Sweats and Hot Flashes
Hormone replacement therapy
Estrogen replacement effectively controls hot flashes associated with biologic or treatment-associated postmenopausal states in women. The proposed mechanism of action of estrogen replacement on hot flash amelioration is by raising the core body temperature sweating threshold;[Level of evidence: I] however, many women have relative or absolute contraindications to estrogen replacement. Physicians and breast cancer survivors often think there is an increased risk of breast cancer recurrence or de novo breast malignancy with hormone replacement therapies and defer hormonal management of postmenopausal symptoms. Methodologically strong data evaluating the risk of breast cancer associated with hormone replacement therapy in healthy women have been minimal, despite strong basic science considerations suggesting the possibility of such a risk.
In May 2002, the Women's Health Initiative (WHI), a large, randomized, placebo-controlled trial of the risks and benefits of estrogen plus progestin in healthy postmenopausal women, was stopped prematurely at a mean follow-up of 5.2 years (�1.3) because of the detection of a 1.26-fold increased breast cancer risk (95% confidence interval [CI], 1.00-1.59) in women receiving hormone replacement therapy. Tumors among women in the hormone replacement therapy group were slightly larger and more advanced than in the placebo group, with a substantial and statistically significant rise in the percentage of abnormal mammograms at first annual screening; such a rise might hinder breast cancer diagnosis and account for the later stage at diagnosis.[14,15][Level of evidence: I] These results are supported by a population-based case-control study suggesting a 1.7-fold (95% CI, 1.3-2.2) increased risk of breast cancer in women using combined hormone replacement therapy. The risk of invasive lobular carcinoma was increased 2.7-fold (95% CI, 1.7-4.3), the risk of invasive ductal carcinoma was increased 1.5-fold (95% CI, 1.1-2.0), and the risk of estrogen receptor-positive/progesterone receptor-positive breast cancer was increased 2.0-fold (95% CI, 1.5-2.7). Increased risk was highest for invasive lobular tumors and in women who used hormone replacement therapy for longer periods of time. Risk was not increased with unopposed estrogen therapy.
The very limited data available do not indicate an increased risk of breast cancer recurrence with single-agent estrogen use in patients with a history of breast cancer.[17,18] A series of double-blind placebo-controlled trials suggests that low-dose megestrol acetate (i.e., 20 mg by mouth twice a day) and selective serotonin reuptake inhibitors (SSRIs) are among the more promising agents for hot flash management in this population. Limited data suggest that brief cycles of intramuscular depot medroxyprogesterone acetate also play a role in the management of hot flashes.[Level of evidence: I] Risk associated with progestin use is unknown.