The Safety of Local Hormonal Treatment for Vulvovaginal Atrophy in Women With Estrogen Receptor-positive Breast Cancer Who Are on Adjuvant Aromatase Inhibitor Therapy: Meta-analysis.

Atrophic vaginitis is a relatively common adverse effect of aromatase inhibitors used as an adjunctive treatment for breast cancer. Vaginal estrogen therapy is a treatment option, but the safety of its use in estrogen receptor-positive breast cancer remains understudied. The aim of our study was to determine the safety of local hormonal treatment of vulvovaginal atrophy in women treated with aromatase inhibitors. Our meta-analysis was based on a systematic search of the literature and selection of high-quality evidence. The safety of local hormonal therapy of vaginal atrophy in women on aromatase inhibitors were summarized using calculators built by the authors; heterogeneity was assessed by the Cochrane Q test and I2 values. Several types of bias were assessed; publication bias was calculated by a funnel plot and the Egger regression. Eleven studies fulfilled the inclusion criteria for our study. After 8 weeks of local hormonal treatment, there was no change in the serum levels of luteinizing hormone and estradiol, whereas sex hormone binding globulins were low, and follicle stimulating hormone was almost doubled compared with the baseline. Adverse effect rates of vaginal discharge, facial hair growth, urinary tract or yeast infection, and vaginal or vulvar itching and/or irritation did not show significant changes in the sensitivity analysis, with exception of a single trial. Current evidence suggests that vaginal estrogen administration in postmenopausal women with a history of breast cancer is not associated with systemic absorption of sex hormones and may provide indirect evidence for the safety of their use.

Translation of the Medical Fear Survey to Serbian: psychometric properties.

BACKGROUND: Medical Fear Survey (MFS) is an instrument designed for measuring fear of medical and related treatments. OBJECTIVE: Aim of the present study was MFS translation into Serbian, measurement of its psychometric properties and MFS validation using other Blood-injury-injections and related stimuli instruments that have been translated from English into Serbian. METHOD: After obtaining permission from the author of the original MFS, double forward translation from English to Serbian and backward translation to English were conducted in ten steps, according to International Society for Pharmacoeconomics and Outcomes Research (ISPOR) guidelines. Reliability, factorial analysis and concurrent validation of Serbian version of MFS were conducted on a sample of 485 medical or pharmacy students at University of Kragujevac, Serbia. RESULTS: Serbian version of MFS showed high internal consistency with a Cronbach's alpha 0.968 and good temporal stability after testing-and-retesting (Spearman's correlation coefficient 0.838, and intraclass correlation coefficient 0.877). Factorial analysis confirmed the same five factors demonstrated in the original English version: fear of mutilated bodies (10 items), fear of blood (11 items), fear of injections and blood draws (9 items), fear of sharp objects (10 items), and fear of medical examinations and physical symptoms (10 items). The total score of MFS correlated significantly with the total scores of Injection Phobia Scale-Anxiety (Spearman's correlation coefficient 0.391, p <0.001), Blood/Injection Fear Scale (Spearman's correlation coefficient 0.502, p <0.001) and Medical Avoidance Survey (Spearman's correlation coefficient 0.396, p <0.001). CONCLUSIONS: Serbian version of the 50-item MFS showed similar psychometric properties as the original English version of this scale, with the same factorial structure. It could be used for measurement of fear of medical and related treatments in Serbian socio-cultural milieu, preferably self-administered. Hippokratia 2016, 20(1): 44-49.

Effect of X-rays on selenium content in rat jaws.

It is known that X-radiation of the growing jaws results in impaired dental development. We investigated the role of selenium (Se) in radiation-induced dental growth retardation. The heads of 8-day-old female rats were irradiated with a single dose of 9.6 Gy of X-rays. Another group of animals was irradiated under the same conditions but, for radioprotective purposes, were also in deep hypothermia during radiation exposure. Nonirradiated animals served as controls. The Se content in the upper and lower jaws was analyzed by hydride generation atomic absorption spectrophotometry. In the upper jaws of the animals exposed to irradiation, the Se concentration was significantly lower than in those irradiated under conditions of hypothermia (p < 0.05), although both groups showed no significant difference in Se concentration when compared to nonirradiated controls. In the lower jaws, the concentration of Se was significantly reduced in the irradiated group when compared with controls and the rats irradiated under conditions of hypothermia (p < 0.05). There was no significant difference in Se concentration between rats irradiated under conditions of hypothermia and nonirradiated controls. There was no significant change in Se concentration in the jaws of the rats protected by hypothermia during radiation exposure compared with nonirradiated controls. Although Se loss in the irradiated bone could be prevented by hypothermia, we could not prove that Se loss per se is the cause of growth retardation nor that its retention has a radioprotective effect.

Regulation of ovarian hyperluteinization.

Adult female rats with neonatally damaged posterior hypothalamus, made by a transversal cut, were investigated. Plasma levels of prolactin (PRL), gonadotropic hormones (GTH) and female gonadal steroids (GS) were determined by radioimmunoassay. The animals were sacrificed, at the ages of 4 and 6 months and their hypothalamus, pituitary gland, ovary and uterus were examined using light microscopy. The results can be summarized as follows: body mass of animals, with damaged posterior hypothalamus, was significantly reduced. Masses of luteinized ovaries were increased and uterine tissues decreased. Serum levels of PRL were significantly increased and luteinizing hormone (LH) decreased. Ultrastructural changes in the corpora lutea (CL), previously described, showed clear signs of their reduced capacities to produce GS, both estradiol (Oe) and progesterone (Pg) per total ovarian mass. However, prostaglandin 2 alfa (PGF2alpha) known as a luteolytic factor, was also diminished in the evidently retarded endometrium. As a result of decreased plasma values of LH, Pg and PGF2 alpha, luteolysis of CL in hyperluteinized ovaries did not occur, and their new generations were accumulated during subsequent cycles. The character of interruption and recovery of aminergic and peptidergic neurons, involved in regulation of hypothalamic-pituitary gonadal axis and feed-back effects of steroid hormones, require further studies.

The effects of continuous light and darkness on the activity of monoamine oxidase A and B in the hypothalamus, ovaries and uterus of rats.

For assessing monoamine oxidase (MAO-A and -B) activities in the hypothalamus, ovaries and uterus, mature female rats were exposed to either continuous light or dark over 6 weeks. Confirming previous studies, continuous light induced constant estrus in all animals. The majority of animals kept under continuous dark during the six weeks remained mostly in diestrus with estrus appearing sporadically. The endocrinological function of the ovaries was disturbed by continuous light, which resulted in the development of polycystic ovaries, their morphological appearance being not significantly affected by continuous dark. Hypothalamic MAO-A activity was markedly reduced under the influence of both light (p < 0.05) and dark (p < 0.01). The activity of hypothalamic MAO-B was reduced only under the influence of dark (p < 0.01). In the ovaries, no significant differences were detected in either MAO-A or -B activity as a result of these environmental manipulations. In the uterus of rats exposed to continuous light which developed polycystic ovaries, MAO-A activity was significantly lower (p < 0.05) in comparison to either intact controls or rats exposed to continuous dark. These results demonstrate that chronic changes in photoperiodicity may considerably influence MAO-A activity and to a lesser extent MAO-B activity dependent on the tissue studied.

Basal and stress induced concentrations of adrenal gland catecholamines and plasma ACTH during aging.

Basal and stress levels of catecholamines (CA) in the adrenal glands, and circulatory levels of adrenocorticotropic hormone (ACTH) were examined in female Wistar rats aged 1, 3, 10 and 24 months. Our data showed reduction in basal dopamine (DA) concentration in adrenal glands and an increase in this catecholamine in response to stress at all ages (1, 3, 10, 24 months). The greatest levels of basal norepinephrine (NE) and epinephrine (E) concentrations in the adrenal glands were noted in intact rats at the age of 24 months. On the other hand, the stress response of NE and DA had a tendency to fall, reaching basal values at the age of 10 and 24 months of age. Basal circulatory levels of ACTH showed a reduction with age. The stress response of ACTH was reduced in animals aged 10 and 24 months. Reduced basal values of adrenal DA and increased NE and E values, suggest that there is increased adrenomedullar activity at the age of 24 months. On the other hand, the reduced or even absent stress response of NE and E observed in the adrenals, in 10 and 24 months old rats, may be of interest in considering the ability of these animals for adaptation. Basal and stress values of plasma ACTH are significantly reduced with the onset of senescence in female rats.

The effect of constant light on the concentration of catecholamines of the hypothalamus and adrenal glands, circulatory hadrenocorticotropin hormone and progesterone.

The participation of adrenocorticotropic hormone (ACTH) in the control of adrenal glands and the regulation of ACTH secretion in female rats exposed to constant light for six weeks were studied. A significant increase of plasma ACTH (p < 0.05) in rats exposed to constant light is in correlation with an increase of epinephrine (E) synthesis in adrenal gland (p < 0.05) when compared to intact controls. On the other hand, ACTH secretion is in inverse relation with a significantly reduced concentration of dopamine (DA) and norepinephrine (NE) in hypothalamus (p < 0.05). In addition, higher concentration of plasma ACTH in rats exposed to constant light through its effect on the adrenal cortex is responsible for the appearance of polycystic ovaries. As a contribution to this assumption is the result showing an increased concentration of serum progesterone in rats exposed to constant light when compared to corresponding controls which is probably of adrenal origin. These results indicate an inverse relationship between plasma ACTH concentrations and DA and NE concentrations in hypothalamus and that the hypothalamo-pituitary-adrenal axis has a significant role in the regulation of ovarian function.

Catecholamines in hypothalamus, ovaries and uteri of rats with precocious puberty.

The concentration of catecholamines in the hypothalamus and reproductive organs of rats with hypothalamic lesions placed on the day of birth was investigated. In an attempt to contribute to the discussion concerning the role of catecholamines in regulation of puberty, the aim of this study was to examine the content of hypothalamic, ovarian and uterine catecholamines in female rats with precocious vaginal opening. The animals were sacrificed on the day of precocious puberty, which occurred at the age of 25.71 +/- 0.98 days. The data obtained were compared with intact (pubertal) controls obtained on the day of vaginal opening (40.13 +/- 1.35 days) as well as in infantile intact controls of corresponding age of the lesioned animals. In the ovaries of both animals (i.e. lesioned and sacrificed on day of vaginal opening and the infantile controls of corresponding age), small and medium sized follicles were present. Ruptured follicles were evident only in the pubertal controls. The mass of ovaries and uteri from lesioned rats was also significantly lower than in the pubertal controls. Concentrations of norepinephrine in both ovaries and uteri on the day of vaginal opening of the animals with posterior hypothalamic lesions and of infantile controls, was significantly higher than in pubertal controls on the day of vaginal opening. Epinephrine was significantly higher in the uterine tissues of lesioned and infantile controls as compared to pubertal animals. The levels of dopamine and norepinephrine in the hypothalamus of lesioned and pubertal controls on the day of vaginal opening were significantly higher than in infantile controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Luteinization of ovaries and gonadotrophin and prolactin secretion in rats with posterior hypothalamic lesions.

Posterior hypothalamic lesions restricted to the mammillary body in newborn rats evoked significantly elevated serum prolactin concentrations (P < 0.05) in adult females in the afternoon of proestrous (16.00 h), while at the same time serum LH values appeared significantly depressed (P < 0.05) as compared to controls. FSH concentrations were not affected. Parallel to changes in hormonal pattern, the ovaries of the lesioned animals grew to excessive dimensions due to the accumulation and persistence of numerous corpora lutea (CL) (syndrome of hyperluteinized ovaries). The results suggest that the posterior hypothalamus can regulate prolactin and LH secretion and that the fate of CL is associated with a quantitative ratio in the circulation of at least two hormones, prolactin and LH.

The effects of X-ray irradiation of the head region of eight-day-old rats on the development of molar and incisor teeth.

The effects of irradiation on the development of molars and incisors up to the age of 57 days was studied applying locally a single dose of 9.6 Gy of X-rays to the head region of eight-day-old female rats. Radiography of jaws revealed the absence of the third molar in all irradiated rats, as a result of germ stunting which was, at the moment of irradiation, in the phase of histodifferentiation. In the case of the first and second molar, being at the time of irradiation in the phase of root formation, changes were noted in the development and morphological features of the roots. In animals sacrificed 18 days after irradiation, the radiographs of jaws showed a break in the continuity of the incisors located under the mesial root of the first molar. In all animals the break in continuity of the incisors became macroscopically visible between the 28th and 42nd day after irradiation. 15 days after the loss of incisors, the incisival functional occlusion was restored in all animals.