The 2017 Hormone Therapy Position Statement of The North American Menopause Society

The North American Menopause Society 2017 Hormone Therapy Position Statement Advisory Panel

Disclosures

The North American Menopause Society (NAMS). 2018;24(7):728-753. 

In This Article

Therapeutic Issues: Extended Use and Risks of Discontinuation

Extended use of HT may benefit women for relief of persistent VMS, prevention of bone loss and fracture, or prevention or treatment of GSM. Vasomotor symptoms have an approximately 50% chance of recurring when HT is discontinued, independent of age and duration of use.[57,58] Bone loss and fracture risk continue to progress throughout aging, as does untreated GSM. With discontinuation of HT, virtually all women will lose BMD, with increased risk of bone fractures[128,263] and excess mortality from hip fracture,[264] although no rebound in fractures was seen in WHI off-treatment,[129] and GSM will recur.

Concern regarding HT use centers around potential risk on the breast or CV system with initiation of HT at an age older than 60 years or more than 10 or 20 years from menopause onset and with increased duration of therapy.

In the WHI, many but not all benefits and risks did not persist beyond 5 to 7 years after therapy was stopped.[265] An elevated risk (rare absolute risk) of breast cancer persisted (HR, 1.28; 95% CI, 1.11–1.48) with CEE + MPA during a median 13-year cumulative follow-up (5.6 y of treatment plus 8.2 y of postintervention observation), but most CVD risk became neutral (Figure 1).[14] During the cumulative follow-up overall, a significant reduction in hip fracture risk persisted (HR, 0.81; 95% CI, 0.68–0.97), and a reduction in endometrial cancer risk was found (HR, 0.67; 95% CI, 0.49–0.91). For women randomized to CEE alone, the reduction in breast cancer risk became significant (HR, 0.79; 95% CI, 0.65–0.97) during the median 13-year cumulative follow-up (7.2 y of treatment plus 6.6 y of postintervention observation).[14,265]

All-cause mortality was neutral after a median 13-year cumulative follow-up for CEE + MPA in the WHI (HR, 1.01; 95% CI, 0.91–1.11) and not significantly reduced in the 50- to 59-year age group when examined separately nor for CEE alone (Figure 1).[14] Similarly, CV mortality was neutral poststopping in all age groups. Finnish population observational studies, using an age-matched standardized Finnish population as controls, suggest that CV mortality, CHD, and stroke mortality may increase in the year after discontinuing HT, but reduced risk was seen during follow-up the next year.[266] Within the first posttreatment year, the risk of cardiac death was significantly elevated (standardized mortality ratio [SMR], 1.26; 95% CI; 1.16–1.37), whereas follow-up for longer than 1 year was accompanied with a reduction (SMR, 0.75; 95% CI, 0.72–0.78). The risk of stroke death in the first posttreatment year was increased (SMR, 1.63; 95% CI, 1.47–1.79), but follow-up for longer than 1 year was accompanied with a reduced risk (SMR, 0.89; 95% CI, 0.85–0.94). This data has not been seen in RCTs and needs validation.

Key Points

• Decisions about duration of use remain challenging because long-term follow-up data are complicated, especi ally in regard to breast cancer.

   - Benefits include relief of persistent VMS, prevention of bone loss and fracture, and prevention or treatment of GSM.

   - Concerns include potential risk of breast cancer that may increase with longer duration of use.

   - Coronary heart disease and all-cause mortality may be decreased when HT is initiated closer to menopause onset, with fewer MIs with estrogen alone. However, women who initiate HT when aged older than 60 years or who are more than 10 years, or clearly by 20 years, from menopause onset are at higher absolute risks of CHD, VTE, and stroke than women initiating HT in early menopause.[177]

• Research is needed on benefits and risks of longer durations of use and potential benefits and risks with discontinuation.

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