A 61-year-old woman is evaluated for hot flushes, which have been persistent for the last 10 years. They occur at least 7 times per day, last for approximately 60 seconds, and are associated with severe sweating, palpitations, and occasional nausea. She is awakened several times per night. She has tried herbal medications, including soy and black cohosh, but has not experienced any benefit. She has hypertension, type 2 diabetes mellitus, and hyperlipidemia. Five years ago, she developed deep venous thrombosis after hip replacement surgery. Her current medications are ramipril, metformin, atorvastatin, calcium, and vitamin D.
On physical examination, vital signs are normal. BMI is 29. The remainder of the examination is normal.
Which of the following is the most appropriate treatment?
B: Oral estrogen therapy
C: Oral estrogen/progesterone therapy
D: Topical (vaginal) estrogen
MKSAP Answer and Critique
The correct answer is E: Venlafaxine.
This 61-year-old woman with cardiovascular risk factors and a history of deep venous thrombosis should be started on a nonhormonal therapy for her hot flushes. Certain antidepressants, including serotonin-norepinephrine reuptake inhibitors such as venlafaxine, are effective nonhormonal medications for reducing menopausal vasomotor symptoms.
Approximately 10% of menopausal women experience hot flushes for 7 to 10 years after the cessation of menses. This patient is continuing to experience frequent and severe hot flushes which have been refractory to conservative therapy and are decreasing her quality of life; thus, pharmacologic therapy is warranted. Systemic estrogen therapy is the most effective treatment for the relief of menopausal hot flushes and must be coadministered with progesterone in women with an intact uterus. However, combined estrogen and progesterone therapy has been shown to increase the risk of several adverse outcomes, including coronary heart disease, stroke, invasive breast cancer, and venous thromboembolism. The North American Menopause Society guideline notes that women older than 60 years who experienced natural menopause at the median age and have never used hormone therapy will have elevated baseline risks of cardiovascular disease, venous thromboembolism, and breast cancer; hormone therapy, therefore, should not be initiated in this population without a compelling indication and only after appropriate counseling and attention to cardiovascular risk factors. Moreover, this patient has a history of deep venous thrombosis, which is an absolute contraindication to initiating hormone therapy.
Several nonhormonal medications have been found to be effective for the treatment of menopausal hot flushes. Notably, there is a significant placebo effect: in most studies, approximately one-third of women will experience relief of hot flushes, even if they do not receive active treatment. In numerous studies, venlafaxine, administered at doses of 37.5 mg/d to 150 mg/d, decreases hot flush severity and frequency in approximately 60% of patients (as compared with 30% who experienced benefit with placebo treatment). Paroxetine is similarly beneficial; in contrast, few studies have shown efficacy with fluoxetine or citalopram. Gabapentin and clonidine are two additional nonhormonal treatments that reduce hot flushes, but attendant side effects may limit their use in some patients.
Vaginal estrogen therapy is typically used for the isolated treatment of vaginal dryness, pruritus, and dyspareunia. Treatment with vaginal estrogen tablets will improve local vaginal symptoms, but will not improve menopausal vasomotor symptoms.
- Owing to cardiovascular and thromboembolic risks, systemic hormone therapy is not recommended for treatment of menopausal vasomotor symptoms in women older than 60 years who experienced menopause at the median age.
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