Hormone Replacement Therapy Most Benefits Women Under 60

Menopause starts 12 months after the last menstrual period or when menstruation has stopped because of a clinical reason, such as removal of the ovaries, and symptoms may include hot flashes, sleep disturbances, urinary problems, and vaginal dryness.¹

In 2017, the North American Menopause Society updated its 2012 Hormone Therapy Position Statement based on new evidence of the benefits versus risks.² The 2017 position statement discussed that hormone replacement therapy (HRT) provides the most benefit for women younger than 60 years within 10 years of menopause onset and no treatment contraindications.² This patient population can be treated for vasomotor symptoms, such as hot flashes. However, the risks of HRT may outweigh the benefits for women 60 years and older or those more than 10 or 20 years from menopause onset.² These patients may have a greater risk of coronary heart disease, dementia, stroke, and venous thromboembolism.² Pharmacists can play an important role in educating patients about HRT, as well as recommending pharmacotherapy based on age and medical history.

COUNSELING PEARLS, TREATMENT OPTIONS

Unopposed estrogen should only be given to women who have had a hysterectomy.² Combined estrogen-progestin therapy is recommended for women with an intact uterus to prevent endometrial cancer.² Patients should use HRT for the shortest duration possible at the lowest dose for symptom management.² Evidence suggests that the risk of breast cancer with HRT may depend on dose, duration of use, and regimen.² Systemic HRT is not recommended in breast cancer survivors, as there is an increased risk of recurrence.²

There are various HRT options, which include systemic and vaginal estrogen treatments. Estrogen-only medications include a variety of dosage forms, such as gels, injections, oral, patches, vaginal creams and rings (figure^2,3). Examples include estradiol (Alora), estradiol (Climara), estradiol (Divigel), and estradiol acetate (Femring).³ Common adverse effects may include breast tenderness, fluid retention, hair loss, headaches, and nausea. The genitourinary syndrome of menopause, which includes vaginal burning, dryness, and irritation, may be treated with low-dose topical vaginal estrogens, which are generally considered safe, as there is little systemic absorption.² Progestin therapy is not needed with low-dose vaginal estrogen, but there is a lack of randomized trial information available beyond 1 year.²

Combination estrogen-progestin medications include oral and patch dosage forms, such as estradiol/drospirenone (Angeliq), estradiol/levonorgestrel (Climara Pro), and estradiol/norethindrone acetate (Activella).³ Common adverse effects include bloating, breast tenderness, fluid retention, hair loss, headaches, nausea, and vomiting. Conjugated estrogens/bazedoxifene (Duavee) is a combination estrogen-hormone medication.³ Bazedoxifene is an estrogen agonist/antagonist, also known as a selective estrogen receptor modulator, which can protect against endometrial hyperplasia without the need for progestin.2 Bazedoxifene therapy may result in an increased risk of venous thromboembolism like estrogen does, so it is important to counsel patients about the signs and symptoms of blood clots.³

The North American Menopause Society recommends avoiding the use of compounded bioidentical hormones, because of the risk of overdosing or underdosing and a lack of efficacy and safety studies.² Also, salivary hormone testing to determine the dose is unreliable, because of differences in hormone pharmacokinetics and absorption.² The FDA does not have evidence that compounded bioidentical hormones are safe and effective.⁴

Pharmacists should educate patients about the risks of using compounded bioidentical hormones. FDA-approved bioidentical HRT, including estradiol and estrone, is monitored and regulated for safety and efficacy.²

HRT AND DEMENTIA

There has been mixed evidence as to whether HRT has a protective effect or increases the risk of dementia. One observational study found an increased risk of Alzheimer disease in patients taking systemic HRT.⁵ The results of a 12-year population-based study showed that longer HRT use, especially in older women, was associated with higher cognitive status later in life.⁶ Also, individuals initiating HRT within 5 years of menopause had higher cognitive scores than those starting HRT 6 or more years later.⁶ There is ongoing research known as the Kronos Early Estrogen Prevention Study that is evaluating the effects of HRT and normal aging on cognitive performance, imaging markers of Alzheimer disease, and brain structure in women who participated in the original Kronos Early Estrogen Prevention Study trial.⁷ This is a follow-up study evaluating these women 13 years after enrollment. Additionally, the study participants were randomized to receive oral or transdermal estrogen treatments or a placebo within 3 years of menopause.7 Because this study is more robust, it may shed more light on the effect of HRT on dementia.

Jennifer Gershman, PharmD, CPh, is a drug information pharmacist and Pharmacy Times® contributor who resides in South Florida.

REFERENCES

• Menopause. Mayo Clinic. Updated August 7, 2017. Accessed May 28, 2020. https://wwwmayoclinic.org/diseases-conditions/menopause/diagnosis-treatment/drc- 20353401
• The NAMS 2017 Hormone Therapy Position Statement Advisory Panel. The 2017 hormone therapy position statement of The North American Menopause Society. Menopause. 2017;24(7):728-753. doi: 10.1097/GME.0000000000000921
• Menopause: medicines to help you. US Food & Drug Administration. Updated August 22, 2019. Accessed May 28, 2020. https://www.fda.gov/consumers/free-publications- women/menopause-medicines-help-you
• Menopause & hormones common questions. United States Food & Drug Administration. Accessed May 28, 2020. https://www.fda.gov/media/130242/download
• Savolainen-Peltonen H, Rahkola-Soisalo P, Hoti F, et al. Use of postmenopausal hormone therapy and risk of Alzheimer’s disease in Finland: nationwide case-control study. BMJ. 2019;364:l665. doi: 10.1136/bmj.l665
• Matyi JM, Rattinger GB, Schwartz S, Buhusi M, Tschanz JT. Lifetime estrogen exposure and cognition in late life: the Cache County Study. Menopause. 2019; 26(12):1366-1374. doi: 10.1097/GME.0000000000001405
• The Kronos Early Estrogen Prevention Study (KEEPS). National Institutes of Health. Updated August 21, 2019. Accessed May 27, 2020. ClinicalTrials.gov. https:// www.clinicaltrials.gov/ct2/show/NCT03718494