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Putting evidence into practice: Hot flashes

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Editor’s note: One in a series of articles on managing cancer-related symptoms from the Oncology Nursing Society.

Hot flashes, also known as hot flushes, vasomotor symptoms, night sweats, and menopausal symptoms, are significantly more frequent and severe in women diagnosed with breast cancer compared to women without the disease. Hot flashes are defined by Boekhout, Beijnen, and Schellens (2006) as “a subjective sensation of heat that is associated with objective signs of cutaneous vasodilation and a subsequent drop in core temperature” (p. 642). In addition to women with breast cancer, men treated for prostate cancer with androgen deprivation, hormone therapy, or surgical castration also experience frequent hot flashes and sweating.

Hot flashes rarely occur in the noncancer female population before the perimenopausal transition. However, cancer treatment, particularly for breast cancer, can cause an early onset of menopause or exacerbate existing menopausal symptoms (Kaplan, 2011). Hot flashes occur in about 78% of all breast cancer survivors (Fenlon, Corner, & Haviland, 2008; Jacobson et al., 2001; Savard, Savard, Quesnel, & Ivers, 2009), and 40% to 59% of women with cancer rate their hot flashes from moderate to severe (Stearns, 2004; Tremblay, Sheeran, & Aranda, 2008). For men, about 33% of the noncancer male population will experience hot flashes, with only half reporting that the symptoms are bothersome (Adelson, Loprinzi, & Hershman, 2005). However, incidence increases to 35% to 80% for men with advanced-stage prostate cancer who have been surgically or medically castrated (Frisk, 2010). Studies have shown that tamoxifen and aromatase inhibitors increase the severity and frequency of hot flashes, and hot flashes are the most commonly cited adverse effect associated with these agents (Howell et al., 2005).

Putting Evidence Into Practice

To promote nursing practice that is based on evidence, ONS launched the Putting Evidence Into Practice (PEP) program in 2005. ONS PEP teams consisting of advanced practice nurses, staff nurses, and a nurse scientist were charged with reviewing the literature to determine what treatments and interventions are proven to alleviate many cancer-related problems that are sensitive to nursing interventions. Each team classified interventions under the following categories: recommended for practice, likely to be effective, benefits balanced with harms, effectiveness not established, effectiveness unlikely, and not recommended for practice.

Likely to be effective

Although there are no items recommended for practice, two pharmacologic treatments are categorized as likely to be effective in the treatment of hot flashes. In order to be listed as likely to be effective, the intervention has to have demonstrated effectiveness from a single rigorously conducted controlled trial, have consistent supportive evidence from well-designed controlled trials using small samples, or have guidelines developed from evidence and supported by expert opinion.

Gabapentin: In two randomized, controlled trials (Loprinzi et al., 2009; Pandya et al., 2005) of gabapentin versus placebo in women with breast cancer, a significant difference was noted in the gabapentin (900 mg per day) arm. In addition, one randomized, controlled trial (Biglia et al., 2007) comparing gabapentin (900 mg per day) with vitamin E showed a significant difference in the gabapentin group.

Venlafaxine: A double-blind, placebo-controlled, randomized trial by Loprinzi et al. (2000) showed that venlafaxine effectively reduced hot flashes. The proposed dose was 75 mg per day. Loprinzi et al. (2000) included breast cancer survivors on tamoxifen and healthy women in the study. In addition, Buijs et al. (2009) and Loibl et al. (2007) compared venlafaxine to clonidine and found both to be effective in relieving hot flashes.

Effectiveness not established

A number of interventions are listed in the effectiveness not established category. These interventions have insufficient or conflicting data or data of inadequate quality current exist, with no clear indication of harm. A listing of pharmacologic as well as complementary and alternative treatment interventions are listed in Table 1.

Table 1. Pharmacologic and Nonpharmacologic Interventions

Pharmacologic

  • Clonidine
  • Estrogen-replacement therapy (for men)
  • Fluoxetine
  • Mirtazapine
  • Paroxetine
  • Progestin therapy
  • Sertraline
  • Stellate ganglion block
  • Testosterone replacement therapy
  • Tibolone

Complementary and Alternative Treatment Interventions

  • Acupuncture
  • Black cohosh
  • Hypnosis
  • Peer counseling
  • Relaxation therapy
  • Vitamin E
  • Yoga

Note. Based on information from Kaplan et al., 2011.

Effectiveness unlikely

For interventions in which a lack of effectiveness has been demonstrated, Kaplan et al. (2011) listed two entries.

Homeopathy: A randomized, controlled trial by Jacobs, Herman, Heron, Olsen, and Vaughters (2005) which stratified for age, breast cancer stage, and tamoxifen use, found no significant difference in hot flash activity in a one-year period when homeopathic remedies were used. In addition, two observational studies of homeopathic treatment on hot flashes reported improvement, but many flaws were noted in the studies and, therefore, were not considered useful (Clover & Ratsey, 2002; Thompson & Reilly, 2003).

Soy supplements: Four double-blind, controlled trials of soy supplements versus placebo to treat hot flashes in women with breast cancer (stratified for tamoxifen use) did not show a difference in hot flash symptoms between the two groups (MacGregor, Canney, Patterson, McDonald, & Paul, 2005; Nikander, Metsa-Heikkila, Ylikorkala, & Tiitinen, 2004; Quella et al., 2000; Van Patten, 2002). In addition, a randomized, controlled trial by Sharma et al. (2009) of men treated with androgen deprivation therapy for prostate cancer showed that soy isoflavones did not lead to a significant improvement in hot flashes compared to the placebo group.

Nursing Implications

Nurses are in a unique position to recognize those patients at risk for the development of hot flashes and should recognize the importance of addressing this symptom, as it can be disruptive to quality of life. Nurses also can advocate for these patients with physicians regarding the provision of medications that are, at least, likely to be effective. Finally, nurses have the opportunity to educate their patients regarding the potential effectiveness of various interventions in order to assist patients in making decisions about the use of pharmacologic or nonpharmacologic approaches.

Sean Pieszak is a staff editor in the Publications department at the Oncology Nursing Society in Pittsburgh, PA. More information about the ONS PEP classification for Hot Flashes can be found at http://www.ons.org/Research/PEP/HotFlashes.

Selected references

Adelson, K.B., Loprinzi, C.L., & Hershman, D.L. (2005). Treatment of hot flushes in breast and prostate cancer. Expert Opinion on Pharmacotherapy, 6, 1095-1106. doi:10.1517/14656566.6.7.1095

Biglia, N., Kubatzki, F., Sgandurra, P., Ponzone, R., Marenco, D., Peano, E., & Sismondi, P. (2007). Mirtazapine for the treatment of hot flushes in breast cancer survivors: A prospective pilot trial. Breast Journal, 13, 490–495. doi:10.1111/j.1524-4741.2007.00470.x

Boekhout, A.H., Beijnen, J.H., & Schellens, J.H.M. (2006). Symptoms and treatment in cancer therapy-induced early menopause. Oncologist, 11, 641–654. doi:10.1634/theoncologist.11-6-641

Buijs, C., Mom, C.H., Willemse, P.H., Marike Boezen, H., Maurer, J.M., Wymenga, A.N., Merits, M.J. (2009). Venlafaxine versus clonidine for the treatment of hot flashes in breast cancer patients: A double-blind, randomized cross-over study. Breast Cancer Research and Treatment, 115, 573–580. doi:10.1007/s10549-008-0138-7

Clover, A., & Ratsey, D. (2002). Homeopathic treatment of hot flushes: A pilot study. Homeopathy, 91, 75–79.

Fenlon, D.R., Corner, J.L., & Haviland, J.S. (2008). A randomized controlled trial of relaxation training to reduce hot flashes in women with primary breast cancer. Journal of Pain and Symptom Management, 35, 397–405. doi:10.1016/j.jpainsymman.2007.05.014

Frisk, J. (2010). Managing hot flushes in men after prostate cancer—A systematic review. Maturitas, 65, 15-22.

Howell, A., Cuzick, J., Baum, M., Buzdar, A., Dowsett, M., Forbes, J.F., ATAC Trialists’ Group. (2005). Results of the ATAC (arimidex, tamoxifen, alone or in combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet, 365, 60-62. doi:10.1016/S0140-6736(04)17666-6

Jacobs, J., Herman, P., Heron, K., Olsen, S., & Vaughters, L. (2005). Homeopathy for menopausal symptoms in breast cancer survivors: A preliminary randomized controlled trial. Journal of Alternative and Complementary Medicine, 11, 21–27. doi:10.1089/acm.2005.11.21

Jacobson, J.S., Troxel, A.B., Evans, J., Klaus, L., Vahdat, L., Kinne, D., Grann, V.R. (2001). Randomized trial of black cohosh for the treatment of hot flashes among women with a history of breast cancer. Journal of Clinical Oncology, 19, 2739–2745.

Kaplan, M. (2011). Hot flashes. In L.H. Eaton, J.M. Tipton, and M. Irwin (Eds.), Putting Evidence Into Practice: Improving oncology patient outcomes (2nd ed., pp. 31-37). Pittsburgh, PA: Oncology Nursing Society.

Kaplan, M., Mahon, S., Cope, D., Hill, S., Keating, E., & Jacobson, M. (2011). Hot flashes: What interventions are effective in preventing and treating hot flashes in people with cancer? In L.H. Eaton, J.M. Tipton, and M. Irwin (Eds.), Putting Evidence Into Practice: Improving oncology patient outcomes (2nd ed., pp. 39-48). Pittsburgh, PA: Oncology Nursing Society.

Loibl, S., Schwedler, K., von Minckwitz, G., Strohmeier, R., Mehta, K.M., & Kaufmann, M. (2007). Venlafaxine is superior to clonidine as treatment of hot flashes in breast cancer patients—A double-blind, randomized study. Annals of Oncology, 18, 689–693. doi:10.1093/annonc/mdl478

Loprinzi, C.L., Kugler, J.W., Sloan, J.A., Mailliard, J.A., LaVasseur, B.I., Barton, D.L., Christensen, B.J. (2000). Venlafaxine in management of hot flashes in survivors of breast cancer: A randomised controlled trial. Lancet, 356, 2059–2063. doi:10.1016/S0140-6736(00)03403-6

Loprinzi, C.L., Sloan, J., Stearns, V., Slack, R., Iyengar, M., Diekmann, B., Novotny, P. (2009). Newer antidepressants and gabapentin for hot flashes: An individual patient pooled analysis. Journal of Clinical Oncology, 27, 2831–2837. doi:10.1200/JCO.2008.19.6253

MacGregor, C.A., Canney, P.A., Patterson, G., McDonald, R., & Paul, J. (2005). A randomised double-blind controlled trial of oral soy supplements versus placebo for treatment of menopausal symptoms in patients with early breast cancer. European Journal of Cancer, 41, 708–714. doi:10.1016/j.ejca.2005.01.005

Nikander, E., Metsa-Heikkila, M., Ylikorkala, O., & Tiitinen, A. (2004). Effects of phytoestrogens on bone turnover in postmenopausal women with a history of breast cancer. Journal of Clinical Endocrinology and Metabolism, 89, 1207–1212. doi:10.1016/j.ejca.2005.01.005

Pandya, K.J., Morrow, G.R., Roscoe, J.A., Zhao, H., Hickok, J.T., Pajon, E., Flynn, P.J. (2005). Gabapentin for hot flashes in 420 women with breast cancer: A randomised double-blind placebo-controlled trial. Lancet, 366, 818–824. doi:10.1016/S0140-6736(05)67215-7

Quella, S.K., Loprinzi, C.L., Barton, D.L., Knost, J.A., Sloan, J.A., LaVasseur, B.I., Novotny, P.J. (2000). Evaluation of soy phytoestrogens for the treatment of hot flashes in breast cancer survivors: A North Central Cancer Treatment group trial. Journal of Clinical Oncology, 18, 1068–1074. Retrieved from http://jco.ascopubs.org/content/18/5/1068.long

Savard, M.H., Savard, J., Quesnel, C., & Ivers, H. (2009). The influence of breast cancer treatment on the occurrence of hot flashes. Journal of Pain and Symptom Management, 37, 687-697. doi:10.1016/j.jpainsymman.2008.04.010

Sharma, P., Wisniewski, A., Braga-Basaria, M., Xu, X., Yep, M., Denmeade, S., Basaria, S. (2009). Lack of an effect of high dose isoflavones in men with prostate cancer undergoing androgen deprivation therapy. Journal of Urology, 182, 2265–2272. doi:10.1016/j.juro.2009.07.030

Stearns, V. (2004). Management of hot flashes in breast cancer survivors and men with prostate cancer. Current Oncology Reports, 6, 285-290.

Thompson, E.A., & Reilly, D. (2003). The homeopathic approach to the treatment of symptoms of oestrogen withdrawal in breast cancer patients: A prospective observational study. Homeopathy, 92, 131–134.

Tremblay, A., Sheeran, L., & Aranda, S.K. (2008). Psychoeducational interventions to alleviate hot flashes: A systematic review. Menopause, 15, 193-202. doi:10.1097/gme.0b013e3180c08dc

Van Patten, C.L. (2002). Effect of soy phytoestrogens on hot flashes in postmenopausal women with breast cancer: A randomized, controlled clinical trial. Journal of Clinical Oncology, 20, 1449–1455. doi:10.1200/JCO.20.6.1449

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