Age at natural menopause among patients with systemic lupus erythematosus.

OBJECTIVE: The aim of this study was to estimate the age at natural menopause in women with SLE. METHODS: One thousand and thirty-nine consecutive SLE patients <60 years of age were surveyed. Demographic and clinical data were queried by a single investigator. SLE characteristics and co-morbidities were retrieved from their medical records. Natural menopause was defined as amenorrhoea ≥12 months in the absence of previous hysterectomy, CYC exposure and severe chronic kidney disease (SCKD). Pregnant women and those with menses during the 12 months prior to interview were considered premenopausal. Median age at menopause was estimated by both logit and survival analyses. In addition, mean age at menopause was calculated for patients aged ≥40 years. Factors associated with age at natural menopause were assessed by Cox regression analysis. RESULTS: A total of 961 SLE women were analysed. At interview, most patients (81.6%) were premenopausal, 7.9% had natural menopause, 6.3% were postmenopausal previously exposed to CYC, 4.1% had undergone hysterectomy before menopause and 0.1% presented with SCKD and amenorrhoea. The mean age at interview was 35.2 years (s.d. 10.1), the mean age at SLE diagnosis was 26.9 years (s.d. 8.6) and the mean duration of disease was 8.2 years (s.d. 7.1). The mean recalled age at menopause was 46.4 years (s.d. 4.7). Median age at menopause estimated by logit and survival analyses were 50.7 and 50.8 years, respectively. Only the age at SLE diagnosis was associated with age at natural menopause. CONCLUSION: Median age at natural menopause in women with lupus is 50 years. This is consistent with the age at menopause reported in the general population.

Side effects unrelated to disease activity and acceptability of highly effective contraceptive methods in women with systemic lupus erythematosus: a randomized, clinical trial.

OBJECTIVES: To assess the side effects unrelated to disease activity and the acceptability of combined oral contraceptives (COCs), progestin-only pills (POPs) and copper-releasing intrauterine devices (IUDs) in women with systemic lupus erythematosus (SLE). STUDY DESIGN: A randomized clinical trial including 162 women with SLE, assigned to COC (n=54), POP (n=54) or IUD (n=54). Follow-up visits were conducted after 1, 2, 3, 6, 9 and 12 months of treatment to monitor the presence of symptoms, changes in body weight and blood pressure as well as the development of health problems other than those relating to lupus. Reasons for discontinuation and satisfaction with the use of the assigned method were recorded at the end of treatment. Statistical analysis included descriptive statistics, repeated measure analyses and Kaplan-Meier curves. RESULTS: Significantly different discontinuation rates due to any reason [35%, 55%, 29% (p<0.01)] or nonmedical reasons [(11%, 31%, 4% (p<0.05)] were observed among the COC, POP and IUD groups. Nausea was most frequent among COC users, dysmenorrhea among IUD users and acne and hirsutism among POP users. Mean blood pressures remained unchanged. Mild increases in body weight were observed over time in all treatment groups. Most women were satisfied with the use of the assigned contraceptive method. CONCLUSIONS: Oral contraceptives and IUD are acceptable birth control methods for patients with lupus, when counseling and specialized health attention are provided; however, the acceptability of POP appears to be inferior. Side effects unrelated to lupus disease activity are not frequent reasons to discontinue the contraceptive methods. IMPLICATIONS: This study delves into an area that has not been explored among patients with lupus. Our findings on the associated side effects and reasons for discontinuing COCs, POPs or copper-bearing IUDs may be useful in improving contraceptive counseling for women with lupus. Furthermore, they also heighten our knowledge on the reasons that may preclude the widespread use of effective contraceptives among lupus patients.

Efficacy of estrogen plus progestin on menopausal symptoms in women with systemic lupus erythematosus: a randomized, double-blind, controlled trial.

OBJECTIVE: To define the effects of continuous sequential estrogen plus progestin therapy on menopausal symptoms in women with systemic lupus erythematosus (SLE). METHODS: We performed a randomized, double-blind, 24-month clinical trial involving 106 women with SLE who were in the menopausal transition or early or late postmenopause. Patients received continuous sequential estrogen plus progestin (n = 52) or placebo (n = 54). Menopausal symptoms were assessed using the Greene Climacteric Scale at 0, 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 months. A new factor analysis of the scale reduced 21 items to 5 factors. The primary outcome was improvement of menopausal symptoms throughout the followup period. Results were analyzed by the intent-to-treat principle. RESULTS: At baseline, demographic and disease characteristics were similar in both groups. Fifteen of 21 menopausal symptoms had a prevalence of ≥50%, with a similar distribution between groups. Vasomotor factor scores decreased over time in both groups (P = 0.002), but in the estrogen plus progestin group the reduction was more pronounced than in the placebo group (1.5-2.0 versus 0.35-0.8 points on a scale of 0-6; P = 0.03). Maximum effects were observed among the most symptomatic women. Psychological, subjective-somatic, and organic-somatic factors scores also improved along time (P < 0.001), but the treatment and placebo arms improved to a similar degree. Thromboses occurred in 3 patients receiving estrogen plus progestin and in 1 patient receiving placebo. CONCLUSION: Menopausal symptoms are highly prevalent in peri- and postmenopausal lupus patients. Estrogen plus progestin improved vasomotor symptoms at a clinically significant level, but not other menopausal symptoms. Given the thrombotic risks of menopausal hormone therapy, this should be used only in women with significant vasomotor symptoms.

Menopause hormonal therapy in women with systemic lupus erythematosus.

OBJECTIVE: To evaluate the effects of menopause hormonal therapy on disease activity in women with systemic lupus erythematosus (SLE). METHODS: We conducted a double-blind, randomized clinical trial involving 106 women with SLE who were in the menopausal transition or in early or late postmenopause. Patients received a continuous-sequential estrogen-progestogen regimen (n = 52) or placebo (n = 54). Disease activity was assessed at baseline and at 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 months, according to the SLE Disease Activity Index (SLEDAI). The primary outcome measure was global disease activity, estimated by measuring the area under the SLEDAI curve. Secondary outcome measures included maximum SLEDAI score, change in SLEDAI score, incidence of lupus flares, median time to flare, medication use, and adverse events. Results were studied using intent-to-treat analysis. RESULTS: At baseline, demographic and disease characteristics were similar in both groups. Mean +/- SD SLEDAI scores were 3.5 +/- 3.3 and 3.1 +/- 3.4 in the menopause hormonal therapy and placebo groups, respectively (P = 0.57). Disease activity remained mild and stable in both groups throughout the trial. There were no significant differences between the groups in global or maximum disease activity, incidence or probability of flares, or medication use. Median time to flare was 3 months in both groups. Thromboses occurred in 3 patients who received menopause hormonal therapy and in 1 patient who received placebo. One patient in each group died during the trial due to sepsis. CONCLUSION: Menopause hormonal therapy did not alter disease activity during 2 years of treatment. However, an apparently increased risk of thrombosis seems to be a real threat in women with SLE who receive menopausal hormone therapy.

Autoantibodies against the fibrinolytic receptor, annexin 2, in antiphospholipid syndrome.

The association of thrombosis and gestational morbidity with antiphospholipid antibodies is termed antiphospholipid syndrome (APS). Annexin 2 (A2) is a profibrinolytic endothelial cell surface receptor that binds plasminogen, its tissue activator (tPA), and beta(2)-glycoprotein I (beta2GPI), the main antigen for antiphospholipid antibodies. Here, we evaluate A2 as a target antigen in APS. Serum samples from 434 individuals (206 patients with systemic lupus erythematosus without thrombosis, 62 with APS, 21 with nonautoimmune thrombosis, and 145 healthy individuals) were analyzed by enzyme-linked immunosorbent assay (ELISA) and immunoblot for antiphospholipid and A2 antibodies. Anti-A2 antibodies (titer > 3 SDs) were significantly more prevalent in patients with APS (22.6%; venous, 17.5%; arterial, 34.3%; and mixed thrombosis, 40.4%) than in healthy individuals (2.1%, P < .001), patients with nonautoimmune thrombosis (0%, P = .017), or patients with lupus without thrombosis (6.3%, P < .001). Anti-A2 IgG enhanced the expression of tissue factor on endothelial cells (6.4-fold +/- 0.13-fold SE), blocked A2-supported plasmin generation in a tPA-dependent generation assay (19%-71%) independently of beta2GPI, and inhibited cell surface plasmin generation on human umbilical vein endothelial cells (HUVECs) by 34% to 83%. We propose that anti-A2 antibodies contribute to the prothrombotic diathesis in antiphospholipid syndrome.

A trial of contraceptive methods in women with systemic lupus erythematosus.

BACKGROUND: The effects of estrogen-containing contraceptives on disease activity in women with systemic lupus erythematosus have not been determined. METHODS: We conducted a single-blind clinical trial involving 162 women with systemic lupus erythematosus who were randomly assigned to combined oral contraceptives, a progestin-only pill, or a copper intrauterine device (IUD). Disease activity was assessed at 0, 1, 2, 3, 6, 9, and 12 months according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). The primary outcome was global disease activity, which we estimated by measuring the area under the SLEDAI curve. Secondary outcomes included the maximum SLEDAI score, change in SLEDAI score, incidence of lupus flares, median time to first flare, systemic lupus erythematosus treatment, and adverse events. The results were analyzed by the intention-to-treat method. RESULTS: At baseline, all demographic features and disease characteristics were similar in the three groups. The mean (+/-SD) SLEDAI score was 6.1+/-5.6 in the group assigned to combined oral contraceptives, 6.4+/-4.6 in the group assigned to the progestin-only pill, and 5.0+/-5.3 in the group assigned to the IUD (54 patients in each group) (P=0.36). Disease activity remained mild and stable in all groups throughout the trial. There were no significant differences among the groups during the trial in global or maximum disease activity, incidence or probability of flares, or medication use. The median time to the first flare was three months in all groups. Thromboses occurred in four patients (two in each of the two groups receiving hormones), and severe infections were more frequent in the IUD group. One patient receiving combined oral contraceptives died from amoxicillin-related severe neutropenia. CONCLUSIONS: Global disease activity, maximum SLEDAI score, incidence of flares, time to first flare, and incidence of adverse events were similar among women with systemic lupus erythematosus, irrespective of the type of contraceptive they were using.

[Prevalence of anti-Chlamydia trachomatis and anti-Neisseria gonorrhoeae antibodies in Mexican populations]. / Prevalencia de anticuerpos anti-Chlamydia trachomatis y anti-Neisseria gonorrhoeae en grupos de individuos de la población mexicana.

OBJECTIVE: To estimate the prevalence of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infection in groups of individuals at different risks of sexually transmitted infections (STI). MATERIAL AND METHODS: Between January 1992 and December 1993, a cross-sectional multicentric study was carried out at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (National Institute of Medical Sciences and Nutrition "Salvador Zubirán") in Mexico City. The study population consisted of 945 reproductive age subjects (585 females and 360 males). Low and high risk groups were classified according to their risk for STI. High risk groups included infertile women with tubal damage, women with a history of ectopic pregnancy or abortion, infertile men, HIV/AIDS patients, homo- or bisexual men, and female commercial sex workers. Low risk groups included primigravidae, fertile men, and infertile women with no tubal damage. Serum anti-NG and anti-CT IgG and IgA were determined, in duplicate by immune-enzymatic assay, using as antigens NG pili and the LI fraction of CT. Descriptive analysis is presented as percentages. RESULTS: NG prevalence in females was 13.7% by IgG and 14.3% by IgA. CT prevalence was 11.4% by IgG and 4.4% by IgA. In males, NG prevalences were 3.3% and 13.3% by IgG and IgA, respectively; CT prevalences were 7.2% and 5.5%, respectively. In commercial sex workers, NG prevalences were 31.2% by IgG and 28.4% by IgA, and CT 25.0% and 5.7% by IgG and IgA, respectively. In women with infertility due to tubal damage the prevalences of NG were 5.6% and 9.8%, respectively, and those of CT were 8.4% and 1.4%, respectively. In 110 young primigravid NG prevalences were 4.5% and 10.0%, respectively, and CT 3.6% and 9.1%. CONCLUSIONS: These data confirm the high prevalence of Neisseria gonorrhoeae and Chlamydia trachomatis in female commercial sex workers and homo- or bisexual men, but not in other high-risk groups like infertile women or women with a history of ectopic pregnancy or abortion. The English version of this paper is available at:http://www.insp.mx/salud/index.html.

Prevalencia de anticuerpos anti-Chlamydia trachomatis y anti-Neisseria gonorrhoeae en grupos de individuos de la población mexicana / Prevalence of antibodies against Chlamydia trachomatis and Neisseria gonorrhoeae in Mexican populations

OBJETIVO: Estimar la prevalencia de infección por Chlamydia trachomatis (CT) y Neisseria gonorrhoeae (NG) en grupos de individuos con diferente riesgo para infecciones de transmisión sexual. MATERIAL Y MÉTODOS: Estudio transversal multicéntrico efectuado en el Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, de la Ciudad de México, de enero de 1992 a diciembre de 1993, en el que se estudiaron 945 individuos en edad reproductiva, 585 mujeres y 360 hombres. Según su riesgo para infecciones de transmisión sexual se clasificaron en grupos de alto y bajo riesgo. Los de alto riesgo incluyeron mujeres infértiles con daño tubario, mujeres con embarazo ectópico o aborto, hombres infértiles, pacientes con VIH/SIDA, hombres homo o bisexuales y trabajadoras del sexo comercial (TSC). Los de bajo riesgo: mujeres primigestas, hombres fértiles y mujeres infértiles sin daño tubario. Se determinó en duplicado IgG e IgA anti-NG y anti-CT en suero, por análisis inmunoenzimático, utilizando como antígeno el pili de NG y la fracción L1 de CT. Se calcularon porcentajes. RESULTADOS: En mujeres la prevalencia para NG fue IgG 13.7 por ciento e IgA 14.3 por ciento, y para CT fue IgG 11.4 por ciento e IgA 4.4 por ciento. En hombres, NG 3.3 por ciento y 13.3 por ciento, respectivamente, y para CT 7.2 por ciento y 5.5 por ciento, respectivamente. En TSC se encontró NG en 31.2 por ciento y 28.4 por ciento, respectivamente, y para CT 25.0 por ciento y 5.7 por ciento, respectivamente. En mujeres con infertilidad por daño tubario, NG 5.6 por ciento y 9.8 por ciento, respectivamente, y CT 8.4 por ciento y 1.4 por ciento, respectivamente. En 110 primigestas jóvenes, NG 4.5 por ciento y 10.0 por ciento, respectivamente, y CT 3.6 por ciento y 9.1 por ciento, respectivamente. CONCLUSIONES: Estos datos confirman la prevalencia elevada de Neisseria gonorrhoeae y Chlamydia trachomatis en trabajadoras del sexo comercial y en hombres homo/bisexuales, pero no en otros grupos de alto riesgo como las mujeres infértiles, con aborto o embarazo ectópico.

El climaterio / The climacteric

"El presente capítulo tiene por objeto revisar los conceptos actuales en relación con la demografía, epidemiología y mecanismos del climaterio, así como su repercusión sobre la sexualidad. El climaterio es el período durante el cual se presenta la regresión de la función ovárica, es decir, la transición de la etapa reproductiva a la no reproductiva, siendo la menopausia (último sangrado uterino) su signo más relevante. La menopausia, determinada genéticamente ocurre alrededor de los 50 años, mientras que el climaterio se extiende por un período de aproximadamente 30 años. Recientemente el estudio del climaterio ha adquirido mayor importancia debido a que con el incremento en la esperanza de vida a nivel mundial el número de mujeres posmenopáusicas ha aumentado en forma significativa, principalmente en los países en desarrollo, condicionando la aparición de situaciones médicas y socio-económicas que demandan atención multidisciplinaria. Endocrinológicamente el climaterio se caracteriza por la depleción de folículos ováricos y la disminución o cese de la producción de estradiol y progesterona, manteniéndose sólo la de andrógenos. Secundariamente las gonadotrofinas se incrementan. El síndrome climatérico es producto de la deprivación hormonal y sus síntomas varían dependiendo de la etapa que se considere. En la premenopáusica sobresalen las alteraciones menstruales y algunas de tipo emocional, mientras que en la posmenopausia aparecen los síntomas más clásicos como bochornos, insomnio, inestabilidad emocional y atrofia génito-urinaria. La osteoporosis y la ateroesclerosis se aceleran con la deprivación estrogénica y pueden dar lugar a fracturas patológicas y a enfermedad coronaria, respectivamente. La sexualidad también sufre cambios durante el climaterio. Si bien se ha sugerido un aumento transitorio del interés sexual, la mayor parte de los estudios indican deterioro de la actividad y deseo sexuales, desconociéndose los mecanismos involucrados en dicho fenómeno. Hasta ahora no se ha demostrado una relación directa entre los estrógenos y la sexualidad, por lo que la mejoría observada con la administración de estrógenos se atribuye en parte a la mejoría de la atrofia génito-urinaria. La terapia estrogénica de reemplazo es útil para controlar la sintomatología vasomotora, prevenir la atrofia génito-urinaria, la osteoporosis, y probablemente el incremento del riesgo cardiovascular. Su principal desventaja es que conlleva a mayor riesgo para la hiperplasia y adenocarcinoma de endometrio, que pueden ser prevenidos con la adición de una progestina. El dilema es que la progestina potencialmente puede revertir el efecto cardioprotector de los estrógenos. Existen diversas formulaciones estrogénicas y progestinas, así como vías y esquemas para su adminmistración. Sus ventajas y desventajas son objeto de amplia evaluación a nivel mundial. Sin embargo, la terapia de reemplazo es sólo uno de los aspectos que se deben considerar en el manejo integral del climaterio, ya que otros factores emocionales, nutricionales y socio-económicos pueden ser también de gran relevancia"

Eficacia de anticonceptivos inyectables en mujeres mexicanas / Efficacy of injectable contraceptives in Mexican women

De 1978 a 1981 se evaluó la eficacia de dos anticonceptivos inyectables, acetato de medroxiprogesterona de depósito (AMPD) y enantato de noretisterona (EN-NET), en una problación de 326 mujeres mexicanas cuyas edades fluctuaron entre los 18 y 40 años. Las participantes, sanas y de fecundidad comprobada, se dividieron en tres grupos a los que se administró por vía intramuscular 150 mg de AMPD cada 90 días, 200 mg de EN-NET cada 60 días primero y después cada 84 días, y 200 mg de EN-NET cada 60 días respectivamente. El índice de deserción acumulativo al final del ensayo fue de 78% y el motivo más frecuente de abandono fue primero la pérdida de seguimiento y, segundo, las alteraciones en el patrón de sangrado mentrual. Durante el estudio solo ocurrió un embarazo en los tres grupos en una mujer del grupo 2. Por otra parte el incremento promedio en el peso corporal fue moderado (4 kg) y en ningún caso se citó como causa para abandonar el tratamiento. Tampoco se observó un cambio significativo en la tensión arterial. Se concluyó que ambos anticonceptivos inyectables son muy eficaces en la regulación de la fecundidad en mujeres mexicanas aunque se señaló que es preciso controlar las alteraciones en el sangrado menstrual para que las mujeres sean más constantes en el tratamiento