Because vasomotor symptoms appear to be the result of estrogen withdrawal, rather than simply low estrogen levels, if cessation of estrogen therapy is desired, the dose should be reduced slowly over time. Abruptly stopping treatment may result in a return of disruptive vasomotor symptoms. This recommendation is based on clinical experience, as no controlled trials have been performed to examine the optimal way to cease hormone therapy use. One possible approach to stopping therapy is to reduce the dose and dosing interval slowly (e.g., every 2 or 3 months) and let the patient’s symptoms guide the pace at which she discontinues therapy.
When a woman chooses not to take estrogen or when it is contraindicated, other options are available (Table 34.2) (18). Progestin therapy alone is an option for some women. Medroxyprogesterone acetate (MPA; Provera) (20 mg per day) and megestrol acetate (Megace) (20 mg per day) effectively treat vasomotor symptoms (19,20). Several drugs that alter central neurotransmitter pathways are effective. Agents that decrease central noradrenergic tone, such as clonidine (Catapres), decrease hot ﬂashes, although the effect size is not great. Potential side effects include orthostatic hypotension and drowsiness.
Selective serotonin or serotonin norepinephrine reuptake inhibitors (SSRIs/SNRIs) are effective and are the mainstay of nonhormonal treatment of hot ﬂashes, although none are FDA approved for this purpose. In a double-blind, randomized, placebo-controlled trial of paroxetine CR (Paxil) (12.5 and 25 mg per day), menopausal women with hot ﬂashes experienced a significant reduction in both hot ﬂash frequency and severity (21). Actual hot ﬂash frequency decreased by 3.3 hot ﬂashes per day on paroxetine versus 1.8 on placebo, and the improvement in
Table 34.2 Options for the Treatment of Vasomotor Symptoms aNot U.S. Food and Drug Administration–approved for treatment of vasomotor symptoms.
vasomotor symptoms was independent of any significant change in mood or anxiety symptoms. The most common side effects were headache, nausea, and insomnia. Paroxetine is a potent inhibitor of the cytochrome P450 system (CYP2D6) required to convert tamoxifen to its active form. It should not be used in women with breast cancer who are receiving tamoxifen, as concurrent use may result in a higher rate of breast cancer recurrence. Venlafaxine (Effexor) (75 mg per day), an SNRI, significantly reduced hot ﬂashes in a controlled trial, though the active treatment group experienced significantly more side effects, including dry mouth, nausea, and anorexia (22). Most studies of SSRI or SNRI use for vasomotor symptoms are only short term and not all show an improvement in symptoms. In a double-blind, parallel-group trial of 9 months’ duration, there was no significant improvement in hot ﬂashes with either ﬂuoxetine (Prozac) or citalopram (Celexa) (10 to 30 mg per day) compared to placebo (23).