Cases in Menopause
Your postmenopausal patient reports a history of migraine
Would a trial of hormone therapy increase her risk of stroke?
Data on the risk of osteoporotic fractures among women using the ultra-low-dose estradiol patch are not available.
Use of HT to prevent osteoporosis is appropriate for women who have other indications for HT, such as VMS. For women using HT who no longer experience VMS, long-term use of HT for osteoporosis is controversial. However, it may be considered for women at elevated risk for osteoporosis when skeleton-specific treatments (eg, bisphosphonates) are not tolerated or when such women prefer not to use skeleton-specific therapy.
FDA package labeling for systemic HT indicates that, “When prescribing solely for the prevention of postmenopausal osteoporosis, therapy only should be considered for women at significant risk of osteoporosis, and non-estrogen medications should be carefully considered.”14
The NAMS 2012 Position Statement on HT states: “Provided that the woman is well aware of the potential benefits and risks and has clinical supervision, extending [estrogen-progestin therapy] use with the lowest effective dose is acceptable under some circumstances, including 1) for the woman who has determined that the benefits of menopause symptom relief outweigh risks, notably after failing an attempt to stop [estrogen-progestin therapy], and 2) for the woman at high risk of fracture for whom alternate therapies are not appropriate or cause unacceptable adverse effects.”2
A 2014 Practice Bulletin from the American College of Obstetricians and Gynecologists (ACOG) on the management of menopausal symptoms states: “The decision to continue HT should be individualized and be based on a woman’s symptoms and the risk–benefit ratio, regardless of age. Because some women aged 65 years and older may continue to need systemic HT for the management of vasomotor symptoms, ACOG recommends against routine discontinuation of systemic estrogen at age 65. As with younger women, use of HT and estrogen therapy should be individualized based on each woman’s risk–benefit ratio and clinical presentation.”15
As I have detailed, doses of HT that are lower than those used to treat VMS can prevent loss of BMD. Accordingly, clinicians prescribing HT for the sole indication of osteoporosis prevention should use doses lower than those for standard HT. Moreover, clinicians prescribing HT specifically to prevent osteoporosis should recognize the elevated risk of breast cancer with estrogen-progestin therapy. Extended use of estrogen-only therapy is more appropriate for this indication.
Related Article: Your menopausal patient's breast biopsy reveals atypical hyperplasia JoAnn V. Pinkerton, MD (Cases in Menopause, May 2013)
While estrogen-only therapy is common in women following hysterectomy, ultra-low-dose estrogen therapy with regular endometrial monitoring also can be considered in women with an intact uterus.
Also be aware that BMD declines rapidly after discontinuation of HT (in contrast with bisphosphonates), so alternative agents to maintain BMD should be considered when HT is stopped.16
HOW SAFE IS EXTENDED USE OF SYSTEMIC HT?
The incidence of breast cancer and mortality from breast cancer increase after 3 to 5 years of estrogen-progestin therapy, and the risk of stroke remains elevated throughout use of combination as well as estrogen-only HT.2 Women with an intact uterus who choose to extend the duration of combination therapy beyond 5 years for control of VMS or protection against osteoporosis, or both, need to be candidly counseled about these concerns. No increase in the risk of breast cancer was observed in the estrogen-only arm of the WHI randomized, clinical trial (mean duration of CEE therapy of 7.1 years).17
Related Article: Stop enforcing a 5-year rule for menopausal hormone therapy Robert L. Reid, MD (Stop/Start, December 2013)
Long-term risks of oral estrogen
Among women who initiate HT at the time of menopause, long-term use does not appear to increase the risk of coronary heart disease (CHD), although follow-up in clinical trials has not extended beyond 7 years for estrogen-progestin therapy, and midlife may bring increases in a woman’s baseline cardiovascular risk.2 However, in the WHI, women who initiated oral estrogen-only or estrogen-progestin therapy later in menopause experienced an increased risk of CHD,18 underscoring the need for caution and individualization in this patient population.
Oral HT increases the risk of venous thromboembolism (VTE) and stroke.2 In addition, age is an independent risk factor for these two outcomes. Observational studies suggest that, in contrast with oral estrogen, transdermal HT does not increase the risk of VTE.19–24 Randomized trial data are lacking.
