Michelle P. Warren, MD Columbia University Medical Center, New York, New York mpw1@columbia.edu
Dr Warren serves as a consultant on advisory boards to Depomed, Pfizer, QuatRx, Wolters Kluwer, and Yoplait; is on the speakers bureau of Upsher Smith and Amgen; and has received research support from Ferring, Pfizer, and Wyeth.
Editorial support for this manuscript was provided by Bo Choi, PhD, and funded by Wyeth, which was acquired by Pfizer in October 2009. The author was not compensated and retained full editorial control over the content of the manuscript.
The Journal of Family Practice no longer accepts articles whose authors have received writing assistance from commercially sponsored third parties. This article was accepted prior to implementation of this policy.
A newly published WHI follow-up study has yielded similar findings regarding the incidence of invasive breast cancer with EPT. The small increase in cancer incidence compared with placebo was associated with positive nodes and the death rate in this group was also higher (2.6 deaths vs 1.3 per 10,000 women). These findings do not apply to ET alone.50
Breast cancer risk in perspective. When interpreting increased risk, consider the absolute risk. In the WHI study, the absolute risk of invasive breast cancer increased by 4 to 6 cases per 10,000 women per year in the EPT group vs placebo.47 Similarly, a systematic review of clinical studies showed that EPT was associated with an increase of 4 breast cancer cases per 10,000 women per year.51 The increased risk of breast cancer with combined EPT is similar to that associated with early menarche or late menopause and is smaller than that associated with nulliparity or having children after 30 years of age.52
Assessing risks and benefits for the potential HT patient
The first step in treating patients who have hot flashes is to determine the extent of their symptoms and the effect on their quality of life (TABLE).5,10,23 Two hot flashes a day is considered mild and will usually respond to lifestyle measures such as exercising, avoiding alcohol and spicy foods, and staying in a cool environment. If the patient wakes in the night with hot flashes and night sweats that lead to insomnia, this may be more serious and require treatment. Consider HT for moderate-to-severe hot flashes—ie, 5 to 7 a day. HT is the only pharmacologic therapy indicated for the treatment of hot flashes.
Although professional guidelines recommend appropriate use of HT, publication of the WHI study caused many patients to mistrust and fear hormonal approaches to managing menopausal symptoms.3,4,53 Among those who discontinued HT, many have had vasomotor symptoms recur, and some patients remain untreated.53 A thorough discussion of individual needs and risk factors can help assess whether a patient is a suitable candidate for HT, and patient education and counseling may help alleviate concerns.54
When considering HT for a patient, take into account risk factors, such as baseline disease, age at menopause, cause of menopause, prior hormone use, variations in HT used, and age and time elapsed since menopause.5 An individual’s risks for cardiovascular disease, breast cancer, and osteoporotic fractures will help determine the most appropriate treatment.55 In the WHI, symptomatic women who were younger and closer to the menopausal transition experienced the greatest relief of vasomotor symptoms with EPT and were less likely to experience adverse effects compared with older women.56 The WHI data also showed that the prevalence of menopausal symptoms decreased with increasing age, occurring most commonly in women ages 50 to 54 years.56 The WHI findings have been shown to apply to HT regimens in general.57
Specific recommendations. Current prescribing guidelines5 recommend using ET/EPT to treat moderate-to-severe vasomotor symptoms associated with menopause when the benefits of short-term therapy outweigh the risks. For women who experience mainly vaginal symptoms rather than vasomotor symptoms, vaginal ET is recommended.
FAST TRACK
Hormone therapy is not recommended for coronary protection in women of any age.
HT is not recommended for coronary protection in women of any age, as there is evidence that use in older women increases the risk of cardiovascular events.5 However, HT does not appear to increase the risk of CV events if initiated by women ages 50 to 59 years or by those within 10 years of menopause. There is evidence of an increased risk of VTE with oral HT, although absolute risk is low in women ages 50 to 59 years.5
To prevent further bone loss and reduce the risk of osteoporotic fracture in women with established reduction in bone mass, the guidelines recommend extended use of HT, regardless of menopausal symptoms, when alternate therapies are not appropriate or cause side effects or when the safety and hazards of extended use of alternate therapies are not well established.5
Breast cancer risk increases with EPT use beyond 3 to 5 years, although the absolute risk is still considered rare.5 Clinical evidence, including findings from the WHI study16 and the Women’s Health Study,43 shows no increase in the risk of breast cancer in women receiving ET. Further, the risk of breast cancer with ET may be lower in certain subgroups of women, such as those with lower Gail risk estimates based on age, history of benign breast disease, age of menarche, age of first birth, race/ ethnicity, and mothers and sisters with breast cancer;58 women with no first-degree relatives with breast cancer; women without benign breast disease; and women with no prior hormone use.45
