What is Effective and Safe for Night Sweats in Women with Breast Cancer?
Question
I'm 47 and wringing the sheets every night with hot flushes. I went into menopause early because of chemotherapy for breast cancer and then had surgery to take out my uterus and ovaries because I have the bad gene (BRCA). I'm now taking the new drug that blocks estrogen production but is making my flushes worse. I've tried soymilk, tofu and all kinds of plant estrogens. I'm afraid of herbs because I'm told they may increase estrogen and therefore feed my cancer. And I've tried acupuncture-it helps about a week and then I need another treatment.
Right now I'm fighting taking the newer anti-depressant my doctor prescribed-I'm not depressed. She says that medicine is what the Cancer Agency recommends for hot flushes. I asked my pharmacist and got a printout of its side effects-it causes sleep problems and loss of appetite. I already have them! And I've heard they are only likely to be 60-70% effective.
My question is, can I try something that will help my night sweats without making me at risk my breast cancer will return? Or should I consider stopping the estrogen blocker-I don't want to because, although it is making my flushes worse, it will prevent another bout of breast cancer. Or am I stuck feeling as wrung out as my sheets for the next dozen years?
Answer
Thank you for your question. It is a very good one.
Let me first tell you that you are not alone in having both bad night sweats and breast cancer. Vasomotor symptoms (meaning night and daytime hot flushes) are probably more common for women with breast cancer. The reasons for this may be multiple-one is that the brains of women with breast cancer may have been exposed to more estrogen than for women without it-the likely reason is genetic differences in the internal metabolism of estrogen. Then premenopausal women go into menopause more abruptly with the ovary-damaging effects of chemotherapy-and, for some, like yourself, the ovaries are removed surgically. For menopausal women with breast cancer, they are often on hormone therapy that is suddenly stopped making flushes worse. We know from women without breast cancer that the most severe hot flushes occur in premenopausal women who have early, induced menopause (through surgery, chemotherapy or irradiation). It is an abrupt decrease in estrogen level (for women whose brains have previously been exposed to high levels) that seems to cause hot flushes.
We are beginning to understand the key role that stress hormones play in hot flushes. (This is relevant to all women, but particularly to a woman with breast cancer-more on that in a minute). For example, women with regular daytime hot flushes that were randomized (assigned by chance) to two different monitoring sessions had fewer flushes during a 4-hour session that was soothing and non-stressful compared to their own flushes during a 4-hour session interrupted with noise, violence and chaos (2). We also know that during a hot flush there is increased production of brain and other stress hormones (like norepinephrine from the brain and cortisol from the adrenal glands) (3;4). I know that I felt angry (in fact, furious) when I suddenly wakened in what was my first night sweat-and those emotions occurred before I even started to sweat!
A couple connections we're just learning about between hot flushes and daily life relate to common things like being too heavy and smoking. Several studies have now shown that those who smoke are more likely to have hot flushes (5;6) perhaps because smoking is used to deal with stress. Being overweight also increases your likelihood of hot flushes (5;6), especially during perimenopause (before you've been a year without a period)(6). If you are a smoker, ask your physician to support you though some of the many potential strategies to help you stop. At the same time, if you are too heavy, start an exercise programme so that you can gradually reduce to a normal weight.
Although you were not adequately helped by soy and acupuncture, adding various strategies together will begin to decrease your hot flush severity so you can cope. Interestingly, just believing that you can cope with night sweats, will itself, decrease the problem that night sweats cause you (7). Soy beverage compared with a similar tasting rice drink (without any phytoestrogens) both reduced hot flushes by about 40% in a randomized three month trial (8). Acupuncture twice a week in men with prostate cancer who had surgical removal of their testicles, decreased hot flushes by 70% in a non-blinded or randomized study (9). Exercise, if it causes relaxation or decreases stress, will likely improve hot flushes by at least 50% based on a single small randomized trial (10). Finally, and most importantly, any form of meditation, relaxation, mindfulness or yoga breathing will significantly improve hot flushes (11;12). Rather than thinking that each of these alone will be sufficient, try starting one, then add on an additional strategy. These are all healthy things to do anyway-so add them successively until you're doing soy, acupuncture, exercise and regular yoga breathing/relaxation.
Now back to the unique issues for a woman with breast cancer. We already said that having a night sweat is associated with a sudden burst of stress hormones. The ones from the adrenal glands (like DHEA, and other weak male hormone-like ones) are converted into estrogen by your body. The "estrogen blocker" you described is probably one of the aromatase inhibitor medications that has recently been shown to decrease recurrent breast cancer more than tamoxifen (the anti-estrogen medication that has been the important therapy for the last 20 years) (13). If the night sweats cause release of hormones that can be made into estrogen and feed your cancer, it strikes me as essential for your breast cancer, as well as your quality of life, that your night sweats be effectively treated.
The severe sweating hot flushes, like the ones waking you every night, are the most resistant to any of our current hot flush therapies. Therefore, although I've gone to some length to encourage you to try multiple strategies, it is possible that they will not be sufficient to prevent your waking several nights a week. If that is the case, and you find that you're still tired, not sleeping and awake with sweating, I think that you need something more effective, not only for your energy but also to prevent breast cancer recurrence.
I suggest that you ask your family doctor for oral micronized progesterone therapy (Prometrium) in a dose of 300 mg every night. This suggestion is likely to be controversial because many breast cancer specialists believe that progesterone or its synthetic cousins (called progestins) cause breast cancer. They think that because estrogen alone in women who had hysterectomy (14) didn't increase breast cancer in the Women's Health Initiative trial but estrogen with low dose medroxyprogesterone did (15). This is not a fair comparison, however, because the women who had hysterectomy have lower ovarian blood flow, lower hormone levels and a lower breast cancer risk (16). And medroxyprogesterone, although similar, is not natural progesterone. Recent evidence from a 10-year study in over 100,000 menopausal women showed that progesterone prevented the 20% increased risk from breast cancer that estrogen alone caused (17). In the same study, women treated with estrogen with various progestins (including medroxyprogesterone) had an 80% increased breast cancer risk (17). These results fit with earlier studies showing that progesterone treatment caused breast cells to become more mature and stop growing even when progesterone was combined with estrogen (18;19). Therefore I think that progesterone is safe in a woman with breast cancer.
What makes me think it will be effective? I know it will help, because it has been effective for me and for many of my patients. Importantly, progesterone also significantly improves deep sleep (20). In terms of proper studies, progesterone as a cream (20 mg twice a day) given to menopausal women significantly improved hot flushes over one year compared with a placebo (21). In addition, many randomized controlled studies from the 1980s and 1990s have shown that progestins improve hot flushes. We recently documented a similar effectiveness for hot flushes of medroxyprogesterone and estrogen in a randomized, double blind trial in women who started either treatment when leaving the hospital after a premenopausal surgery that removed their ovaries (22). Although medroxyprogesterone would treat your night sweats, we can't be sure that it is safe for someone like you who has had breast cancer. Progesterone may help hot flushes and decrease breast cancer recurrence because it also decreases anxiety by being converted to calming hormones in the brain (23).
We performed a randomized double-blind placebo-controlled trial of progesterone for severe hot flushes in menopausal women, showing that this treatment is effective.
In summary, severe hot flushes not only cause fatigue and sleep disturbance, they also increase stress hormones. Increased stress hormones are now known to increase breast cancer risk (because many of them can be converted into estrogen by the body). Although there are many life style and alternative strategies that, singly or together, will decrease hot flushes, severe night sweats may not be sufficiently improved. If that is the case, oral micronized progesterone is a good option, is safe for a woman with treated breast cancer, and should be highly effective.
Hope this is helpful for you.
All the best,
Dr. Jerilynn C. Prior
Reference List
- Loprinzi CL, Kugler JW, Sloan JA, Mailliard JA, LaVasseur BI, Barton DL et al. Venlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial. Lancet 2000; 356(9247):2059-2063.
- Swartzman LC, Edelberg R, Kemmann E. Impact of stress on objectively recorded menopausal hot flushes and on flush report bias. Health Psychology 1990; 9:529-545.
- Freedman RR. Biochemical, metabolic, and vascular mechanisms in menopausal hot flashes. Fertil Steril 1998; 70(2):332-337.
- Genazzani AR, Petraglia F, Fachinetti F, Facchini V, Volpe A, Alessandrini G. Increase of proopiomelanocortin-related peptides during subjective menopausal flushes. Am J Obstet Gynecol 1984; 149(7):775-779.
- Gold EB, Sternfeld B, Kelsey JL, Brown C, Mouton C, Reame N et al. Relation of demographic and lifestyle factors to symptoms in a multi-racial/ethnic population of women 40-55 years of age. Am J Epidemiol 2000; 152:463-473.
- Whiteman MK, Staropoli CA, Langenberg PW, McCarter RJ, Kjerulff KH, Flaws JA. Smoking, body mass, and hot flashes in midlife women. Obstet Gynecol 2003; 101(2):264-272.
- Nedstrand E, Wijma K, Lindgren M, Hammar M. The relationship between stress-coping and vasomotor symptoms in postmenopausal women. Maturitas 1998; 31(1):29-34.
- Van Patten CL, Olivotto IA, Chambers GK, Gelman KA, Hislop TG, Templeton E et al. Effect of soy phytoestrogens on hot flashes in postmenopausal women with breast cancer: a randomized, controlled clinical trial. J Clin Oncol 2002; 20:1449-1455.
- Hammar M, Frisk J, Grimas O, Hook M, Spetz AC, Wyon Y. Acupuncture treatment of vasomotor symptoms in men with prostatic carcinoma: a pilot study. J Urol 1999; 161(3):853-856.
- Lindh-Astrand L, Nedstrand E, Wyon Y, Hammar M. Vasomotor symptoms and quality of life in previously sedentary postmenopausal women randomised to physical activity or estrogen therapy. Maturitas 2004; 48(2):97-105.
- Wijma K, Melin A, Nedstrand E, Hammar M. Treatment of menopausal symptoms with applied relaxation: a pilot study. J Behav Ther Exp Psychiatry 1997; 28(4):251-261.
- Freedman RR, Woodward S. Behavioral treatment of menopausal hot flushes: evaluation by ambulatory monitoring. Am J Obstet Gynecol 1991; 167:436-439.
- Baum M, Budzar AU, Cuzick J, Forbes J, Houghton JH, Klijn JG et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet 2002; 359(9324):2131-2139.
- Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA 2004; 291(14):1701-1712.
- Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in health postmenopausal women: prinicpal results from the Women's Health Initiative Randomized Control trial. JAMA 2002; 288:321-333.
- Kreiger N, Sloan M, Cotterchio M, Kirsh V. The risk of breast cancer following reproductive surgery. Eur J Cancer 1999; 35:97-101.
- Fournier A, Berrino F, Clavel-Chapelon F. Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study. Breast Cancer Res Treat 2008; 107(1):103-111.
- Chang KJ, Lee TTY, Linares-Cruz G, Fournier S, de Lignieres B. Influence of percutaneous administration of estradiol and progesterone on human breast epithelial cell cycle in vivo. Fertil Steril 1995; 63:785-791.
- Foidart J, Collin C, Denoo X, Desreux J, Belliard A, Fournier S et al. Estradiol and progesterone regulate the proliferation of human breast epithelial cells. Fertil Steril 1998; 5:963-969.
- Friess E, Tagaya H, Trachsel L, Holsboer F, Rupprecht R. Progesterone-induced changes in sleep in male subjects. Am J Physiol 1997; 272:E885-E891.
- Leonetti HB, Longo S, Anasti JN. Transdermal progesterone cream for vasomotor symptoms and postmenopausal bone loss. Obstet Gynecol 1999; 94:225-228.
- Prior JC, Nielsen JD, Hitchcock CL, Williams LA, Vigna YM, Dean CB. Medroxyprogesterone and conjugated oestrogen are equivalent for hot flushes: a 1-year randomized double-blind trial following premenopausal ovariectomy. Clin Sci (Lond) 2007; 112(10):517-525.
- Bitran D, Shiekh M, McLeod M. Anxiolytic effect of progesterone is mediated by the neurosteroid allopregnanolone at brain GABAA receptors. J Neuroendocrinol 1995; 7(3):171-177.
Updated Date:
Tuesday, November 19, 2013 - 13:15