October 2022

Spanish translation:
Soares-Jr JM, Espósito Sorpreso IC, Nunes Curado JF, Ferreira Filho ES, Dos Santos Simões R, Bonfá E, Silva CA, Baracat EC.
Efecto de la terapia hormonal en pacientes menopáusicas con lupus eritematoso sistémico: una revisión sistemática.
Climacteric. 2022;25(5):427-433. doi: 10.1080/13697137.2022.2050205.

Resumen:
El lupus eritematoso sistémico (LES) afecta principalmente a las mujeres, que pueden necesitar terapia hormonal (TH) en la menopausia. Sin embargo, existe cierta preocupación en cuanto a su eficacia y seguridad. Esta revisión sistemática tuvo como objetivo determinar el efecto de la TH sobre la actividad del LES y su seguridad. El estudio fue una revisión sistemática cualitativa. La investigación se realizó con datos extraídos de las bases de datos Embase, MEDLINE y Cochrane utilizando términos MESH hasta abril de 2021, sin restricción de fecha o idioma. Dieciséis estudios fueron seleccionados para el análisis. La mayoría de ellos mostró que la TH es eficaz en el tratamiento de los síntomas de la menopausia sin impacto en la actividad del LES, pero un ensayo clínico aleatorizado mostró un aumento en el número de eventos trombóticos. La presente revisión sistemática demostró la eficacia de la TH para el tratamiento de los síntomas menopáusicos de las pacientes con LES. El riesgo de exacerbación de síntomas de LES y trombosis parece ser muy bajo.

Palabras claves: Lupus eritematoso sistémico; Terapia de reemplaz o hormonal; Terapia hormonal; menopausia.

Spanish translation:
Ruan X, Mueck AO.
Elección primaria de estrógeno y progestágeno como componentes para la TRH: una visión farmacológica clínica.
Climacteric. 2022;25(5):443-452. doi: 10.1080/13697137.2022.2073811.

Resumen:
La prescripción de la terapia de reemplazo hormonal (TRH) requiere considerar la selección de sus dos componentes, el estrógeno y el progestágeno. En cuanto al estrógeno, la decisión es principalmente si se usa estradiol (E2) o estrógenos equinos conjugados (EEC). Estos son los componentes necesarios para tratar eficazmente los síntomas del climaterio y/o prevenir la osteoporosis, actualmente las únicas indicaciones etiquetadas. Aún existe controversia sobre las dosis adecuadas comparando E2 y EEC; sin embargo, el consenso es que las diferencias en la eficacia de E2 y EEC no son un problema real. Por lo tanto, se deben utilizar otros criterios. La primera razón para agregar el progestágeno es evitar el desarrollo de cáncer de endometrio (es decir, lograr la ‘seguridad endometrial’). Cualquier preparación de TRH ‘fija-combinada’ disponible tiene que ser probada para determinar la eficacia endometrial suficiente, porque la primera pregunta que hacen las autoridades sanitarias antes del registro del producto se relaciona con la seguridad endometrial. En general, podemos confiar en la seguridad endometrial de estos productos combinados fijos. Sin embargo, puede ser que queramos usar combinaciones ‘libres’, que son necesarias si usamos E2 transdérmico (parches, gel, spray), pero también para individualizar horarios, por ejemplo, al tratar problemas de sangrado. La pregunta aquí es cómo obtener conocimiento sobre la eficacia endometrial de los diferentes progestágenos y cómo monitorear la terapia. Intentaremos responder a estas dos preguntas desde el punto de vista de la ‘farmacología clínica’, como disciplina que considera preferentemente las propiedades farmacológicas, pero también relacionadas con la práctica clínica, para conseguir una terapia individualizada con una eficacia óptima, la mejor tolerabilidad y los mínimos riesgos.

Palabras claves: Estrógeno; Terapia de reemplazo hormonal; elección farmacológica; progestágeno

Spanish translation:
Zouboulis CC, Blume-Peytavi U, Kosmadaki M, Roí E, Vexiau-Robert D, Kerob D, Goldstein SR. Piel,
Cabello y más allá: el impacto de la menopausia.
Climacteric. 2022;25(5):434-442. doi: 10.1080/13697137.2022.2050206.

Resumen:
La piel es un órgano endocrino y un objetivo importante de hormonas como los estrógenos, los andrógenos y el cortisol. Además de los síntomas vasomotores (SVM), los síntomas de la piel y el cabello a menudo reciben menos atención que otros síntomas de la menopausia a pesar de tener un efecto negativo significativo en la calidad de vida. Los síntomas menopáusicos de la piel y las mucosas incluyen sequedad y prurito, adelgazamiento y atrofia, arrugas y flacidez, mala cicatrización de heridas y reducción de la vascularización, mientras que las lesiones premalignas y malignas de la piel y los signos de envejecimiento de la piel son causados casi exclusivamente por factores ambientales, especialmente la radiación solar. Los síntomas capilares de la menopausia incluyen reducción del crecimiento capilar y la densidad en el cuero cabelludo (efluvio difuso debido a la rarefacción folicular y/o alopecia androgenética de patrón femenino), alteración de la calidad y la estructura del cabello, y aumento del crecimiento del vello no deseado en las áreas faciales. La terapia de reemplazo hormonal (TRH) no está indicada solo para síntomas de la piel y el cabello debido al balance riesgo-beneficio, pero los beneficios potenciales más amplios de la TRH (más allá del efecto del estrógeno sobre los SVM, los huesos, las mamas, el corazón y los vasos sanguíneos) que incluyen en la piel, el cabello y las mucosas deben discutirse con las mujeres para que sean capaz de tomar las mejores posibles decisiones informadas sobre cómo prevenir o manejar sus síntomas menopáusicos.

Palabras claves: Menopausia; exposoma; cabello; terapia de reemplazo hormonal; hormonas; mucosa; perimenopausia; piel.

Spanish translation:
Wang XY, Wang LH, Di JL, Zhang XS, Zhao GL.
Asociación de estado y síntomas menopáusicos con síntomas depresivos en mujeres chinas de mediana edad.
Climacteric. 2022;25(5):453-459. doi: 10.1080/13697137.2021.1998435.

Resumen:
Objetivo: Este estudio tuvo como objetivo examinar la asociación del estado y los síntomas de la menopausia con los síntomas depresivos.
Métodos: Fue una encuesta transversal basada en la comunidad que reclutó a 6,745 mujeres de 40 a 55 años de edad en las regiones oriental, central y occidental de China en 2018. El estado menopáusico se clasificó en etapa reproductiva, perimenopausia o postmenopausia según la clasificación del Taller de Etapas del Envejecimiento Reproductivo. Los síntomas menopáusicos se determinaron mediante el índice menopáusico de Kupperman modificado y se clasificaron como ninguno (puntuación total < 15), leves (puntuación total entre 15 ≥ y ≤ 24) o moderados a graves (puntuación total ≥ 25). Se utilizaron modelos de regresión logística para examinar las asociaciones del estado y los síntomas de la menopausia con los síntomas depresivos evaluados por el Cuestionario #9 de Salud del Paciente.
Resultados: La prevalencia de síntomas depresivos entre mujeres en etapa reproductiva, perimenopausia y postmenopausia fue de 15.4%, 23.9% y 22.8%, respectivamente. Después del ajuste multivariable, la perimenopausia (odds ratio [OR] = 1.21, intervalo de confianza [IC] del 95%: 1.01-1.47) y la postmenopausia (OR = 1.28, IC del 95%: 1.04-1.58) se asociaron con un mayor riesgo de síntomas depresivos que durante la etapa reproductiva. Los síntomas menopáusicos leves (OR = 5.55, IC del 95%: 4.68-6.59) y de moderados a graves (OR = 14.77, IC del 95%: 10.94-19.94) se asociaron con una mayor probabilidad de síntomas depresivos en comparación con el grupo que no informó síntomas menopáusicos. síntomas.
Conclusiones: El estado y los síntomas de la menopausia se asociaron de forma independiente con el riesgo de síntomas depresivos en mujeres chinas de mediana edad.

Palabras claves: Síntomas menopáusicos; síntomas depresivos; menopausia; perimenopausia; postmenopausia.

Spanish translation:
Zhang Y, Fu WQ, Liu NN, Liu HJ.
Alteraciones de la homogeneidad regional en la perimenopausia: un estudio de resonancia magnética funcional en estado de reposo.
Climacteric. 2022;25(5):460-466. doi: 10.1080/13697137.2021.2014808.

Resumen:
Objetivo: Se utilizó la homogeneidad regional (HoRe) para evaluar los cambios de la función cerebral y la relación con la función cognitiva en mujeres perimenopáusicas.
Métodos: El estudio transversal reclutó a 25 mujeres perimenopáusicas y 25 mujeres postmenopáusicas que se sometieron a mediciones del nivel de hormonas sexuales, evaluaciones clínicas y neuropsicológicas y exploraciones por imágenes de resonancia magnética (IRM). La HoRe se midió en función de los datos de resonancia magnética funcional en estado de reposo (RMF-ER) y se compararon las diferencias en HoRe entre los grupos perimenopáusicos y postmenopáusicos. Se extrajeron los valores de volumen de materia gris (VMG) de las regiones cerebrales con diferencias (región de interés [RDI]) en HoRe y se compararon las diferencias de VMG entre los dos grupos. Analizamos las correlaciones de los valores HoRe y VMG de estos RDI con los resultados de los niveles de hormonas sexuales, evaluaciones clínicas y neuropsicológicas en los dos grupos.
Resultados: Los valores de HoRe en la circunvolución lingual izquierda y la circunvolución precentral derecha aumentaron en la perimenopausia, mientras que los valores de HoRe en la circunvolución temporal inferior izquierda y el putamen bilateral disminuyeron. El análisis de correlación mostró que los valores de HoRe del giro temporal inferior izquierdo se correlacionaron positivamente con el tiempo de reacción de la prueba de palabra de color de Stroop en mujeres perimenopáusicas.
Conclusiones: Los cambios en los patrones anormales de la HoRe en mujeres perimenopáusicas afectan la función cognitiva. Estos cambios en la función cerebral pueden proporcionar más conocimientos e información sobre los mecanismos neurales de la disfunción cognitiva en mujeres perimenopáusicas.

Palabras claves: Homogeneidad regional; función cognitiva; resonancia magnética funcional; perimenopausia.

• The relationship between obesity and bone metabolism is controversial.
• In recent decades, the protective role of obesity in the development of osteoporosis has been questioned.

• This was an observational longitudinal prospective cohort study of postmenopausal women with obesity (O) (body mass index (BMI) > 30 kg/m²) and non-obesity (NoO) (BMI < 30 kg/m2).
• A total of 250 postmenopausal women were included in the study (NoO: 124 (49.6%) and O: 126 (50.4%)).
• Measured variables included epidemiological, dietary (calcium intake, vitamin D intake, smoking, alcohol consumption, and physical activity), biochemicals (β-crosslap, type I procollagen amino-terminal peptide (P1NP), 25OH-vitamin D, and parathyroid hormone (PTH)), anthropometrics, and fracture data five years after the start of the study.

• The mean age was 56.17 (3.91) years.
• Women with obesity showed lower levels of vitamin D (O: 17.27 (7.85) ng/mL, NoO: 24.51 (9.60) ng/mL; p &lt; 0.01), and higher levels of PTH (O: 53.24 (38.44-65.96) pg/mL, NoO: 35.24 (25.36-42.40) pg/mL; p &lt; 0.01).
• Regarding the bone formation marker (P1NP), it was found to be high in women without obesity, O: 45.46 (34.39-55.16) ng/mL, NoO: 56.74 (45.34-70.74) ng/mL; p &lt; 0.01; the bone resorption marker (β-crosslap) was found to be high in women with obesity, being significant in those older than 59 years (O: 0.39 (0.14) ng/mL, NoO 0.24 (0.09) ng/mL; p &lt; 0.05).
• No differences were observed in the risk of fracture at 5 years based on BMI (OR = 0.90 (95%CI 0.30-2.72); p = 0.85).

• The study was a qualitative systematic review.
• Research was conducted with data retrieved from Embase, MEDLINE and Cochrane databases using MESH terms up to April 2021, with no bar on date or language.

• Sixteen studies were selected for analysis.
• Most of them showed HT to be effective in the treatment of menopausal symptoms with no impact in SLE activity, but one randomized clinical trial showed an increase in the number of thrombotic events.

• The present systematic review demonstrated the efficacy of HT for treating the menopausal symptoms of SLE patients.
• The risk of flare and thrombosis seems to be very low.

• Evidence from animal studies suggests that the gradual rise in follicle-stimulating hormone (FSH) during reproductive senescence may contribute to the change in adiposity distribution characteristic of menopause.
• The potential independent role the interrelationships of FSH and estradiol (E2) may play in postmenopausal adiposity changes are not well studied.

• In cross-sectional analyses, FSH levels were inversely associated with all measures of adiposity in models adjusted for age, years since menopause, smoking status, pack-years, and hormone therapy (HT) use; these associations were not influenced by adjustment for serum E2.
• In longitudinal analyses, the subset of women who discontinued HT over follow-up (n = 242) experienced the largest increase in FSH (+33.9 mIU/mL) and decrease in E2 (-44.3 pg/mL) and gains in all adiposity measures in unadjusted analyses.
• In adjusted analyses, an increase in FSH was associated with a gain in percentage of total body fat, total body fat mass, and subcutaneous adipose tissue (SAT).

• While cross-sectional findings suggest that FSH is inversely associated with adiposity, our longitudinal findings suggest that greater increases in FSH were associated with greater increases in percentage of total body fat, total body fat mass, and SAT.
• Future studies are needed to provide additional insight into FSH-adiposity mechanisms in larger samples.

• Postmenopausal women were categorized according to age at menopause and self-reported reason for menopause in a cross-sectional analysis of 6,870 women.
• Variables associated with the timing of menopause and hormone measurements of 17β-estradiol and follicle-stimulating hormone were explored using multivariable logistic regression analysis.
• Specific immunoprecipitating assays of steroidogenic autoantibodies against 21-hydroxylase (21-OH), side-chain cleavage enzyme (anti-SCC) and 17alpha-hydroxylase (17 OH), as well as NACHT leucine-rich-repeat protein 5 were used to identify women with likely autoimmune POI.

• Premature menopause was identified in 2.8% of women, and these women had higher frequencies of nulliparity (37.4% vs 19.7%), obesity (28.7% vs 21.4%), osteoporosis (17.1% vs 11.6%), hormone replacement therapy (59.1% vs 36.9%) and never smokers (60.1% vs 50.9%) (P < 0.05), compared to women with menopause ≥40 years.
• Iatrogenic causes were found in 91 (47%) and non-ovarian causes in 27 (14%) women, while 77 (39%) women were classified as POI of unknown cause, resulting in a 1.1% prevalence of idiopathic POI.
• After adjustments nulliparity was the only variable significantly associated with POI (odds ratio 2.46; 95% CI 1.63-3.42).
• Based on the presence of autoantibodies against 21 OH and SCC, 4.5% of POI cases were of likely autoimmune origin.

• Idiopathic POI affects 1.1% of all women and almost half of the women with premature menopause.
• Autoimmunity explains 4.5% of these cases judged by positive steroidogenic autoantibodies.

• A total of 5269 eligible postmenarcheal women, including 2411 premenopausal and 2858 menopausal women, were recruited from among the Tehran Lipid and Glucose Study.
• Cox proportional hazards regression model with adjustment of potential confounders was performed to assess the relationship between duration of EEE and incident of any hospitalized fractures.

• A total of 26.7% (1409/5269) women were menopausal at the baseline, and 2858 of the remaining participants reached menopause at the end of follow-up.
• Results of the unadjusted model demonstrated that the EEE z-score was negatively associated with fracture incidence [unadjusted hazard ratio (HR) 0.81, 95% CI 0.68-0.96] in postmenarchal women, indicating that per 1-SD increase of EEE z-score, the hazard of fracture reduced by 19%.
• Results remained statistically unchanged after adjustment for potential confounders (adjusted HR 0.70, 95% CI 0.58-0.86).

• The incidence of dyslipidemia increases after menopause.
• Menopause hormone therapy (MHT) is recommended for menopause related disease; however, it is benefit for lipid profiles is inconclusive.

• Related articles were searched on PubMed/Medline, EMBASE, Web of Science, and Cochrane Library databases from inception to December 2020.
• Data extraction and quality evaluation were performed independently by two reviewers.
• The methodological quality was assessed using the “Cochrane Risk of Bias checklist”.

• Seventy-three eligible studies were selected.
• The results showed that MHT significantly decreased the levels of TC (WMD: -0.43, 95% CI: -0.53 to -0.33), LDL-C (WMD: -0.47, 95% CI: -0.55 to -0.40) and LP (a) (WMD: -49.46, 95% CI: -64.27 to -34.64) compared with placebo or no treatment.
• Oral MHT led to a significantly higher TG compared with transdermal MHT (WMD: 0.12, 95% CI: 0.04-0.21).
• The benefits of low dose MHT on TG was also concluded when comparing with conventional-dose estrogen (WMD: -0.18, 95% CI: -0.32 to -0.03).
• The results also showed that conventional MHT significantly decreased LDL-C (WMD: -0.35, 95% CI: -0.50 to -0.19), but increase TG (WMD: 0.42, 95%CI: 0.18-0.65) compared with tibolone.
• When comparing with the different MHT regimens, estrogen (E) + progesterone (P) regimen significantly increased TC (WMD: 0.15, 95% CI: 0.09 to 0.20), LDL-C (WMD: 0.12, 95% CI: 0.07-0.17) and Lp(a) (WMD: 44.58, 95% CI:28.09-61.06) compared with estrogen alone.

• MHT plays a positive role in lipid profile in postmenopausal women, meanwhile for women with hypertriglyceridemia, low doses or transdermal MHT or tibolone would be a safer choice.
• Moreover, E + P regimen might blunt the benefit of estrogen on the lipid profile.

• This was a cross-sectional study carried out in 52 women who were treated from January 2014 to December 2019 in 2 public and private DIE surgical centers in Toulouse.
• All women answered the Menopausal Quality of Life questionnaire (MenQOL).
• Mean MenQOL scores were compared according to age at BO, smoking, BMI, level of education, delay between BO and the survey and post-BO hormone replacement therapy (HRT) using Mann-Whitney and Anova tests.
• Spearman’s correlation coefficient was used to analyze the correlations between all the MEnQOL domain scores and clinical variables.
• The variables associated with the outcomes in univariate analyses with p < 0.2 were jointly evaluated using multiple linear regression.

• The mean age at the time of the survey was 43.4 ± 3.4 years while the mean age at BO was 40.5 ± 3.4 years.
• The mean MenQOL score was 3.96 (± 1.45), with the highest scores in the sexual (4.77) and vasomotor (4.01) domains.
• BMI and smoking were independently and significantly associated with the mean total MenQOL score, all domain scores being significantly higher in overweight/obese women.
• A trend towards worse MenQOL scores was found in patients who had BO before the age of 41.
• The authors did not find any difference according to whether or not they were taking HRT.

• This is a first study evaluating quality of life in a specific population of oophorectomized women under the age of 45 using MenQOL for DIE.
• While BO is effective in relieving pain in women with severe DIE, the induced premature menopause is associated with a poor quality of life, which deserves further attention.

• The was a retrospective cohort study subjects that comprised two groups.
• The COC group included 55 women who took low-dose COC for at least one year to control vasomotor symptoms.
• Another 55 women who had annual checkups without history of COC use served as controls.
• BMD and bone turnover markers were assessed periodically.

• In the control group, 12-month BMD values at the lumbar spine (LS) and total hip (TH) significantly decreased with a greater magnitude at LS, and bone resorption (BR) and formation (BF) markers increased concurrently with a larger change in BR. COCs increased BMD at LS after 12 months and prevented BMD decline at TH.
• Multivariable linear regression revealed a significant difference in LS BMD between groups at 12 months.
• In the COC group, there were significant negative correlations between baseline BMD and Z-score at LS and corresponding changes at 12 months.
• COCs did not alter BR markers, whereas BF markers were significantly decreased at 3 months.
• Group comparison at 12 months, as tested with adjusted linear regression, disclosed significant differences in both BR and BF makers.

• Bone loss associated with activated bone turnover is evident during the menopausal transition, and COCs might prevent BMD decrease and suppress bone turnover markers in perimenopausal Korean women.
• Significant increase in LS BMD and decreases in BF makers suggest underlying mechanisms of greater impact on BF.

• Data were obtained from the China Health and Retirement Longitudinal Study.
• Using the case-control matching method, 3,218 paired postmenopausal women and men matched for age and education were selected.
• Memory was assessed using the three-word recall task and a self-rated question.
• Poisson regression models with a robust error variance were used.

• The relative risk was 1.22 (95% confidence interval 1.08-1.38) for objective memory impairment in women compared with men (23.87% vs. 27.36%), and 1.51 (1.36-1.67) for subjective memory impairment (39.34% vs. 28.25%) after adjusting the confounders.
• The higher risk of objective memory impairment in women was different among groups of age at menarche in a linear pattern, with younger age at menarche associated with higher risks of objective memory impairment (p < 0.001 for trend).
• It was also different among groups of menopausal age and reproductive period in an approximate U-shaped pattern, with a similar risk of objective memory with men in women menopause at 52-53 years and having a reproductive period of 31-33 years and higher risks in women with earlier or later menopause (RRs raging form 1.17 to1.41) and a shorter or longer period of reproduction (RR, 1.23-1.29).
• The higher risks of subjective memory impairment in women were not different among different groups of reproductive factors.

• Postmenopausal women were at an increased risk of objective and subjective memory impairment than men.
• The higher risks in objective memory, but not subjective memory, were varied by age at menarche, age at menopause, and reproductive periods, which may help understand the underlying mechanisms of sex differences in cognitive ageing and guide precise intervention to preventing dementia among older women and men.

• The authors undertook a retrospective cohort study using routinely collected computerized medical records from the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) primary care database.
• They identified a cohort of 1,863,478 women over 18 years of age from 465 general practices in England.
• Mixed-effects logistic regression models were used to quantify the association between HRT or COCP use and all-cause mortality among women diagnosed with confirmed or suspected COVID-19 in unadjusted and adjusted models.

• There were 5,451 COVID-19 cases within the cohort. HRT was associated with a reduction in all-cause mortality in COVID-19 (adjusted OR 0.22, 95% CI 0.05 to 0.94).
• There were no reported events for all-cause mortality in women prescribed COCPs.
• This prevented further examination of the impact of COCP.

• The authors found that HRT prescription within 6 months of a recorded diagnosis of COVID-19 infection was associated with a reduction in all-cause mortality.
• Further work is needed in larger cohorts to examine the association of COCP in COVID-19, and to further investigate the hypothesis that oestrogens may contribute a protective effect against COVID-19 severity.