Quantum dynamics of the intramolecular vibrational energy redistribution in OCS: From localization to quasi-thermalization.

We report a fully quantum-dynamical study of the intramolecular vibrational energy redistribution (IVR) in the electronic ground state of carbonyl sulfide, which is a prototype of an isolated many-body quantum system with strong internal couplings and non-Rice-Ramsperger-Kassel-Marcus (RRKM) behavior. We pay particular attention to the role of many-body localization and the approach to thermalization, which currently are topics of considerable interest, as they pertain to the very foundations of statistical mechanics and thermodynamics. We employ local-mode (valence) coordinates and consider initial excitations localized in one local mode, with energies ranging from low to near the dissociation threshold, where the classical dynamics have been shown to be chaotic. We propagate the nuclear wavepacket on the potential energy surface by means of the numerically exact multiconfiguration time-dependent Hartree method and employ mean local energies, time-dependent and time-averaged populations in quantum number space, energy distributions, entanglement entropies, local population distributions, microcanonical averages, and dissociation probabilities, as diagnostic tools. This allows us to identify a continuous localization → delocalization transition in the energy flow, associated with the onset of quantum chaos, as the excitation energy increases up to near the dissociation threshold. Moreover, we find that at this energy and ∼1 ps the molecule nearly thermalizes. Furthermore, we observe that IVR is so slow that the molecule begins to dissociate well before such quasi-thermalization is complete, in accordance with earlier classical-mechanical predictions of non-RRKM behavior.

[Periprosthetic hip fractures]. / Fracturas periprotésicas de cadera.

UNLABELLED: The incidence rate of periprosthetic fractures has increased in the past decade. Osteolysis, age and preoperative function are factors that influence morbidity. Treatment options include conservative and surgical treatment. OBJECTIVES: To conduct a study analyzing the functional results of the surgical treatment of periprosthetic hip fractures at the ABC Medical Center considering preoperative and postoperative variables. MATERIAL AND METHODS: Cross-sectional retrospective study of patients with a diagnosis of periprosthetic hip fracture between January 2000 and December 2011, classified using the Vancouver system. The Oxford Hip Score was used pre- and postoperatively as a functional measure. The variables to evaluate included age, sex, surgical technique, and the time elapsed between primary surgery and the periprosthetic fracture. RESULTS: Twenty-five patients were analyzed; frequency was 3.3 cases per year. 80% of periprosthetic fractures were postoperative; 72% were total hip arthroplasties. The time elapsed between primary surgery and the traumatic event was 2 to 4 years (68%), with a mean of 4.5 years for hemiarthroplasties and 3.9 years for total arthroplasties. Patients who according to the Oxford Hip Score had good function maintained their results; 75% of those with moderate function maintained their score. Patients with poor function improved. CONCLUSIONS: At the ABC Medical Center, the outcomes of the treatment of periprosthetic hip fractures are considered as good according to the Oxford Hip Score.

Envelope molecular-orbital theory of extended systems. I. Electronic states of organic quasilinear nanoheterostructures.

A conceptually appealing and computationally economical course-grained molecular-orbital (MO) theory for extended quasilinear molecular heterostructures is presented. The formalism, which is based on a straightforward adaptation, by including explicitly the vacuum, of the envelope-function approximation widely employed in solid-state physics leads to a mapping of the three-dimensional single-particle eigenvalue equations into simple one-dimensional hole and electron Schrödinger-like equations with piecewise-constant effective potentials and masses. The eigenfunctions of these equations are envelope MO's in which the short-wavelength oscillations present in the full MO's, associated with the atomistic details of the molecular potential, are smoothed out automatically. The approach is illustrated by calculating the envelope MO's of high-lying occupied and low-lying virtual π states in prototypical nanometric heterostructures constituted by oligomers of polyacetylene and polydiacetylene. Comparison with atomistic electronic-structure calculations reveals that the envelope-MO energies agree very well with the energies of the π MO's and that the envelope MO's describe precisely the long-wavelength variations of the π MO's. This envelope MO theory, which is generalizable to extended systems of any dimensionality, is seen to provide a useful tool for the qualitative interpretation and quantitative prediction of the single-particle quantum states in mesoscopic molecular structures and the design of nanometric molecular devices with tailored energy levels and wavefunctions.

Mid-luteal progesterone concentrations are associated with live birth rates during ovulation induction.

This retrospective study investigated whether mid-luteal serum progesterone concentrations are associated with live birth rates in women with WHO group II anovulatory infertility undergoing ovulation induction. Data were from women (n=335) stimulated with gonadotrophins using a low-dose step-up protocol, of which women with presumptive ovulation (n=279), defined as a mid-luteal progesterone concentration ⩾7.9ng/ml (⩾25nmol/l; range 7.9-194ng/ml) were included. Of the women with presumptive ovulation, 57 (20.4%) had a live birth and their serum mid-luteal progesterone concentration was significantly (P=0.016) higher than that of the non-live birth group. There were significant associations between the number of large (⩾15mm) and medium-sized follicles (12-14mm) at human chorionic gonadotrophin administration and the mid-luteal progesterone concentration (P<0.001), while the total number of large and medium-sized follicles was not significantly associated with live birth rate. In conclusion, mid-luteal progesterone concentrations above the cut-off values currently used for defining ovulation were positively associated with live birth rates in normogonadotrophic anovulatory women undergoing ovulation induction with gonadotrophins. The mid-luteal progesterone concentration, apart from being a consequence of the number of corpora lutea, may also reflect the quality of the follicle/oocyte/corpus luteum. Measurement of blood concentration of the steroid hormone progesterone in the mid-postovulatory phase of the menstrual cycle is frequently used to determine ovulation. The aim of this study was to investigate whether increasing blood concentrations of progesterone in the mid-postovulatory phase was associated with higher chances of achieving a live birth in a group of 335 women with anovulatory infertility, who had undergone stimulation with gonadotrophin hormones for the purpose of inducing ovulation. Statistical analysis, performed on the 279 women with presumptive ovulation (defined as a mid-postovulatory progesterone concentration ⩾7.9ng/ml serum), showed that the mid-postovulatory progesterone concentration was significantly positively associated with live birth rate. There was also a significant association between follicular development at end of gonadotrophin stimulation and the mid-postovulatory progesterone concentration, but follicular development could not explain live birth rate as mid-postovulatory progesterone concentrations could. In conclusion, increased blood concentrations of progesterone in the mid-postovulatory phase of the menstrual cycle above the threshold values currently used for defining ovulation were associated with increased live birth rates in anovulatory women undergoing ovulation induction with gonadotrophin hormones. The mid-postovulatory progesterone concentration, apart from being a consequence of the quantity of follicular development, may therefore also reflect the quality of the ovarian follicles and eggs.

Prestimulation parameters predicting live birth in anovulatory WHO Group II patients undergoing ovulation induction with gonadotrophins.

BACKGROUND: The objective of this study was to identify baseline predictors of live birth in anovulatory patients undergoing ovulation induction, and based on these predictors, develop nomograms for estimation of the probability of live birth in a single cycle. METHODS: Univariate and multivariate logistic regression were used for retrospective analysis of clinical, sonographic and endocrinological parameters collected prior to the start of ovarian stimulation in a cohort of anovulatory World Health Organization (WHO) Group II patients (n = 335), who were resistant to clomiphene citrate (CC) and therefore stimulated with gonadotrophins using a low-dose step-up protocol. RESULTS: The univariate analysis identified age [OR = 0.91 (95% CI: 0.84-0.98), P = 0.015], duration of infertility [OR = 0.71 (95% CI: 0.56-0.91), P = 0.007], serum follicle stimulating hormone (FSH) concentration at the start of stimulation [OR = 0.83 (95% CI: 0.69-0.99), P = 0.034] and menstrual cycle pattern (P = 0.022) as significant predictors of live birth. Baseline concentrations of luteinizing hormone, androgens, glucose and insulin, as well as body mass index, were not predictors of live birth. In the multivariate analysis, duration of infertility, FSH and menstrual cycle pattern were independent predictors, and nomograms were designed with these three parameters for individual prediction of the probability of live birth. CONCLUSIONS: The chances of live birth in women with WHO Group II anovulatory infertility resistant to CC undergoing ovulation induction with gonadotrophins is highly influenced by the menstrual cycle pattern. Increases in duration of infertility and concentration of FSH (within the normal range) before the start of stimulation have negative influences on the likelihood of achieving a live birth.

Manipulating and imaging the shape of an electronic wave function by magnetotunneling spectroscopy.

We measure the current due to electrons tunneling through the ground state of hydrogenic Si donors placed in a GaAs quantum well in the presence of a magnetic field tilted at an angle to the plane of the well. The component of B parallel to the direction of current compresses the donor wave function. By measuring the current as a function of the perpendicular component of B, we probe how the magnetocompression affects the spatial form of the wave function and observe directly the transition from Coulombic to magnetic confinement at high fields.

Endocrine profile in serum and follicular fluid differs after ovarian stimulation with HP-hMG or recombinant FSH in IVF patients.

BACKGROUND: Highly purified menotrophin (HP-hMG) has been associated with fewer oocytes retrieved and a higher proportion of top-quality embryos compared with recombinant FSH (rFSH). METHODS: A randomized, assessor-blind, multinational trial in 731 women undergoing IVF after stimulation with HP-hMG (MENOPUR) (n = 363) or rFSH (GONAL-F) (n = 368) following a long GnRH agonist protocol was conducted. Blood was collected before, during and after stimulation. Fluid was collected from follicles > or =17 mm. RESULTS: Serum androstenedione, total testosterone and free androgen index (FAI) were higher (P < 0.001) with HP-hMG than with rFSH after starting stimulation. At the end of stimulation, serum estradiol was higher (P = 0.031) with HP-hMG, whereas progesterone was higher (P < 0.001) with rFSH, even after adjusting for ovarian response. Serum LH was not different between treatments. Mean mid- and end-follicular hCG levels in the HP-hMG group were 2.5 and 2.9 IU/l, respectively. Follicular fluid levels of FSH, LH, hCG, androstenedione, testosterone, FAI and estradiol and ratios of estradiol:androstenedione, estradiol:total testosterone and estradiol:progesterone were higher (P < 0.001) with HP-hMG, whereas progesterone was higher (P < 0.001) with rFSH. CONCLUSION: Major differences in serum and follicular fluid endocrine profile exist after stimulation with HP-hMG or rFSH. Exogenous LH activity induces a differential endocrine environment influencing oocyte quantity and quality, which may be of relevance for clinical outcome.

The influence of body weight on response to ovulation induction with gonadotrophins in 335 women with World Health Organization group II anovulatory infertility.

OBJECTIVE: To assess the influence of body weight on the outcome of ovulation induction in women with World Health Organization (WHO) group II anovulatory infertility. DESIGN: The combined results of two studies in which either a highly purified urinary follicle-stimulating hormone or highly purified urinary menotrophin were compared with recombinant follicle-stimulating hormone. SETTING: Thirty-six fertility clinics. POPULATION: A total of 335 women with WHO group II anovulatory infertility failing to ovulate or conceive on clomifene citrate. METHODS: Ovarian stimulation using a low-dose step-up protocol. MAIN OUTCOME MEASURES: The effects of body weight on ovarian response, ovulation rate and pregnancy rate after one treatment cycle. RESULTS: With increasing body mass index (BMI), a higher threshold dose of gonadotrophins was required and there were more days of stimulation; yet, despite a greater concentration of antral follicles, there were fewer intermediate and large follicles. There was no difference in the rates of ovulation and clinical pregnancy in relation to body weight. CONCLUSIONS: Body weight affects gonadotrophin requirements but not overall outcome of ovulation induction in women with anovulatory polycystic ovary syndrome and a BMI of less than 35 kg/m2.

Prescripción del ejercicio físico y salud ósea / Prescription of the physical exercise and bone health

La osteoporosis es un problema sanitario de gran importancia a nivel mundial, así reconocido por la OMS. Concretamente, en nuestro medio, más del 40% de las mujeres y el 10% de los hombres mayores de 60 años presentan, disminución de la densidad de su masa ósea (DMO). En el presente trabajo revisamos la mayoría de los artículos publicados en los últimos 30 años que relacionan el ejercicio físico con la DMO, la osteoporosis y el riesgo de fractura debido a la misma. Basándonos en la revisión realizada, proponemos un plan de ejercicio físico (guías de prescripción de ejercicios según DMO), que puede ser aplicado en la prevención y el tratamiento de la osteoporosis, con objeto de minimizar el riesgo de fractura. El ejercicio físico, que ha demostrado efectos concretos sobre la DMO, puede ser un factor muy positivo en el manejo de estos pacientes

Osteoporosis is a health problem of high importance all over the world, recognised by the WHO. More than 40% of the women and 10% of the men over 60 in our society suffer from a significant loss of their osseous mass density (OMD). In this research, we have reviewed most of the articles that have been published during the last 30 years and in which a relationship between physical exercise, OMD, osteoporosis and fracture risks has been found. According to the results of our review, we propose a physical exercise program (exercise prescription guide according to the OMD), that can be applied to osteoporosis prevention and treatment in order to minimize fracture risks. Physical exercise has certain effects on the OMD which have been proved and it can play a very important role as part of the treatment for patients who suffer from osteoporosis

Resolving methodological and clinical issues in the design of efficacy trials in assisted reproductive technologies: a mini-review.

The validity, importance and relevance of randomized controlled trials depend on identifying an appropriate target population, ensuring adequate power, careful attention to the details of randomization and blinding, and selection of an endpoint that is important to the target population. With efficacy trials more than effectiveness trials, additional constraints are needed to reduce the variability that is typical of clinical practice: a narrowly defined sample, unvarying pre-randomization procedures and post-randomization treatments and follow-up that are as identical as possible for all patients. Efficacy trials comparing ovarian stimulation protocols should have strict protocol definitions, specific concomitant medications and minimal variability between centres with respect to stimulation goals and dose adjustments. Additionally, there should be narrowly defined criteria for administration of chorionic gonadotrophin, type of luteal support, embryo transfer and freezing policies. The goal of efficacy trials is to minimize the variability that is extrinsic to the comparison. When efficacy has been proven, effectiveness trials are needed to determine whether the effect of the new intervention is robust in the variability of typical clinical settings.

Chromosomal abnormality rate in human pre-embryos derived from in vitro fertilization cycles cultured in the presence of Follicular-Fluid Meiosis Activating Sterol (FF-MAS).

BACKGROUND: The objective of the study was to investigate the effect of Follicular-Fluid Meiosis Activating Sterol (FF-MAS) when added to the culture media on the incidence of chromosomal abnormalities and pre-embryo development in human pre-embryos. METHODS: 243 women undergoing IVF/ICSI treatment donated 353 oocytes in a multicentre, prospective, randomized, double blind, four-arm, controlled trial performed at Danish and Swedish public and private IVF centers. Metaphase II oocytes were randomly assigned to: FF-MAS 5 microM, FF-MAS 20 microM, ethanol 0.2% (vehicle control) or water for injection (inert control). The exposure regimen of FF-MAS to the human oocytes was 4 h prior to fertilization by ICSI and 20 h exposure post ICSI. The primary endpoint was the incidence of numerical chromosomal abnormalities. Secondary endpoints were cleavage rate and pre-embryo quality. RESULT: On the pre-embryo level, no significant differences in chromosomal abnormality rate were observed among the four groups. However, the percentage of uniformly normal pre-embryos was significantly lower in the pooled FF-MAS group (5 microM: 12% and 20 microM: 17%) than in the pooled control group (inert control 32% and vehicle control 42%). A high level of mosaicism (41-60%) was found in all groups. At the blastomere level, the percentage of blastomeres categorized as normal was significantly lower in the FF-MAS 5 microM group (41%) and the FF-MAS 20 microM (29%) group versus the inert (52%) and the vehicle (61%) groups. Significantly reduced cleavage and good quality pre-embryo rates were found in both FF-MAS groups. CONCLUSION: FF-MAS increased the rate of aneuploidy and had detrimental effects on cleavage and pre-embryo development, when exposed both before and after fertilization.

Cinética hormonal (GH, IGF-I) en entrenamiento extensivo de fuerza / Growth hormone and insulin-like growth factor-1 kinetics in extensive strength training

Este trabajo estudia la respuesta de dos hormonas anabólicas: hormona de crecimiento (GH) y factor de crecimiento tipo insulina (IGF-I), en ocho varones, estudiantes de Educación Física, sometidos a un entrenamiento de fuerza con cuatro ejercicios de cargas submáximas con un movimiento de piernas (1/2-squat) y otro de brazos (bench press o bench press inclinado). Cada sujeto hace 70 repeticiones de piernas con un peso medio de 125.63ñ6.65 Kg. y 70 repeticiones de brazos con un peso medio de 56.56ñ7.90 Kg. (1RMBench Press: 79.43ñ11.00 Kg.; 1RM-Bench Press inclinado: 75.12ñ8.78 Kg.; 1RM-1/2Squat: 156.36 ñ8.18 Kg.Se demuestra que aunque el entrenamiento de fuerza de carácter extensivo provoca aumentos significativos de GH e IGF-I inmediatamente después de finalizar el ejercicio, en la fase de recuperación, la GH regresa rápidamente a los niveles iniciales, mientras que la IGF-I no lo hace (AU)

Dolor en región tibial relacionado con el ejercicio. Un enfoque preventivo y terapéutico (I). Concepto, fisiopatología y clínica / The syndrome of the pain in the tibial area related to the exercise. A preventive and therapeutic approach (I). Concept, physiopathology and clinic

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Dolor en región tibial relacionado con el ejercicio. Un enfoque preventivo y terapéutico (II). Diagnóstico, prevención y tratamiento / The syndrome of the pain in the tibial area related to the exercise. A preventive and therapeutic approach (II). Diagnosis, prevention and treatment

El síndrome de dolor en región tibial relacionado con el ejercicio (SDTE), se ha asociado a determinadas alteraciones estructurales o posturales que son preciso identificar a la hora de establecer el diagnóstico. E1 estudio previo de los factores predisponentes nos llevarían a establecer un tratamiento individualizado en función de las alteraciones encontradas en cada deportista en concreto, y sobre todo, nos permitiría aplicar un tratamiento preventivo en todos los casos. En el presente artículo revisamos todos los factores que directa o indirectamente contribuyen a la aparición del síndrome, estableciendo unas pautas concretas de prevención y tratamiento (AU)

FISH analysis for chromosomes 13, 16, 18, 21, 22, X and Y in all blastomeres of IVF pre-embryos from 144 randomly selected donated human oocytes and impact on pre-embryo morphology.

BACKGROUND: The data are compiled from two multicentre, prospectively randomized studies on the effect of follicular fluid meiosis-activating sterol (FF-MAS) on human oocytes. The donated oocytes were exposed either to test doses of FF-MAS or to control solutions. The data from the control groups are presented with chromosomal status of the embryos correlated to embryo morphology. METHODS: The study includes 144 randomly selected donated human oocytes. The nucleus from each blastomere was fixed separately and fluorescence in-situ hybridization (FISH) using seven probes (13, 16, 18, 21, 22, X and Y) was performed. RESULTS: Analysis of 103 pre-embryos containing 479 blastomeres resulted in 424 blastomeres with clear FISH signals. Of these blastomeres, 55% were normal diploid and 45% were abnormal. At a pre-embryonic level, 53% were classified as normal containing >or=50% normal blastomeres while 31% of the pre-embryos were classified as uniformly normal. Abnormality rate was significantly increased in the pre-embryos with unevenly sized blastomeres and with increasing degree of fragmentation at 68 h after fertilization. Applying criteria for good embryo quality significantly increased the rate of chromosomally normal pre-embryos from 53 to 75%. CONCLUSIONS: The data demonstrate the high degree of genetic heterogeneity in a randomly selected pool of donated pre-embryos from an IVF programme. Further, we found that uniformity of blastomere size, degree of fragmentation and cleavage kinetics reflect the cytogenetic status of the pre-embryo and are therefore important in the selection of pre-embryos.

Adaptación del sistema nervioso alentrenamiento / Biological adaptation to endurance training

Cuando se piensa en las modificaciones que pueden producirse en organismos altamente entrenados, indudablemente se dirige el pensamiento hacia el sistema nervioso. Músculo y nervio son unidades indivisibles del movimiento. Es objeto de este trabajo de revisión, analizar la adaptación del sistema neuromuscular al entrenamiento de resistencia. En los últimos 30 años mucho se ha avanzado sobre la modificación, a consecuencia del entrenamiento de resistencia, de las caracteristicas morfológicas y fisiológicas de las fibras musculares, de la placa motora y de las relaciones entre las aferencias (AU)

Perfil antropométrico y fisiológico del piragüista de élite / Anthropometric and physiological profile of elite kayakers

A tenor de la progresiva importancia del deporte del piragüismo en España y de la escasa existencia de estudios realizados sobre el mismo, hemos elaborado un estudio de los parámetros fisiológicos y antropométricos de un grupo de piragüista evaluados en el Centro de Medicina Deportiva del Estadio de la Comunidad de Madrid.Los parámetros cineantropométricos valorados fueron la talla y el peso, la composición corporal con los porcentajes de peso óseo, muscular y graso así como el somatotipo global.Los parámetros funcionales se evaluaron sobre tapiz rodante y sobre ergómetro específico de piragua. En el primero se valoraron los consumos máximos de oxígeno, absolutos y relativos, con la localización de umbrales aeróbico y anaeróbico, ventilación máxima, cociente respiratorio y frecuencia cardiaca. En el kayakergómetro también se midieron parámetros ventilatorios y frecuencia cardiaca, además de potencia movilizada por palada, media de paladas por minuto así como tiempo invertido en realizar los 1000 m totales de la prueba. En este caso también se valoraron los niveles de láctico. El objetivo final es determinar un perfil fisiológico y antropométrico óptimo del piragüista de élite, y así poder tenerlo en cuenta para la futura detección de talentos deportivos (AU)

Large nondipole effects in the angular distributions of K-shell photoelectrons from molecular nitrogen.

Measurements of angular distributions of K-shell electrons photoejected from molecular nitrogen are reported which reveal large deviations at relatively low photon energies (Planck's omega < or = 500 eV) from emission patterns anticipated from the dipole approximation to interactions between radiation and matter. A concomitant theoretical analysis incorporating the effects of electromagnetic retardation attributes the observed large nondipole behaviors in N2 to bond-length-dependent terms in the E1 [multiply sign in circle] (E2,M1) photoelectron emission amplitudes which are indicative of a potentially universal nondipole behavior in molecular photoionization.

Effects of continuous estrogen and estrogen-progestin replacement regimens on cardiovascular risk markers in postmenopausal women.

OBJECTIVE: To evaluate the influence of 2 continuous combined estrogen-progestin replacement products, compared with unopposed estrogen and placebo, on cardiovascular risk markers in postmenopausal women in a randomized, double-blind, placebo-controlled trial. METHODS: Two hundred seventy healthy postmenopausal women were randomly assigned to 1 of 4 treatment groups: placebo, unopposed 17-beta estradiol (1 mg), 1 mg of 17-beta estradiol with 0.25 mg of norethindrone acetate, or 1 mg of 17-beta estradiol with 0.5 mg of norethindrone acetate. The primary outcome variable was change from baseline in low-density lipoprotein cholesterol concentration. Additional outcome variables included changes in other serum lipid levels, hemostatic variables, and indicators of carbohydrate metabolism. RESULTS: The low-density lipoprotein cholesterol level was reduced to a similar degree in all groups receiving active treatment (10%-14% from baseline; P =.001 for 17-beta estradiol with 0.5 mg of norethindrone acetate, P =.004 for 17-beta estradiol with 0.25 mg of norethindrone acetate, and P =. 001 for 1 mg of 17-beta estradiol vs placebo). Compared with unopposed 17-beta estradiol, 17-beta estradiol with 0.5 mg of norethindrone acetate enhanced the reductions in total cholesterol and apolipoprotein B levels (P<.01 vs 17-beta estradiol). 17-beta Estradiol plus norethindrone blunted or reversed the increases in levels of high-density lipoprotein cholesterol, apolipoprotein A-I, and triglycerides produced by 17-beta estradiol alone. Effects of 17-beta estradiol plus norethindrone on hemostatic variables were similar to those of 17-beta estradiol except for factor VII activity, which was significantly reduced with 17-beta estradiol combined with 0.25 mg (P<.01) and 0.5 mg (P<.05) of norethindrone acetate. 17-beta Estradiol plus norethindrone appeared to blunt reductions in C-peptide and insulin levels produced by unopposed 17-beta estradiol but did not elevate these values compared with placebo. CONCLUSIONS: 17-beta Estradiol plus norethindrone produced favorable changes in most cardiovascular risk markers evaluated and has a profile distinct from that of unopposed 17-beta estradiol. The impact of these differences on cardiovascular events warrants investigation. Arch Intern Med. 2000;160:3315-3325.

A combination of low doses of 17 beta-estradiol and norethisterone acetate prevents bone loss and normalizes bone turnover in postmenopausal women.

The effects of 17 beta-estradiol (E2) 1 mg combined with low doses of norethisterone acetate (NETA) on postmenopausal bone loss and turnover were investigated in a 2-year, randomized, double-masked, placebo-controlled trial. A total of 135 postmenopausal women with a lumbar spine bone mineral density (BMD) T-score between -2 and +2 were randomized to daily treatment with an oral tablet of either placebo, E2 1 mg/NETA 0.25 mg, or E2 1 mg/NETA 0.5 mg. Significant (p < 0.001) increases in BMD at the lumbar spine (L1-4) were observed with E2 1 mg/NETA 0.25 mg (5.2%) and E2 1 mg/NETA 0.5 mg (5.4%) compared with placebo (-0.9%). The total hip BMD increased significantly in the E2 1 mg/NETA 0.25 mg (3.1%) and E2 1 mg/NETA 0.5 mg groups (3.3%) compared with placebo. At the femoral trochanter, the increase in BMD in the E2 1 mg/NETA 0.5 mg group (6.3%) was significantly different from the placebo group (0.8%), while that in the E2 1 mg/NETA 0.25 mg group (3.3%) was not. No statistical differences were found between the active groups and placebo for the change in BMD at the femoral neck. Significant increases in BMD at the distal radius and total body were found for both E2 1 mg/NETA 0.25 mg (0.9% and 2.5%, respectively) and E2 1 mg/NETA 0.5 mg (2.1% and 3.0%, respectively) compared with placebo (-0.7% and 0.4%, respectively). At the end of the treatment, urinary pyridinoline type I collagen C-telopeptide had decreased by 65% and 60% in the E2 1 mg/NETA 0.25 mg and E2 1 mg/NETA 0.5 mg groups, respectively, while the mean serum concentrations of osteocalcin had decreased by 39% and 34%, bone-specific alkaline phosphatase by 32% and 29%, and C-terminal propeptide of type I collagen by 21% and 19% had decreased by 34-39%, 29-32%, and 19-21% in the E2 1 mg/NETA 0.25 mg and E2 1 mg/NETA 0.25 mg groups, respectively. In conclusion, combinations of E2 1 mg and NETA 0.25 or 0.5 mg prevent bone loss in postmenopausal women at the lumbar spine, hip, distal radius and total body, and normalize bone turnover.