Estrogen was first approved by the FDA for the treatment of menopausal symptoms in 1942, and for many decades estrogen replacement therapy had been widely prescribed for peri- and post-menopausal women. In 2002, however, data from the Women’s Health Initiative (WHI) suggested that hormonal therapy may be associated with an increased risk of breast cancer and cardiovascular disease. These findings have led to a dramatic decrease in the use of hormone replacement therapy (HRT), with many women abruptly discontinuing its use.

After discontinuing hormone therapy, many women experience recurrent menopausal symptoms, including hot flushes, night sweats and sleep disturbance (Ness et al, 2006). Even when HRT is tapered gradually, these symptoms may recur. Women may also experience mood symptoms and other symptoms including anxiety, agitation, and irritability subsequent to hormone discontinuation. Although there is limited data regarding the prevalence of mood symptoms among women who discontinue HRT, it is likely that women who have a history of peri-menopausal mood changes may be particularly vulnerable to depression in the setting of HRT discontinuation (Stewart et al, 2004).

In a preliminary study conducted at the Center for Women’s Mental Health, Drs. Claudio Soares and Hadine Joffe have examined the efficacy of paroxetine CR (controlled release) for the treatment of peri- and postmenopausal women who had recently discontinued hormone therapy. In this study, 64 peri- and post-menopausal women (age 40-60 years) who experienced the emergence of significant vasomotor symptoms (VMS) and other somatic complaints after the discontinuation of hormone therapy were recruited. Most of the women had initiated hormone therapy to alleviate vasomotor symptoms and sleep disruption and had discontinued hormone therapy (median duration of use = 77 months) primarily because of concerns regarding the long-term safety of HRT. While subjects with mild depressive symptoms were considered eligible for the study, those with any Axis I psychiatric disorder (assessed with the Mini-International Neuropsychiatric Interview, MINI), moderate to severe symptoms of depression (MADRS scores > 19) and/or significant anxiety (HAM-A scores > 17) were excluded. Subjects entered a one-week, single blind, placebo lead-in phase. Placebo non-responders (<30% decline in VMS, n=56) entered into a six-week, double-blind phase and were randomized to receive either paroxetine CR 12.5 mg/day (n=28) or placebo (n=28). Dosing was adjusted up to 25 mg/day after two weeks, based on treatment response and tolerability. Subjects were re-evaluated after 1, 2, and 6 weeks.

Treatment with paroxetine CR resulted in significant reduction of vasomotor and mood symptoms in peri- and postmenopausal women who became symptomatic after discontinuing hormone therapy. Treatment was well tolerated. These findings are consistent with previous studies that have demonstrated a significant reduction in the severity of vasomotor symptoms in non-depressed women treated with serotonergic antidepressants (Stearns et al, 2003; Evans et al, 2005) and demonstrate that therapy with paroxetine CR may be helpful for the treatment of both mood and physical symptoms following the discontinuation of hormone therapy.

Ruta Nonacs, MD PhD

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Ness J, Aronow WS, Beck G. Menopausal symptoms after cessation of hormone replacement therapy. Maturitas 2006;53(3):356-61.

Stearns V, Beebe KL, Iyengar M, Dube E. Paroxetine controlled release in the treatment of menopausal hot flashes: a randomized controlled trial. JAMA. 2003; 289(21):2827-34.

Stewart DE, Rolfe DE, Robertson E. Depression, Estrogen, and the Women’s Health Initiative. Psychosomatics 2004; 45:445-447.