Consenso. Parte I Guías para evaluación y tratamiento de depresión perimenopausica: recomendaciones / Consensus. Part I Guidelines for evaluation and treatment of perimenopausal depression: recommendations

Hay una nueva apreciación de la perimenopausia, definida como las etapas de transición temprana y tardía de la menopausia, también como la posmenopausia temprana, como una ventana de vulnerabilidad para el desarrollo de síntomas depresivos y episodios depresivos mayores. Sin embargo, las recomendaciones clínicas sobre cómo identificar, caracterizar y tratar la depresión clínica están faltando. Para abordar esta brecha, se convocó un panel de expertos para revisar sistemáticamente la literatura publicada y desarrollar lineamientos sobre la evaluación y manejo de la depresión perimenopáusica. Las áreas abordadas incluyeron: 1) epidemiología; 2) presentación clínica; 3) efectos terapéuticos de los antidepresivos; 4) efectos de la terapia hormonal; y 5) la eficacia de otras terapias (por ejemplo, psicoterapia, ejercicio y productos naturales para la salud). En general, la evidencia sugiere que la mayoría de las mujeres de mediana edad que experimentan un episodio depresivo mayor durante la perimenopausia han tenido un episodio previo de depresión. La depresión de la mediana edad se presenta con síntomas depresivos clásicos comúnmente en combinación con síntomas de la menopausia (es decir, síntomas vasomotores, trastornos del sueño) y problemas psicosociales. Los síntomas de la menopausia se complican, coexisten y se superponen con la presentación de la depresión. El diagnóstico implica la identificación de la etapa menopáusica, la evaluación de los síntomas psiquiátricos y de la menopausia (los cuales son concurrentes), apreciación de los factores psicosociales comunes en la mediana edad, diagnósticos diferenciales y el uso de pruebas de detección con instrumentos validadas. Las opciones terapéuticas probadas para la depresión (es decir, antidepresivos, psicoterapia) son la primera línea de tratamientos para la depresión perimenopáusica. Aunque la terapia con estrógenos no está aprobada para tratar la perimenopausia, existe evidencia de que tiene efectos antidepresivos en mujeres perimenopáusicas, particularmente en aquellas con síntomas vasomotores concomitantes. Los datos sobre estrógeno más progestina son escasos y no concluyentes.

There is a new appreciation of the perimenopause ­ defined as the early and late menopause transition stages as well as the early postmenopause - as a windowof vulnerability for the development of both depressive symptoms and major depressive episodes. However, clinical recommendations on how to identify, characterize and treat clinical depression are lacking. To address this gap, an expert panel was convened to systematically review the published literature and develop guidelines on the evaluation and management of perimenopausal depression. The areas addressed included: 1) epidemiology; 2) clinical presentation; 3) therapeutic effects of antidepressants; 4) effects of hormone therapy; and 5) efficacy of other therapies (eg, psychotherapy, exercise, and natural health products). Overall, evidence generally suggests that most midlife women who experience a major depressive episode during the perimenopause have experienced a prior episode of depression. Midlife depression presents with classic depressive symptoms commonly in combination with menopause symptoms (ie, vasomotor symptoms, sleep disturbance), and psychosocial challenges. Menopause symptoms complicate, co-occur, and overlap with the presentation of depression. Diagnosis involves identification of menopausal stage, assessment of co-occurring psychiatric and menopause symptoms, appreciation of the psychosocial factors common in midlife, differential diagnoses, and the use of validated screening instruments. Proven therapeutic options for depression (ie, antidepressants, psychotherapy) are the front-line treatments for perimenopausal depression. Although estrogen therapy is not approved to treat perimenopausal depression, there is evidence that it has antidepressant effects in perimenopausal women, particularly those with concomitant vasomotor symptoms. Data on estrogen plus progestin are sparse and inconclusive.

Guías para evaluación y tratamiento de depresión perimenopausica parte 2 / Guidelines for evaluation and treatment of perimenopausal depression: part2

Resumen Hay una nueva apreciación de la perimenopausia, definida como las etapas de transición temprana y tardía de la menopausia, también como la posmenopausia temprana, como una ventana de vulnerabilidad para el desarrollo de síntomas depresivos y episodios depresivos mayores. Sin embargo, las recomendaciones clínicas sobre cómo identificar, caracterizar y tratar la depresión clínica están faltando. Para abordar esta brecha, se convocó un panel de expertos para revisar sistemáticamente la literatura publicada y desarrollar lineamientos sobre la evaluación y manejo de la depresión perimenopáusica. Las áreas abordadas incluyeron: 1) epidemiología; 2) presentación clínica; 3) efectos terapéuticos de los antidepresivos; 4) efectos de la terapia hormonal; y 5) la eficacia de otras terapias (por ejemplo, psicoterapia, ejercicio y productos naturales para la salud). En general, la evidencia sugiere que la mayoría de las mujeres de mediana edad que experimentan un episodio depresivo mayor durante la perimenopausia han tenido un episodio previo de depresión. La depresión de la mediana edad se presenta con síntomas depresivos clásicos comúnmente en combinación con síntomas de la menopausia (es decir, síntomas vasomotores, trastornos del sueño) y problemas psicosociales. Los síntomas de la menopausia se complican, coexisten y se superponen con la presentación de la depresión. El diagnóstico implica la identificación de la etapa menopáusica, la evaluación de los síntomas psiquiátricos y de la menopausia (los cuales son concurrentes), apreciación de los factores psicosociales comunes en la mediana edad, diagnósticos diferenciales y el uso de pruebas de detección con instrumentos validadas. Las opciones terapéuticas probadas para la depresión (es decir, antidepresivos, psicoterapia) son la primera línea de tratamientos para la depresión perimenopáusica. Aunque la terapia con estrógenos no está aprobada para tratar la perimenopausia, existe evidencia de que tiene efectos antidepresivos en mujeres perimenopáusicas, particularmente en aquellas con síntomas vasomotores concomitantes. Los datos sobre estrógeno más progestina son escasos y no concluyentes.

Abstract There is a new appreciation of the perimenopause ­ defined as the early and late menopause transition stages as well as the early postmenopause - as a windowof vulnerability for the development of both depressive symptoms and major depressive episodes. However, clinical recommendations on how to identify, characterize and treat clinical depression are lacking. To address this gap, an expert panel was convened to systematically review the published literature and develop guidelines on the evaluation and management of perimenopausal depression. The areas addressed included: 1) epidemiology; 2) clinical presentation; 3) therapeutic effects of antidepressants; 4) effects ofhormonetherapy;and5)efficacyofothertherapies(eg,psychotherapy,exercise,andnatural health products). Overall, evidence generally suggests that most midlife women who experience a major depressive episode during the perimenopause have experienced a prior episode of depression. Midlife depression presents with classic depressive symptoms commonly in combination with menopause symptoms (ie, vasomotor symptoms, sleep disturbance), and psychosocial challenges. Menopause symptoms complicate, co-occur, and overlap with the presentation of depression. Diagnosis involves identification of menopausal stage, assessment of co-occurring psychiatric and menopause symptoms, appreciation of the psychosocial factors common in midlife, differential diagnoses, and the use of validated screening instruments. Proven therapeutic options for depression (ie, antidepressants, psychotherapy) are the front-line treatments for perimenopausal depression. Although estrogen therapy is not approved to treat perimenopausal depression, there is evidence that it has antidepressant effects in perimenopausal women particularly those with concomitant vasomotor symptoms. Data on estrogen plus progestin are sparse and inconclusive.

Anxiety as a risk factor for menopausal hot flashes: evidence from the Penn Ovarian Aging cohort.

OBJECTIVE: The aim of this study was to identify temporal associations of anxiety dimensions with menopausal hot flashes in women progressing through the menopausal transition. We hypothesized that associations of both somatic and affective dimensions of anxiety with hot flashes increased in the menopausal transition, and that somatic anxiety was an independent risk factor for menopausal hot flashes. METHODS: Hot flashes, anxiety symptoms, hormone levels, and other psychosocial variables were assessed annually for 14 years of follow-up. The 233 women were premenopausal at baseline and continued through 1 year or more after the final menstrual period. Anxiety dimensions were assessed with the Zung Anxiety Scale, a validated measure of affective anxiety and somatic anxiety. Summed item scores were divided by the number of items rated, so that ranges of the two dimensions were comparable. RESULTS: Seventy-two percent of the sample reported moderate/severe hot flashes during the 14-year interval. There was no significant interaction between anxiety dimensions and menopausal stages. When adjusted for menopausal stage, the magnitude of association between somatic anxiety and hot flashes, however, dramatically increased (odds ratio [OR], 3.03; 95% CI, 2.12-4.32; P < 0.001), whereas the association between affective anxiety and hot flashes increased to a lesser extent (OR, 1.27; 95% CI, 1.03-1.57; P = 0.024). Women with high levels of somatic anxiety (top third of the sample) had the greatest risk of hot flashes (P < 0.001). When the anxiety dimensions were considered in combination, the additive effect of high affective anxiety symptoms was minimal, with no significant difference between the group with high affective/low somatic symptoms and the low symptom group in incident hot flashes at each menopausal stage (P = 0.54). In multivariable analysis, somatic anxiety increased the risk of hot flashes more than three times (OR, 3.13; 95% CI, 2.16-4.53; P < 0.001), but affective anxiety was not significantly associated with hot flashes after adjustment for other study variables (OR, 1.19; 95% CI, 0.96-1.48; P = 0.117). Time-lagged somatic anxiety scores significantly predicted hot flashes, with a 71% increase in risk (OR, 1.71; 95% CI, 1.21-2.41; P = 0.002). Time-lagged affective anxiety scores did not predict hot flashes (OR, 1.06; 95% CI, 0.87-1.31; P = 0.58). CONCLUSIONS: This study showed a strong predictive association of somatic anxiety with the risk of menopausal hot flashes. The temporal associations suggest that somatic anxiety is not simply a redundant measure of hot flashes but predicts the risk of menopausal hot flashes and may be a potential target in clinical management of perimenopausal women.

Risk of long-term hot flashes after natural menopause: evidence from the Penn Ovarian Aging Study cohort.

OBJECTIVE: This study aims to estimate the risk of hot flashes relative to natural menopause and to evaluate the associations of hormone levels, behavioral variables, and demographic variables with the risk of hot flashes after menopause. METHODS: We performed annual assessment of 255 women who were premenopausal at baseline and reached natural menopause within 16 years of follow-up. RESULTS: The prevalence of moderate/severe hot flashes increased in each premenopausal year, reaching a peak of 46% in the first 2 years after the final menstrual period (FMP). Hot flashes decreased slowly after menopause and did not return to premenopausal levels until 9 years after the FMP. The mean (SD) duration of moderate/severe hot flashes after the FMP was 4.6 (2.9) years (for any hot flashes, 4.9 [3.1] y). One third of women at 10 years or more after menopause continued to experience moderate/severe hot flashes. African-American women (obese and nonobese) and obese white women had significantly greater risks of hot flashes compared with nonobese white women (interaction, P = 0.01). In multivariable analysis, increasing follicle-stimulating hormone levels before the FMP (P < 0.001), decreasing estradiol (odds ratio, 0.87; 95% CI, 0.78-0.96; P = 0.008), and increasing anxiety (odds ratio, 1.05; 95% CI, 1.03-1.06; P < 0.001) were significant risk factors for hot flashes, whereas higher education levels were protective (odds ratio, 0.66; 95% CI, 0.47-0.91; P = 0.011). CONCLUSIONS: Moderate/severe hot flashes continue, on average, for nearly 5 years after menopause; more than one third of women observed for 10 years or more after menopause have moderate/severe hot flashes. Continuation of hot flashes for more than 5 years after menopause underscores the importance of determining individual risks/benefits when selecting hormone or nonhormone therapy for menopausal symptoms.

Cigarettes, genetic background, and menopausal timing: the presence of single nucleotide polymorphisms in cytochrome P450 genes is associated with increased risk of natural menopause in European-American smokers.

OBJECTIVE: This study aims to evaluate associations between variations in genes involved in the metabolism of environmental chemicals and steroid hormones and risk of menopause in smokers. METHODS: Survival analysis was performed on 410 eligible participants from the Penn Ovarian Aging study (ongoing for 14 years), a cohort study of late-reproductive-age women. Single nucleotide polymorphisms at the following loci were studied: COMT Val158Met, CYP1B1*4 Asn452Ser, CYP1B1*3 Leu432Val, and CYP3A4*1B. RESULTS: Significant interactions between smoking and single nucleotide polymorphisms were observed in European-American carriers of CYP3A4*1B and CYP1B1*3, supporting a greater risk of menopause entry compared with those not carrying these alleles. Among CYP1B1*3 carriers, smokers had a greater risk of menopause entry than nonsmokers (adjusted hazard ratio [HR], 2.26; 95% CI, 1.4-3.67; median time to menopause, 10.42 and 11.07 y, respectively). No association between smoking and menopause was identified in CYP1B1 wild types. Among CYP3A4*1B carriers, smokers were at greater risk for menopause entry than nonsmokers (adjusted HR, 15.1; 95% CI, 3.31-69.2; median time to menopause, 11.36 and 13.91 y, respectively). Risk of menopause entry in CYP3A4 wild types who smoked was far lower (adjusted HR, 1.59; 95% CI, 1.03-2.44). Heavily smoking CYP1B1*3 carriers (adjusted HR, 3.0; 95% CI, 1.54-5.84; median time to menopause, 10.41 y) and heavily smoking CYP3A4*1B carriers (adjusted HR, 17.79; 95% CI, 3.21-98.65; median time to menopause, 5.09 y) had the greatest risk of menopause entry. CONCLUSIONS: Our finding that the risk of menopause entry in European-American smokers varies depending on genetic background represents a novel gene-environment interaction in reproductive aging.