moot for general clinical practice unless the transdermal testosterone patch is approved in this country (as it is already approved for use in women in Europe).
Dr. Hodis: Would any of you be worried about this patient’s fracture risk after having HT stopped following 15 years of use? Data show that the rate of bone loss after abrupt cessation of HT is just as great as when a woman is going through menopause.
Dr. Gass: Yes, and that is exactly the point. The woman should be assessed under these circumstances just as she would be at menopause, using the same risk factors.
Dr. Thacker: I think that underscores that there is risk in stopping treatment, just as there is in taking treatment or not taking treatment, and all of these risks should be considered. Many times, once a patient is off HT, some clinicians forget to check the patient’s BMD or to do a complete genital examination.
Dr. Sikon: Many providers who do not specialize in women’s health may forget that when HT is stopped, it is as if a newly menopausal state is being created. Providers need to think about ensuing changes in bone and genitourinary status as well as quality-of-life concerns.
Dr. McKenzie: In today’s clinical environment, there is awareness of the importance of long-term bone health because patients are living longer. The use of BMD measurements in practice is clearly expanding.
Dr. Thacker: It is worth noting that all of the drugs used to treat osteoporosis have been studied primarily in women who already have osteoporosis. The therapy with the most data to support a reduction in the risk of all types of fracture is HT. These data are very impressive, and although fracture prevention would not be the sole reason for using HT, it can make the overall risk-benefit assessment easier, particularly if it can be determined whether or not an individual patient is at high risk of venous thromboembolism (VTE).