Incidences of breast cancer throughout long-term hormone replacement therapy.

OBJECTIVE: To report the main incidences related to diagnosis of breast cancer in a randomly selected cohort population of women treated with conjugated equine estrogens (CEE), always in conjunction with the opposed progestin, medroxy progesterone acetate (MPA) throughout prolonged oral administration. MATERIAL AND METHODS: One hundred and seventy-eight women were subsequently studied before and during the treatment (cohort study). The profile of studied patients included family and personal histories, gynecological and breast examinations, basal hormonal levels, bone mass concentration (BMC) as well as total cholesterol levels and their fractions. The usual clinical cut off age was applied at the beginning of treatment according to following criteria: (a) women less than 60 years old (91.60%), and (b) women more than 60 years old (8.40%), by assuming that a primary protective effect of HRT might be lost or diminished after surpassing this age threshold. In all the treated women were thoroughly advised about the importance of diet, exercises and self-determination. Both oral CEE 0.625 mg/daily and either 2.5 mg/daily or 5 mg/daily of MPA were administrated in accordance with The American Fertility Society Meeting after 1995 (Seattle) recommendations, following two patterns: (1) cycles or perimenopausal women: from days 1 to 25, and (2) postmenopausal women, from Monday to Friday. No other specific treatments were prescribed. Statistical analysis was performed by using SPSS 12.0 and G-stat 2.0. RESULTS: Evaluation of basal hormonal levels, BMC, cholesterol levels and their fractions were not included in the current study. Data from the statistical analysis of 178 treated women were as follow: mean duration of treatment 8.06 years for all women; in the younger age group 7.97, and in the older age group 9.04. Total of 1405.5 woman-years of follow-up, 119 women for more than 5 years (66.85%), and more times (68.18%) with CEE plus MPA 5 mg/daily regime. Dropouts occurred in 34 women (19.10%). Main incidences: no deaths occurred during the treatment. Four cardiovascular events (2.24%) were reported. No spontaneous bone fractures were documented. Nonetheless, there were 11 bone fractures of traumatic origin (6.17%), none of them hip fractures. Four breast cancer. Likewise, one diagnosis of breast cancer in each of 45 treated women from our series was evidenced. One hundred and twenty-one women (67.97%) without incidences. COMMENTS: In our cohort study advices on diet, exercises and self-determination were reinforced for 1405.5 woman-years of follow-up. Combined CEE plus MPA for more than 5 years are no more risk related to breast cancer and cardiovascular events versus shorter treatments. Long-term CEE plus MPA were well tolerated and we did not find statistical evidence which would allow deducing higher rates of morbidity in those entities. Likewise, no deaths were document during the treatments.

Estradiol inhibits the estrone sulfatase activity in normal and cancerous human breast tissues.

It is well accepted that estradiol (E2) plays an important role in the genesis and evolution of breast cancer. Quantitative evaluation indicates that in human breast tumor, estrone sulfate (E1S) 'via sulfatase' is a much more likely precursor for E2 than is androstenedione 'via aromatase'. In previous studies, it was demonstrated that in isolated MCF-7 and T-47D breast cancer cell lines, estradiol can block estrone sulfatase activity. In the present study, the effect of E2 was explored using total normal and cancerous breast tissues. This study was carried out with post-menopausal patients with breast cancer. None of the patients had a history of endocrine, metabolic or hepatic diseases or had received treatment in the previous 2 months. Each patient received local anaesthetic (lidocaine 1%) and two regions of the mammary tissue were selected: (A) the tumoral tissue and (B) the distant zone (glandular tissue) which was considered as normal. Samples were placed in liquid nitrogen and stored at -80 degrees C until enzyme activity analysis. Breast cancer histotypes were ductal and post-menopausal stages were T2. Homogenates of tumoral or normal breast tissues (45-75 mg) were incubated in 20 mM Tris-HCl, pH 7.2 with physiological concentrations of [3H]-E1S (5 x 10(-9)M) alone or in the presence of E2 (5 x 10(-5) to 5 x 10(-7) M) during 30 min or 3 h. E1S, E1 and E2 were characterized by thin layer chromatography and quantified using the corresponding standard. The sulfatase activity is significantly more intense with the breast cancer tissue than normal tissue, since the concentration of E1 was 3.20 +/- 0.15 and 0.42 +/- 0.07 pmol/mg protein, respectively after 30 min incubation. The values were 27.8 +/- 1.8 and 3.5 +/- 0.21 pmol/mg protein, respectively after 3 h incubation. Estradiol at the concentration of 5 x 10(-7) M inhibits this conversion by 33% and 31% in cancerous and normal breast tissues, respectively and by 53% and 88% at the concentration of 5 x 10(-5) M after 30 min incubation. The values were 24% and 18% for 5 x 10(-7) M and 49% and 42% for 5 x 10(-5) M, respectively after 3h incubation. It was observed that [3H]-E1S is only converted to [3H]-E1 and not to [3H]-E2 in normal or cancerous breast tissues, which suggests a low or no 17beta-hydroxysteroid dehydrogenase (17beta-HSD) Type 1 reductive activity in these experimental conditions. In conclusion, estradiol is a strong anti-sulfatase agent in cancerous and normal breast tissues. This data can open attractive perspectives in clinical trials using this hormone.

Laparoscopic-assisted vaginal hysterectomy versus abdominal hysterectomy in stages I and II endometrial cancer. Operating data, follow up and survival.

OBJECTIVE: To assess the feasibility of laparoscopy in the treatment of early stage endometrial carcinoma and follow up outcomes compared to classic laparotomy. METHODS: A retrospective review of 90 consecutive patients with endometrial cancer managed between January 1997 and December 2003. Two groups were defined whether they had been treated by laparoscopy (N = 38; LPS group) or by laparotomy (N = 37; LPM group). Nine patients treated by vaginal hysterectomy and 6 cases with stages III-IV were excluded from the study. RESULTS: Both groups were comparable in mean age and mean BMI. Mean operating time was longer for LPS group, 164.91 +/- 5.60 (77-240) vs. 129.97 +/- 5.08 (60-180) min (P < 0.05). Intraoperative complications were seen in 7 patients (18.9%) from LPM and in 5 cases (13.2%) in the laparoscopic group. Two patients (5.2%) initially evaluated by laparoscopy were converted into laparotomy due to an increasing and uncontrollable hypercapnia. There were more post-operative complications in patients managed by laparotomy (14 cases; 38.8%), than by laparoscopy (7 cases; 18.4%) (P < 0.05). Blood transfusion was necessary in 4 patients (10.8%) in LPM group while none was required in LPS group (P < 0.01). Hospital readmission was only recorded in 3 patients treated by laparotomy (6.7%) (P < 0.05). Hospital stay was longer in LPM group 7.06 +/- 0.58 (4-21) vs. LPS 5.04 +/- 0.73 (2-17) days (P < 0.05). With a median follow up of 53.21 +/- 4.32 months for LPM (5-90) and 36.31 +/- 2.75 months for LPS (9-65) there was no significant difference in disease recurrence between the two groups. CONCLUSION: Laparoscopic staging combined with vaginal hysterectomy appears to be a feasible alternative to classical surgical approach in patients with early stage I or II endometrial carcinoma.

Bone mass, bone metabolism, gonadal status and body mass index.

Weight and gonadal status are the main determinants of bone mass in women. Because of this it is important to study which influences it more. The effect of weight (expressed as body mass index, BMI) and gonadal status of women on total-body bone mineral content (TBBMC) and regional bone mineral content (BMC) was investigated. A total of 373 normal women (mean age 48.9 +/- 13.4 years) were studied: 171 postmenopausal women (mean age 59.3 +/- 9.5 years; years since menopause 11.3 +/- 6.7 years); 76 perimenopausal women (mean age 48.9 +/- 2.2 years); and 126 premenopausal women (mean age 34.7 +/- 7.4 years). In all the women, TBBMC and regional BMC were determined by dual-energy X-ray absorptiometry. Also biochemical markers of bone metabolism (total alkaline phosphatase and tartrate-resistant acid phosphatase) and serum estrone and estradiol were determined. When the women were stratified by gonadal status and BMI, thin women (BMI <20 kg/m2) had significantly lower TBBMC and regional BMC, lower gonadal steroid concentration and higher levels of biochemical markers than overweight (BMI 25-30 kg/m2) and obese (BMI >30 kg/m2) women, regardless of gonadal status. Overweight and obese women had findings suggestive of increased parathyroid activity, but greater bone mass. Weight rather than gonadal steroid concentration is the main determinant of bone mass in women regardless of gonadal status.

Can a determination of tartrate-resistant acid phosphatase predict postmenopausal loss of bone mass?

BACKGROUND: A study was carried out over a 24-month interval to determine if an initial measurement of serum tartrate-resistant acid phosphatase would be predictive of bone mass loss quantified by dual-energy X-ray absorptiometry, as total bone mineral content and total bone mineral content corrected for weight. DESIGN: Sixty-two women were studied (at onset: mean age 59.7 +/- 8.9 years, 10.8 +/- 8.8 years since menopause; at conclusion: mean age 61.9 +/- 8.8 and 13.0 +/- 8.7 since menopause). RESULTS: A paired Wilcoxon test showed a small, but significant, increase in weight (P < 0.05) and decrease in height (P < 0.05). Total bone mineral content and total bone mineral content corrected for weight decreased (P < 0.005 and 0.0001, respectively). Serum tartrate-resistant acid phosphatase increased (P < 0.005). Single-regression analysis showed that the per cent bone mass loss observed between the first and second body bone mineral content measurements correlated negatively with the first serum tartrate-resistant acid phosphatase determination (r = -0.62, P < 0.0001). Changes in tartrate-resistant acid phosphatase correlated negatively with changes in total bone mineral content (r = -0.79, P < 0.0001). In a multiple regression analysis of per cent change in bone mass against initially important variables such as age, years since menopause, weight, and tartrate-resistant acid phosphatase, only tartrate-resistant acid phosphatase was significant (P < 0.0001). The sensitivity and specifity of tartrate-resistant acid phosphatase for evaluating bone loss were 86% and 78%, respectively, and the area under the curve was of 0.83 (95% CI 0.71-0.95). CONCLUSION: These results show that a simple measurement of serum tartrate-resistant acid phosphatase can help to predict the potential rate of bone mass loss in women.

El cáncer de endometrio en la década de los 90. Análisis de 126 casos / Endometrial cancer in the 90s. Analysis of 126 cases

Propósito: Analizar la casuística y la evolución del cáncer de endometrio en nuestra Área Sanitaria durante la década de los años 90.• Material y métodos: Se trata de un trabajo retrospectivo. Se revisaron 126 casos de cáncer de endometrio diagnosticados entre enero de 1990 y diciembre 1999 en el Hospital Universitario Príncipe de Asturias de Alcalá de Henares. Se utilizó la clasificación anatomo-clínica FIGO-2000.• Resultados: La edad media fue de 60.3 ñ 11.5 años. La histeroscopia y biopsia de endometrio fue el método diagnóstico mas frecuente (89 por ciento), sobre todo a partir del año 1994. En el 97.6 por ciento de los casos se realizó cirugía, recibieron radioterapia el 33 por ciento con un tiempo medio de seguimiento de 56 ñ 20 meses (1-100). La mayoría de los tumores eran diagnosticados en estadio I (74 por ciento). Histológicamente, el 93 por ciento correspondían al tipo endometrioide. Un 13 por ciento de las pacientes presentaban tumores coincidentes, especialmente cáncer de mama. La remisión completa tras el tratamiento inicial se ha obtenido en el 93.6 por ciento de los casos con unas tasas de supervivencia a los 10 años del 79 por ciento.• Conclusiones: La histeroscopia con biopsia de endometrio se ha impuesto como técnica diagnóstica en esta década. La cirugía se mantiene como tratamiento primario primordial, y las tasas de supervivencia, en la actualidad, son elevadas. (AU)

Metástasis intraabdominales de un carcinoma lobulillar infiltrante de mama. A propósito de un caso clínico y revisión del tema / Intraabdominal metastases from infiltrating lobular carcinoma of the breast

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[Cortical bone mass and risk factors for osteoporosis among postmenopausal women in our environment]. / Masa ósea cortical y factores de riesgo para osteoporosis en mujeres postmenopáusicas en nuestro medio.

OBJECTIVE: To evaluate the relevance of the so called risk factors for osteoporosis among women. MATERIALS AND METHODS: A total of 150 consecutive postmenopausal women who had been enrolled in the gynecology outpatient clinics of the Health Areas affiliated to the Alcalá de Henares University Hospital. Bone mass of these women was calculated as index of metacarpal cortical area/total area (CA/TA) (mm2), measured by radiogrammetry. RESULTS: With the ANOVA test, a late menarchial age and a shorter reproductive life induced a lower bone mass (p < 0.0005 and < 0.05, respectively); also, a history of bone fractures without previous relevant trauma (p < 0.05) was obtained. By correlational studies, there was a negative significance between CA/TA index and chronological age, menarchial age, menopausal age and number of fractures (r = -0.20 to -0.30; p < 0.05 to < 0.0001) and a positive significance with years of reproductive life (r = 0.17; p < 0.05). These values virtually remain unchanged when with partial correlation are weight adjusted, but with the multiple regression model, the CA/TA index is negatively significant only with menopause years (p < 0.005). Taking the average of the metacarpal CA/TA index as value, a sensitivity of 50% and an specificity of 78% were obtained to indicate fractures and a negative predictive value of 92%. CONCLUSION: These results indicate the greater importance of menarchial age, of reproductive life years and therefore of menopausal years, as determinants of postmenopausal bone mass and show a very acceptable specificity of the CA/TA index as predictive for bone fracture.

Miomectomía histeroscópica. Valoración del tratamiento previo con agonistas LH-RH / Hysteroscopic myomectomy. Evaluation of prior treatment with LH-RH agonists

Objetivo: Estudio prospectivo de 61 miomectomías histeroscópicas para valorar la utilidad del tratamiento previo con agonistas de la hormona liberadora de hormona luteinizante (LHRH).Material y métodos: Se realizaron 61 miomectomías en 50 pacientes entre enero de 1995 y diciembre de 1998. Se seleccionaron 2 grupos homogéneos según recibieran o no tratamiento previo con análogos, repartiendo la administración de la medicación en años alternos. Se desarrolló un protocolo de seguimiento en la consulta de ginecología.Resultados: El número medio ñ desviaciones estándar de miomas encontrados fue de 1,12 ñ 0,07, con un tamaño medio de 26,16 ñ 14,9 mm y en su mayor número 27 (54 por ciento) tipo I (Wamsteker).En 46 pacientes (92 por ciento) el tratamiento fue exitoso, en cuatro (8 por ciento) fracasó, en tres de los cuales realmente existió una mala indicación de la técnica (útero polimiomatoso). No hubo complicaciones intraoperatorias. Hubo una complicación postoperatoria (infección urinaria). Días de ingreso postoperatorio: 1.En el estudio comparativo no existieron diferencias significativas tanto en los datos técnicos como en la mejoría de la sintomatología clínica entre el grupo de pacientes tratados y el de no tratados con agonistas LHRH.Conclusión: La miomectomía por histeroscopia quirúrgica es un buen método de tratamiento con una alta tasa de curación y una escasa morbilidad.El uso del tratamiento previo y rutinario con análogos LHRH en esta cirugía, en nuestra casuística no aportó beneficios significativos ni mejoría en los resultados clínicos obtenidos y, por contra, incrementó el coste por proceso, aunque esto no llegaría a excluir su uso selectivo e individualizado en ciertos casos. (AU)

Masa ósea cortical y factores de riesgo para osteoporosis en mujeres postmenopáusicas en nuestro medio / Cortical bone mass and risk factors for osteoporosis among postmenopausal women in our environment

Objetivo. Valorar la importancia de los denominados factores de riesgo para la osteoporosis en las mujeres. Material y métodos. Se estudian 150 mujeres postmenopáusicas, seleccionadas de forma consecutiva en las consultas ambulatorias de ginecología del área de salud del Hospital Universitario de Alcalá de Henares, cuya masa ósea se calcula como índice área cortical/área total (AC/AT) metacarpiana (mm2) determinada por radiogrametría. Resultados. Por el análisis de varianza ANOVA se determina que una menarquía tardía y una vida reproductiva más corta inducen una menor masa ósea (p < 0,0005 y < 0,05, respectivamente) y también el antecedente de fracturas óseas sin trauma importante previo (p < 0,05). Por estudios de correlación hay una significación negativa entre el índice AC/AT y la edad cronológica, la de la menarquía, la de la menopausia y el número de fracturas (r = -0,20 a -0,30, p < 0,05 a < 0,0001) y positiva con los años de vida reproductiva (r = 0,17, p < 0,05). Estos valores prácticamente no cambian cuando con correlación parcial se ajustan al peso, pero al hacer una regresión múltiple el índice AC/AT es únicamente significativo de forma negativa con los años de menopausia (p < 0,005). Tomando como valor el medio del índice AC/AT metacarpiana del grupo de mujeres con antecedente con fracturas se observa una sensibilidad del 50 por ciento y una especificidad del 78 por ciento para indicar fracturas y un valor predictivo negativo el 92 por ciento. Conclusión. Estos resultados señalan la mayor importancia de la edad de la menarquía, de los años de vida reproductiva y, por ende, de los años de menopausia como determinantes de la masa ósea postmenopáusica y demuestran de muy aceptable especificidad del índice AC/AT como predictivo de fractura ósea (AU)

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Gynecological factors and body mass index as determinants of bone mass in normal postmenopausal women. A study with peripheral quantitative computed tomography (pQCT).

OBJECTIVE: This paper studied the influence of several gynecological factors (years since menopause (YSM), age at menarche and gynecological age or reproductive life) simultaneously with anthropometric factors as determinants of bone mass in 189 healthy postmenopausal women. METHODS: Bone mass was determined by peripheral quantitative computed tomography. RESULTS: An overall evaluation showed that YSM correlated negatively with trabecular and cortical bone density (BMDTrab and BMDCorti) (P<0.05 in both cases). Age at menarche correlated negatively with BMDCorti (P<0.05) and gynecological age correlated positively with BMDTrab (P<0.05). Classifying the women according to their body mass index (BMI), the YSM correlation persisted in those subjects whose BMI was >25 kg/m(2), and in age at menarche and gynecological age of women whose BMI was <25 kg/m(2) (P<0.05). After separating women according to their age at menarche, their gynecological age and BMI, the only significant difference that persisted was in BMDTrab which was lower in the group with gynecological age <33 years, with a BMI <25 kg/m(2) (P=0.020). Parity and smoking had no impact on our results. By multiple regression, with BMD as the dependent variable and the gynecological factors as independent variables, we only observed significance between YSM and BMDCorti (P<0.005). The same was observed after separating women according to their BMI in the >25 kg/m(2) group (P<0.05). CONCLUSIONS: Our data stress the importance of YSM on BMDTrab and BMDCorti, of age at menarche on BMDCorti and of gynecological age on BMDTrab. However, YSM is the gynecological factor that mainly determines BMD. The differences observed between measurements taken with pQCT and other methods commonly used to estimate bone mass indicate that results obtained with one technique cannot be extrapolated to other methods.

Hallazgos histeroscópicos en la hemorragia uterina anormal con biopsia a ciegas previa negativa / Hysteroscopic findings in abnormal uterine bleeding with a previous negative blind biopsy

Estudiamos una muestra de 408 pacientes, en un estudio retrospectivo, tratando de evaluar la fiabilidad del estudio biópsico a ciegas para el diagnóstico de la patología endometrial. Se realiza histeroscopia diagnóstica en aquellas pacientes que presentan algún tipo de hemorragia uterina anormal (HUA). Premenopáusicas (267); posmenopáusicas (141); cíclicas (305); acíclicas (103), y que previamente han sido estudiadas con una biopsia endometrial con resultado negativo (legrado en posmenopáusicas y en hemorragias cíclicas y biopsia endometrial [Z-sampler] en premenopáusicas). Realizamos estudio estadístico con pruebas de la X2 mediante análisis informático SPSS. La biopsia endometrial presenta un alto índice de falsos negativos; no diagnosticando, en este estudio, hasta un 37,2 por ciento de patología orgánica en premenopáusicas y un 43,8 por ciento en posmenopáusicas, fundamentalmente a expensas de pólipos y miomas e incluso adenocarcinomas de endometrio (1,4 por ciento). Los hallazgos histeroscópicos no fueron condicionados por el tipo de hemorragia ni por la condición premenopáusica o posmenopáusica. La histeroscopia debe ser considerada el método diagnóstico de elección en el estudio de la hemorragia uterina anormal, y debe combinarse siempre con el diagnóstico anatomopatológico (AU)

Comparison of estrogen concentrations, estrone sulfatase and aromatase activities in normal, and in cancerous, human breast tissues.

In the present study, the concentrations of estrone (E(1)), estradiol (E(2)) and their sulfates (E(1)S and E(2)S), as well as the sulfatase and aromatase activities, were evaluated in post-menopausal patients with breast cancer. Comparative studies of the evaluation of these parameters were carried out in (a) tumor tissue, (b) areas surrounding the tumor, and (c) areas distant from the tumor (glandular tissue) which were considered as normal tissue. The levels (in pm/g; mean +/- SEM) were: for E(1) in the (a) area: 320+/-95; in (b): 232+/-86; and in (c): 203+/-71; for E(2) in the (a) area: 388+/-106; in (b): 224+/-48; and in (c): 172+/-80; for E(1)S in the (a) area: 454+/-110; in (b): 259+/-90; and in (c): 237+/-65; for E(2)S in the (a) area:318+/-67; in (b): 261+/-72; and in (c): 232+/-75, respectively. The values of E(1)S and E(2) were significantly higher in the tumor tissue than in the area considered as normal. In all the tissues studied, the sulfatase activity was much higher than aromatase (130-200). In addition, the sulfatase levels were significantly higher in the peripheral and in the tumor tissue than in the area considered as normal. The levels of aromatase were significantly higher in tumoral than in normal tissue. The present data extend the "intracrine concept" for breast cancer tumors. The physiopathology and clinical significance as promoter parameters in breast cancer is to be explored.

Ultrasonographic bone velocity in pregnancy: a longitudinal study.

OBJECTIVE: Longitudinal changes in bone mass were evaluated with use of ultrasonography and bone remodeling markers in 40 normal pregnant women in relation to their calcium intake. STUDY DESIGN: The study took place at the University of Alcalá Hospital in Madrid. Biochemical markers of bone remodeling and ultrasonographic bone propagation velocity in the proximal phalanxes of fingers 2 to 5 were measured in all three trimesters of pregnancy. Wilcoxon, unpaired and paired t tests, and analysis of variance were used. RESULTS: Ultrasonographic bone propagation velocity (meters per second) was lower in the second and third trimesters of pregnancy (p < 0.0001) compared with the respective preceding trimesters and in the third trimester in the overall group of pregnant women. Tartrate-resistant acid phosphatase and alkaline phosphatase levels increased significantly (p < 0.0001) in parallel with the ultrasonographic bone propagation velocity decrease. CONCLUSIONS: Gestation was accompanied by a reduction in ultrasonographic bone propagation velocity that was greater in women with low calcium intake.

Concentrations of estrone, estradiol and their sulfates, and evaluation of sulfatase and aromatase activities in patients with breast fibroadenoma.

In the present studies, the concentrations (mammary tissue and plasma) of estrone (E1), estradiol (E2) and their sulfates (E1S and E2S), as well as the sulfatase and aromatase activities, were evaluated in patients with breast fibroadenomas. Comparative studies of the evaluation of these parameters were carried out in: (A) tumor tissue, (B) areas surrounding the tumor and (C) areas distant from the tumor (glandular tissue) considered as normal tissue. The concentrations in the tumor tissue (in pmol/g tissue) of E1, E2 and E1S were significantly higher (2-3 times) than in the area of the breast considered as normal. Sulfatase and aromatase activities were found in the breast fibroadenoma tissue. Sulfatase activity was much higher than aromatase (30-150 times) and sulfatase levels were significantly higher in the fibroadenoma tissue than in the area considered as normal. Plasma evaluation of E1, E2, E1S and E2S concentrations showed no significant differences in relation to those of healthy control women. In conclusion, the high levels of estrogens and their sulfates, as well as the enzymes involved in estrogen formation--sulfatase and aromatase in breast fibroadenoma--contribute to the hypothesis that this disease may be hormone-dependent.

Evaluation of gestrinone after surgery in treatment of endometriosis.

OBJECTIVE: The clinical and histological efficacy of gestrinone in the treatment of endometriosis was evaluated. METHODS: A prospective study was performed with longitudinal follow-up of 4 years duration (minimum) for each patient. Twenty-five cases of endometriosis were treated with gestrinone (as a drug of choice or associated with other local surgical treatment) during 6 months. RESULTS: The total or partial response to pain was induced with treatment in 19 of the 20 cases (95%), and posttreatment pregnancies were induced in 3 of the 9 cases of infertility (33.3%). The global clinical efficacy was as follows: none (n = 5, 20%), poor (n = 2, 8%), moderate (n = 2, 8%), good (n = 3, 12%) and excellent (n = 13, 52%). The pretreatment American Fertility Society score was 23.1 +/- 3.8 points (2-58) and that after treatment (re-examination) 7.8 +/- 3.7 points (0-52), p < 0.01. Global histological efficacy (n = 17) results were as follows: none (23.6%), poor (0%), moderate (5.8%), good (35.3%) and excellent (35.3%). CONCLUSIONS: Gestrinone is presented as a drug with an efficacy comparable to other pharmacological agents currently available in the medical treatment of endometriosis. Adequate posology and acceptable effectiveness were also observed.

Long-term follow-up of endometriosis after two different therapies (Gestrinone and Buserelin).

OBJECTIVE: To compare the efficacy, tolerance and recurrence rate of endometriosis after 5-year follow-up of treatment with Gestrinone and Buserelin, respectively. STUDY DESIGN: A prospective study with randomized follow-up of 5 years duration (minimum) for each patient was done. We included 43 cases of endometriosis diagnosed by laparoscopy or laparotomy and treated them with Gestrinone (Group G, n = 25 cases) or Buserelin intranasal spray (Group B, n = 18) for 6 months. RESULTS: General data: Age, height, weight of patients and AFS score of endometriosis were without significant differences in either group. Specific data: A) Global clinical efficacy was good or excellent in 74% (16/25) of group G and in 78% (14/18) of group B without significant differences. B) Global clinical tolerance was good in 50% of the patients in group G and in 0% in group B (p < 0.001). C) Global evaluation after 5-year follow-up showed "success" only for 36% of patients in group G and in 33% in group B (no significant differences), with "failure" in 40% and 33%, respectively (no significant differences). CONCLUSIONS: 1) Gestrinone and Buserelin intranasal spray are valid treatments for the remission of endometriosis, with "success", "failure" and "clinical recurrence" rates similar after a follow-up of 5 years of initial treatment. 2) The most significant androgenic effect of Gestrinone was the presence of acne. Vascular effects were also considered as very undesirable effects according to the comments of patients. On the contrary, the effects of analogs are generally better tolerated.

HLA class I, class II, and class III antigen sharing is not found in couples with unexplained infertility.

OBJECTIVE: To find the degree of HLA antigen sharing in couples with infertility of unknown etiology and compare it with that in couples with infertility of known etiology as well as couples with normal fertility. SUBJECTS: Eleven couples with infertility of unknown etiology, 26 with infertility of known etiology, and 31 fertile couples were tested for HLA class I (A, B, C), class II (DR, MLC), and class III (Bf) antigens and GLO alleles. HLA lymphocytotoxic antibodies and anti-sperm antibodies in both partners were also searched. RESULTS: Gene frequencies and the number of HLA antigens shared between the two members of the couple were similar in all groups. When "intra-couple" MLC reactivity was measured, no quantitative differences were found in the infertile group with unknown etiology, as compared to the group of known etiology: spouses in couples of either group usually reacted in both ways as expected for unrelated individuals" lymphocytes. Lymphocytotoxic antibody frequency did not differ between the nonfertile groups, and anti-sperm antibodies, found in ten patients in the group of known etiology, were not associated with any HLA antigen. In spite of that, GLO and all the HLA antigen classes described (I, II and III) were analyzed. CONCLUSIONS: Although the results are negative, these and others' (negative) results concerning couples with infertility of unknown etiology do not disprove that HLA has a role in fertilization, because HLA-related factors still unknown may exist. Exhaustive HLA available marker typing in international cooperative efforts may be needed to reach a significant number of carefully selected couples fully HLA typed to elucidate this problem.

Long-acting agonists of LH-RH in the treatment of large ovarian endometriomas.

Reversible temporary medical oophorectomy using long-acting agonist analogs of LH-RH was tried in three infertile patients suffering from large endometriomas of the ovary. These patients had stage IV disease according to the revised 1985 classification of the American Fertility Society. D-Ala6-des-Gly10-LH-RH propylamide (D-Ala6-LH-RH PA), in a dose of 125 micrograms, was administered intramuscularly every 48 hours to one patient, and daily to the other two patients, for 22, 17, and 14 weeks, respectively. Two patients subsequently received 100 micrograms of D-Trp6-LH-RH for 4 weeks in order to compare its efficacy with D-Ala6-LH-RH PA. Clinical controls, pelvic ultrasonography, and routine laboratory tests and hormone assays were done periodically. Ultrasonography images showed a reduction in the size of endometriomas after the second or third week of treatment. This reduction was maintained throughout and continued after the period of treatment. Suppression of the pituitary and estrogen responses was obtained rapidly, but some transient increments were occasionally found. Progesterone levels always decreased and remained in the range of the early follicular phase. Most intervals of uterine bleeding were prolonged. An evident improvement of abdominal pain, dysmenorrhea, and dyspareunia was found. Administration of D-Trp6-LH-RH was more effective than D-Ala6-LH-RH PA in most of the parameters tested. After discontinuation of treatment, all three patients had a prolonged follicular phase with a normal luteal phase during the first cycle. One woman became pregnant in the fourth cycle after discontinuation of D-Ala6-LH-RH PA and delivered a normal baby.(ABSTRACT TRUNCATED AT 250 WORDS)

Coagulation and fibrinolysis in post-menopausal women treated with Org OD 14.

The effects of a new synthetic steroid Org OD 14 on the haemostatic mechanism were investigated in 60 post-menopausal women, randomly allocated to 12 weeks of treatment with either 2.5 mg/day of Org OD 14 or a placebo in a double-blind, group-comparative study. Assessments were made 2 weeks before and just prior to the start of treatment, at weeks 6 and 12 during treatment, and 2 weeks after its cessation. No significant differences between the two groups were found with regard to prothrombin time, kaolin cephalin clotting time (KCCT), clotting factors VII, VIII and X, white blood count (WBC) or transaminases (ASAT, ALAT). The following statistically significant differences were seen in the Org OD 14 group: higher plasminogen, antithrombin III, haemoglobin, haematocrit and platelet count, and increased fibrinolytic activity on fibrin plates, as well as lower fibrinogen and alkaline phosphatase values. These findings indicate that Org OD 14 displays no adverse effects on coagulation, while changes in fibrinolysis seem to be beneficial for post-menopausal women.