Anything Goes: Discontinuation of Hormone Therapy

Case Report

A 56-year-old woman has been on continuous combined hormone therapy (HT) since menopause occurred at age 51. She chose to take HT because she had experienced significant vasomotor symptoms. These symptoms all resolved with the use of transdermal estradiol and oral micronized progesterone taken in a continuous combined manner. She has had no side effects from the HT and has done well. The patient is aware of the findings of the Estrogen and Progestin arm (E + P) arm of the Women's Health Initiative (WHI) and is concerned about long-term use of HT and the risk of breast cancer. She has decided to discontinue all HT at this time and is asking you to recommend the best way to discontinue the therapy.

Based on current evidence, you recommend:

A. Abrupt discontinuation of HT

Discussion

Publication of the E + P arm of the WHI in 2002 heralded a new era in the use of HT for treatment of menopausal symptoms. ¹ Concerns related to the initial findings of increased risk of coronary heart disease (CHD), invasive breast cancer, and stroke prompted a brisk and significant response from physicians and patients in the United States. In the months after publication of the initial results, many women discontinued HT. In the year after the results were made available to the public, prescriptions in the United States for conjugated equine estrogen and medroxyprogesterone acetate (CEE + MPA) declined by 66%, and those for (CEE declined) by 33% ² .

Hot flashes are experienced by 60%–90% of perimenopausal women, ³ and estrogen is the most effective therapy for controlling hot flashes, with an estimated decrease in frequency of hot flashes of 75% (95% confidence interval [CI] 64%–82%) and a reduction in severity. ⁴ With cessation of HT, hot flashes usually recur within 4–6 days of stopping most hormone preparations; however, CEE may demonstrate a more prolonged effect on hot flash control as a result of storage in adipose tissue. ⁵

The Food and Drug Administration (FDA) suggests using HT in the smallest effective dose for the shortest duration. The lowest effective dose of estrogen can be determined by using the desired reduction in hot flash frequency and severity as a clinical end point of therapy. Because there is no clear definition of a short duration, findings from the WHI often are used to guide duration, as the study demonstrated increased risk of breast cancer after 3–5 years of combined E + P therapy. Many clinicians and patients consider stopping HT at this point. ¹

Clinicians engaged in the care of perimenopausal and menopausal women are often asked to recommend the optimal method of stopping HT. Unfortunately, current data are limited in providing evidence-based guidelines. The North American Menopause Society does not recommend a specific approach to discontinuance. ⁶ In one randomized clinical trial of 91 women, the investigators had one group of women stop hormones abruptly and the second group taper one pill per week (presumably a combined pill of E + P) such that they stopped HT completely after 6 months. At the end of 1 year, the rates and severity of vasomotor symptom recurrence were similar in both groups. ⁷

The paucity of data to guide decision making creates an opportunity to engage in collaborative decision making with each patient. Risks and benefits of ongoing HT need to be considered in the context of the individual patient's symptoms, expectations, and personal values. Further, before stopping hormonal preparations, it is helpful to review available nonhormonal strategies for treating hot flashes. Although less effective than estrogen, selected antidepressants (paroxetine, venlafaxine, fluoxetine, and sertraline) and gabapentin may be reasonable options in select groups of women. ⁸

Various complementary therapies, such as soy, red clover, flaxseed, black cohosh, and vitamin E, have been studied in randomized placebo-controlled trials. Soy has shown modest efficacy at a dose of 50 mg/day in some studies. ⁹ Black cohosh studies have shown conflicting results, and other therapies have not been found to be effective. Herbal therapies, including evening primrose oil, dong quai, and wild yam, also have not been shown to improve menopausal symptoms when compared to placebo. Although investigations into mind-body and behavior therapies (yoga, relaxation training, hypnosis, and paced respiration) are becoming increasingly popular and sought out by women, large randomized controlled trials are lacking and future research is needed to evaluate their efficacy. ¹⁰

Practical considerations also should play a role in guiding therapy. Hot flashes are often aggravated by warmer temperatures and stress. Consideration could be given to stopping HT during the cooler months of the year or when the patient predicts her calendar will be free of conflict.

Because estrogen is primarily responsible for symptom control of hot flashes, one strategy to consider is to taper the dose or lengthen the dosing interval of the estrogen. This method of tapering allows the patient to observe her symptom relief on lower doses of estrogen and, thus, to determine the lowest effective dose should she decide to resume therapy.

Answer: D. Evidence does not support one method of discontinuation over another