Cases in Menopause

Your menopausal patient’s breast biopsy reveals atypical hyperplasia

OBG Manag. 2013 May;25(5):36-41

How do you now manage her menopausal symptoms, including bothersome hot flashes?

References

1. North American Menopause Society. Treatment of menopause-associated vasomotor symptoms: position statement of The North American Menopause Society. Menopause. 2004;11(1):11-33.

2. Pinkerton JV, Stovall DW, Kightlinger RS. Advances in the treatment of menopausal symptoms. Womens Health (Lond Engl). 2009;5(4):361-384.

3. Ghaleiha A, Jahangard L, Sherafat Z, et al. Oxybutynin reduces sweating in depressed patients treated with sertraline: a double-blink, placebo-controlled, clinical study. Neuropsychiatr Dis Treat. 2012;8:407-412.

4. Hall E, Frey BN, Soares CN. Non-hormonal treatment strategies for vasomotor symptoms: a critical review. Drugs. 2011;71(3):287-304.

5. Pinkerton JV, Archer DF, Guico-Pabia CJ, Hwang E, Cheng RF. Maintenance of the efficacy of desvenlafaxine in menopausal vasomotor symptoms: a 1-year randomized controlled trial. Menopause. 2013;20(1):38-46.

6. Simon JA, Sanacora G, Bhaskar S, Lippman J. Safety and efficacy of low-dose mesylate salt of paroxetine (LDMP) for the treatment of vasomotor symptoms (VMS) associated with menopause: a 24-week randomized, placebo-controlled phase 3 study. Menopause. 2012;19(12):1371.-

7. Freeman EW, Guthrie KA, Caan B, et al. Efficacy of escitalopram for hot flashes in healthy menopausal women: a randomized controlled trial. JAMA. 2011;305(3):267-274.

8. Pinkerton JV, Kagan R, Portman D, Sathyanarayan RK, Sweeney M. Efficacy of gabapentin extended release in the treatment of menopausal hot flashes: results of the Breeze 3 study. Menopause. 2012;19(12):1377.-

9. MacBride MB, Rhodes DJ, Shuster LT. Vulvovaginal atrophy. Mayo Clin Proc. 2010;85(1):87-94.

10. Bedell S, Nachtigall M, Naftolin F. The pros and cons of plant estrogens for menopause [published online ahead of print December 25 2012]. J Steroid Biochem Mol Biol. 2012. doi: 10.1016/j.jsbmb.2012.12.004.

11. Moegele M, Buchholz S, Seitz S, Ortmann O. Vaginal estrogen therapy in postmenopausal breast cancer patients treated with aromatase inhibitors. Arch Gynecol Obstet. 2012;285(5):1397-402.

12. North American Menopause Society. The role of local vaginal estrogen for treatment of vaginal atrophy in postmenopausal women: 2007 position statement of The North American Menopause Society. Menopause. 2007;14(3 Pt 1):355-371.

13. Archer DF. Efficacy and tolerability of local estrogen therapy for urogenital atrophy. Menopause. 2010;17(1):194-203.

14. Simon JA. Vulvovaginal atrophy: new and upcoming approaches. Menopause. 2009;16(1):5-7.

15. Kaunitz AM. Transdermal and vaginal estradiol for the treatment of menopausal symptoms: the nuts and bolts. Menopause. 2012;19(6):602-603.

16. Pruthi S, Simon JA, Early AP. Current overview of the management of urogenital atrophy in women with breast cancer. Breast J. 2011;17(4):403-408.

17. Menes TS, Kerlikowske K, Jaffer S, Seger D, Miglioretti D. Rates of atypical ductal hyperplasia declined with less use of postmenopausal hormone treatment: findings from the Breast Cancer Surveillance Consortium. Cancer Epidemiol Biomarkers Prev. 2009;18(11):2822-2828.

18. Santen RJ, Mansel R. Benign breast disorders. N Engl J Med. 2005;353(3):275-285.

19. Pinkerton JV, Shapiro M. The North American Menopause Society. Overview of available treatment options for VMS and VVA. Medscape Education Web site. http://www.medscape.org/viewarticle/763413. Published May 24 2012. Accessed February 23, 2013.

CASES IN MENOPAUSE

A new series brought to you by the menopause experts

	Andrew M. Kaunitz, MD Professor and Associate Chairman, Department of Obstetrics and Gynecology, University of Florida College of Medicine–Jacksonville. Dr. Kaunitz is a NAMS Board member and certified menopause practitioner. He also serves on the OBG Management Board of Editors.
	JoAnn V. Pinkerton, MD Professor, Department of Obstetrics and Gynecology, and Director, Division of Midlife Women’s Health, University of Virginia. Dr. Pinkerton is a North American Menopause Society (NAMS) past president and certified menopause practitioner. She also serves on the OBG Management Board of Editors.
	James A. Simon, MD Clinical Professor, Department of Obstetrics and Gynecology, George Washington University, and Medical Director, Women’s Health & Research Consultants, Washington, DC. Dr. Simon is a NAMS past president, a certified menopause practitioner, and a certified clinical densitometrist. He also serves on the OBG Management Board of Editors.

Disclosures
Dr. Kaunitz reports that his institution receives grant or research support from Agile, Bayer, Endoceutics, Teva, Medical Diagnostic Laboratories, and Noven, and that he is a consultant to Bayer, Merck, and Teva.

Dr. Pinkerton reports that her institution receives consulting fees from Pfizer, DepoMed, Shionogi, and Noven and multicenter research fees from DepoMed, Endoceutics, and Bionova.

Dr. Simon reports being a consultant to or on the advisory boards of Abbott Laboratories, Agile Therapeutics, Amgen, Ascend Therapeutics, BioSante, Depomed, Lelo, MD Therapeutics, Meda Pharmaceuticals, Merck, Noven, Novo Nordisk, Novogyne, Pfizer, Shionogi, Shippan Point Advisors LLC, Slate Pharmaceuticals, Sprout Pharmaceuticals, Teva, Warner Chilcott, and Watson. He also reports receiving (currently or in the past year) grant/research support from BioSante, EndoCeutics, Novo Nordisk, Novogyne, Palatin Technologies, Teva, and Warner Chilcott. He reports serving on the speakers bureaus of Amgen, Merck, Novartis, Noven, Novo Nordisk, Novogyne, Teva, and Warner Chilcott. Dr. Simon is currently the Chief Medical Officer for Sprout Pharmaceuticals.

CASE: Atypical ductal hyperplasia

Your 56-year-old, married, white patient has been on hormone therapy (HT) since age 52 for the treatment of vasomotor symptoms. She is taking a low-dose oral estrogen and micronized progesterone combination as she has an intact uterus. Her family history is positive for breast cancer, as her mother was diagnosed at age 68.

Her most recent annual screening mammogram shows linear calcifications. Because fine, linear, branching or casting calcifications are worrisome for atypical ductal hyperplasia (ADH) or ductal carcinoma in situ, a biopsy is recommended.

She elects to wean off and discontinue HT during the evaluation of her abnormal mammogram. The mammographic-guided stereotactic biopsy reveals ADH. She undergoes an open excisional biopsy, the results of which reveal extensive ADH with negative margins.

Six weeks after a lumpectomy she returns to your office reporting moderate to severe hot flashes that occur seven to 10 times per day and impair her sleep, leading to fatigue and “brain fog.” In addition, she is noticing vaginal dryness and dyspareunia despite use of lubricants. She requests treatment for her symptoms and wonders if she can restart HT systemically or vaginally.

How do you manage her hot flashes?

What are the alternatives to HT for hot flashes?

Certain lifestyle changes have been reported to provide relief for hot flushes.¹ These include:

use of layered clothing
maintenance of cool ambient temperature (particularly during sleep)
consumption of cool foods or beverages
relaxation techniques (such as deep breathing, or paced respirations, for 20 min three times per day).

Despite sparse data, avoiding triggers such as spicy or hot foods or alcohol may be helpful.

Therapies such as evening primrose oil, dong quai, ginseng, wild yam, magnet therapy, reflexology, and homeopathy have not been found more effective in treating hot flashes than placebo.²

Andrew M. Kaunitz, MD:
I would add soy isoflavones, red clover, and black cohosh to this list of therapies that have not been shown to be more effective than placebo.³

Phytoestrogens (such as equol), acupuncture, yoga, and hypnosis continue to be tested in randomized trials with mixed results.

Off-label drug options offer modest help. There are currently no FDA-approved nonhormonal pharmaceutical options for relief of hot flashes; the gold standard for treatment remains estrogen therapy. For moderate to severe bothersome hot flashes, potentially effective drug therapies used off label include clonidine, selective serotonin reuptake inhibitors (SSRIs), selective norepinephrine reuptake inhibitors (SNRIs), and gabapentin (TABLE 1).^2,4 In large, randomized, controlled trials, the following agents were modestly more effective than placebo: desvenlafaxine,⁵ low-dose paroxetine salt,⁶ escitalopram,⁷ and gastroretentive gabapentin.⁸ Participants in these trials included women with both spontaneous and surgically induced menopause.

Although sponsors have applied for approval for three of these agents, the FDA so far has declined to approve these agents for vasomotor treatment due to concerns about risks versus benefits. Benefits of these nonhormonal prescription therapies need to be weighed carefully against side effects, because the reduction in absolute hot flushes is modest.