Hormone replacement therapy: The right choice for your patient?

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Case Reports

Hormone replacement therapy: The right choice for your patient?

J Fam Pract. 2005 May;54(5):428-436

By

Shou Ling Leong, MD

Deborah R. Erickson, MD

Richard C. Pees, MD

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References

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2. Anderson GL, Limacher M, Assaf AR, et al. Women’s Health Initiative Steering Committee Effects of conjugated equine estrogen in postmenopausal women with hysterectomy, the women’s health initiative randomized control trial. The Women’s Health Initiative Steering Committee. JAMA 2004;291:1701-1712.

3. The Hormone Therapy Advisory Panel of the North American Menopause Society position statement on hormone therapy. Available at: www.menopause.org. Accessed on April 1, 2005

4. Loprinzi CL, Kugler JW, Sloan JA, et al. Venlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial. Lancet 2000;356:2059-2063.

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6. Nagamani M, Kelver ME, Smith ER. Treatment of menopausal hot flashes with transdermal administration of clonidine. Am J Obstet Gynecol 1987;156:561-565.

7. Upmalis DH, Lobo R, Bradley L, Warren M, Cone FL, Lamia CA. Vasomotor symptom relief by soy isoflavone extract tablets in postmenopausal women: a multicenter, double-blind, randomized, placebo-controlled study. Menopause 2000;7:236-242.

8. Tice JA, Ettinger B, Ensrud K, Wallace R, Blackwell T, Cummings SR. Phytoestrogen supplements for the treatment of hot flashes: the isoflavone clover extract (ICE) study: a randomized controlled trial. JAMA 2003;290:207-214.

9. Kronenberg F, Fugh-Berman A. Complementary and alternative medicine for menopausal symptoms: a review of randomized, controlled trials. Ann Intern Med 2002;137:805-813.

10. Simunic V, Banovic I, Ciglar S, Jeren L, Pavicic Baldani D, Sprem M. Local estrogen treatment in patients with urogenital symptoms. Int J Gynecol Obstet 2003;82:187-197.

11. Fantl JA, Newman DK, Colling J, et al. Urinary Incontinence in Adults: Acute and Chronic Management. Clinical Practice Guideline, No. 2; 1996 update. AHCPR Publication No. 96-0682. Rockville, Md: US Department of Health and Human Services, Public Health Services, Agency for Health Care Policy and Research 1996.

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13. Millard RJ, Moore K, Rencken R, Yalcin I, Bump RC. Duloxetine UI Study Group Duloxetine vs. placebo in the treatment of stress urinary incontinence: a four-continent randomized clinical trial. BJU International 2004;93:311-318.

14. Dmochowski RR, Miklos JR, Norton PA, Zinner NR, Yalcin I, Bump RC. Duloxetine UI Study Group: Duloxetine versus placebo for the treatment of North American women with stress urinary incontinence J Urol 2003;170:1259-1263.

15. Leach GE, Dmochowski RR, Appell RA, et al. Female stress urinary incontinence clinical guidelines panel summary report on surgical management of female stress urinary incontinence. J Urol 1997;158:875-880.

16. Burgio KL, Pearce KL, Lucco AJ. Staying Dry: A Practical Guide to Bladder Control. Baltimore, Md: Johns Hopkins University Press; 1989.

17. Hay-Smith J, Herbison P, Ellis G, Moore K. Anticholinergic drugs versus placebo for overactive bladder syndrome in adults. Cochrane Database Syst Rev 2002;(3) CD003781.-

18. Halaska M, Ralph G, Weidemann A, et al. Controlled, double-blind, multicentre clinical trial to investigate long-term tolerability and efficacy of trospium chloride in patients with detrusor instability. World J Urol 2003;29:392-399.

19. Gordon D, Groutz A, Ascher-Landsberg J, Lessing JB, David MP, Razz O. Double-blind, placebo-controlled study of magnesium hydroxide for treatment of sensory urgency and detrusor instability: preliminary results. Br J Obstet Gynaecol 1998;105:667-669.

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Drug brand names

Calcitonin • Calcimar, Cibacalcin, Miacalcin
Cephalexin • Biocef, Keflex, Keftab
Clonidine • Catapres
Duloxetine • Cymbalta
Fluoxetine • Prozac
Gabapentin • Neurontin
Megestrol acetate • Megace
Nitrofurantoin • Furadantin, Macrobid, Macrodantin
Oxybutynin • Ditropan, Oxytrol
Paroxetine • Paxil
Raloxifene • Evista
Tolterodine • Detrol
Trospium chloride • Sanctura
Venlafaxine • Effexor

CORRESPONDING AUTHOR Shou Ling Leong, MD, Penn State College of Medicine, Penn State Milton S. Hershey Medical Center, P.O. Box 850, Hershey, PA 17033 -0850. E-mail: sleong@psu.edu

Mrs JC, a 55-year-old woman, arrives for her annual gynecologic exam. Besides wanting to update her Pap smear and mammogram, she would like to discuss estrogen replacement. She reached menopause at age 52 and began taking estrogen for hot flashes and night sweats. Her cholesterol levels have been elevated since menopause. She read that estrogen can lower cholesterol levels and therefore may possibly reduce her risk for heart disease.

She did very well with estrogen. Her hot flashes and night sweats disappeared and she felt great. However, after hearing news reports about the danger of estrogen, she discontinued the hormone pills a few months ago. She is now feeling poorly with hot flashes, night sweats, vaginal dryness, and occasional stress incontinence. She has many questions and concerns and eagerly seeks your advice about what to do.

Medical history

Borderline hypertension
Hyperlipidemia
Obesity: body-mass index of 32

Family history

Mother, age 75, has hyperlipidemia, hypertension, myocardial infarction (MI) at age 60, and osteoporosis
Father, died at age 55 of MI; had hypertension and diabetes
Her grandparents also had history of stroke and heart disease, but she doesn’t know all the details about their health. She believes her maternal grandmother broke her hip when she was elderly.

Social history

Married, 2 children, works as an attorney with the local government. Her job is fairly demanding
Does not smoke, occasional alcohol consumption
Does not exercise on a regular basis

Review of systems

Negative except for hot flashes, night sweats, vaginal dryness, and occasional stress incontinence.

Physical examination

Alert female in no distress. Blood pressure, 145/90 mm Hg; weight, 165 lbs; pulse, 82; respiration, 18; temperature, 98.1°F
HEENT exam, normal
Neck, heart, lung, abdomen, breast, and pelvic exams are all normal except for mild atrophic changes of the vaginal and genital tracts.

You perform the gynecologic exam and order a mammogram. Mrs JC has not been seen for 2 years. Her lipid profile done 2 years ago was elevated, but Mrs JC did not repeat the tests as requested. You explain that you would like to further define her risk factors and would like to order a few tests. Making a well-informed decision on hormone replacement therapy (HRT) is complex and requires more information and adequate time for a full discussion. You would like to see her after her laboratory tests and will reserve time to address her concerns and questions.

Laboratory tests

Complete blood count, normal

Cholesterol, 250 mg/dL (LDL, 130 mg/dL; HDL, 45 mg/dL)

Triglyceride, 220 mg/dL

Electrolytes, blood urea nitrogen/creatine (BUN/Cr) ratio, normal; glucose, 85 mg/dL

Mrs JC has many symptoms of menopause:

Vasomotor instability
Urogenital symptoms She also has risk factors:
Cardiac: hypertension, hyperlipidemia, obesity
Osteoporosis: family history, sedentary lifestyle

Before addressing Mrs JC’s specific concerns, you review the findings of the Women’s Health Initiative (WHI) study,^1,2 which probably prompted her concerns. You also have been asked to lead an upcoming geriatric grand round presentation on HRT, and you further prepare for both encounters by meeting with colleagues Dr Richard Pees, a gynecologist, and Dr Deborah Erickson, a urologist, to discuss practical applications of the WHI findings.

Findings of the WHI

WHI, sponsored by the National Institute of Health, comprised 2 multicentered clinical trials to determine if conjugated equine estrogen (CEE) given alone for women who had a hysterectomy or in combination with progestin (MPA, medroxyprogesterone acetate) would reduce the risk of cardiovascular events. The study also assessed the long-term risks and benefits of postmenopausal hormone therapy in other chronic disease prevention.

Exclusion criteria for the study included competing risks with survival <3 years, prior breast cancer, low hematocrit or platelets, severe menopausal symptoms, alcoholism, mental illness, and dementia. In this study, 27,000 women aged 50 to 79 years (mean age, 63) were randomized to take hormone or placebo.

The combined CEE/MPA (Prempro) trial, with 16,000 women enrolled, was discontinued at 5.2 years, on July 2002. The unopposed CEE (Premarin) trial, with 11,000 women, was discontinued at 6.8 years, on February 2004. The study was stopped earlier than planned (2005) because of increased adverse events in the group taking hormone.

FAST TRACK

The estrogen-progestin arm of the WHI had more cases of coronary heart disease, breast cancer, stroke, and venous thromboembolism

TABLE 1 summarizes the absolute risks—number of events per 10,000 as compared with the control group—for both arms of the study. In the CEE/MPA arm, there were more cases per 10,000 of coronary heart disease (+7), breast cancer (+8), stroke (+8), and venous thromboembolic disease (VTE) including deep vein thrombosis/pulmonary embolism (DVT/PE) (+18). However, there were fewer cases per 10,000 of colorectal cancer (–6) and hip fracture (–5).