The lived experience of the early postoperative period after colorectal cancer surgery.

Colorectal cancer is one of the most common cancer diagnoses and undergoing colorectal cancer surgery is reported to be associated with physical symptoms and psychological reactions. Social support is described as important during the postoperative period. The purpose of this paper was to describe how patients experience the early postoperative period after colorectal cancer surgery. Interviews according a phenomenological approach were performed with 13 adult participants, within 1 week after discharge from hospital. Data were collected from August 2006 to February 2007. Analysis of the interview transcripts was conducted according to Giorgi. The essence of the phenomenon was to regain control over ones body in the early postoperative period after colorectal cancer surgery. Lack of control, fear of wound and anastomosis rupture, insecurity according to complications was prominent findings. When caring for these patients it is a challenge to be sensitive, encourage and promote patients to express their feelings and needs. One possibility to empower the patients and give support could be a follow up phone call within a week after discharge.

Specificity of neonatal, androgen-induced imprinting of hepatic steroid metabolism in rats.

The specificity of the neonatal, andreogen-induced, irreversible programming of hepatic steroid metabolism in the rat was investigated. 5-alpha-Dihydrotestosterone propionate and estradiol benzoate were as efficient as testosterone propionate in inducing a male type of liver metabolism in the adult animal, whereas epitestosterone propionate, etiocholanolone propionate, and o,p'-DDT were practically inactive in this respect. These findings indicate that different mechanisms are involved in neonatal imprinting of hepatic steroid metabolism and in the well-known neonatal androgenic and estrogenic induction of persistent estrus and acyclic gonadotropin secreqion.

Estrogen and hearing: a summary of recent investigations.

Is the female sex steroid estrogen the key to preserved hearing in the aging human? This question remains unanswered, but hearing loss is more profound in elderly males than females. There are also well-known sex differences in the auditory brainstem response (ABR), i.e. women have shorter latencies than men. Moreover, menopausal women who are administered hormone replacement therapy have slightly better hearing than those who are not, and women with Turner's syndrome (45,X), who are biologically estrogen-deficient, show longer ABR latencies and early presbyacusis. These findings are also supported by animal experiments. When boosted with estrogen or testosterone the non-reproductive female midshipman fish alters its inner ear auditory mechanism so that it can hear the male's hum-like call. If estrogen receptor beta is knocked out in mice, severe progressive hearing loss occurs, leading to early deafness. In apparent contradiction to these findings, there have been case reports suggesting that hormone replacement therapy and oral contraceptive use can lead to hearing loss, but of another type, namely acute sudden deafness. Such contradictory aspects of the action of estrogen are commonly found and may spring from the fact that there are two estrogen receptors, alpha and beta, both of which are present in the inner ear of mice, rats and humans. Knowing how sex steroids can alter hearing ability may give important clues as to how estrogen can preserve hearing in humans. In this review we present a summary of current knowledge about hearing and estrogen.

The metabolism of 4-androstene-3,17-dione by isolated rat hepatocytes. Maintenance of the sex differences in culture.

Hepatocytes from adult rats were isolated and cultivated as primary monolayers for 3 days in a medium containing only 1% homologous serum. The metabolism of 4-androstene-3,17-dione was followed in hepatocytes from male, female and hypophysectomized animals. It was found that immediately after preparation, 5alpha-reductase and 16alpha-hydroxylase activities were present in the cells in amounts comparable to those found in microsomal preparations from liver homogenates. After 3 days in culture, these enzyme activities had decreased to about half the values measured on day 0. During this time the sexual differences in steroid metabolism in the cells were stable, i.e. there was no detectable induction of 16alpha-hydroxylase in cells from female animals, and the relative sex difference in 5alpha-reductase activity persisted.

Partial masculinization of rat liver enzyme activities following treatment with FSH.

The metabolism of 4-(4014C)androstene-3,17-dione and 5alpha-(4-14C)androstene-3alpha, 17beta-diol was studies in the microsomal fraction and that of 4-(4-14C) androstene-3,17-dione in the 105,000 times g supernatant fraction of livers from castrated male and female rats treated with LH and FSH. Administration of LH led to significant decreases in 17-hydroxysteroid reduction and 7alpha-hydroxylation of 4-androstene-3,17-dione in both male and female rats and in 6beta-hydroxylation of 4-androstene-3,17-dione in female rats. FSH on the other hand specifically stimulated (masculinized) the following sex-dependent hydroxylations: 16alpha-hydroxylation of 4-androstene-3,17-dione in female rats and 2alpha-, and 2beta- and 18-hydroxylation of 5alpha-androstane-3alpha,17beta-diol in male rats. The metabolism of 4-androstene-3,17-dione and 5alpha-androstane-3alpha,17beta-diol was also studied in castrated male and female rats given testosterone propionate and in castrated female rats given testosterone propionate in combination with LH or FSH. It was shown that neither LH nor FSH could compensate for the relative androgen-unresponsiveness exhibited by female as compared to male rats. It is concluded that FSH but not LH may participate in the regulation of sex-dependent hydroxylase systems in rat liver.?2,Author

Feminization of hepatic steroid metabolism in male rats following electrothermic lesion of the hypothalamus.

The metabolism of [4-14C]androst-4-ene-3,17-dione, [4-14C]5alpha-androstane-3alpha,17beta-diol and [1,2-3H]5alpha-androstane-3alpha,17beta-diol, 3,17-disulfate in the 105,000 X g supernatant and microsomal fractions of liver was studied in male and female rats after electrothermic lesion of the hypothalamus including the median eminence. Following electrothermic lesion, hepatic steroid metabolism in male rats was generally "feminized" (increased 5alpha-reduction and decreased 6beta- and 16alpha-hydroxylation of 4-androstene-3,17-dione, decreased 2alpha-, 2beta-, 18- and 7beta-hydroxylation of 5alpha-androstane-3alpha, 17beta-diol and induced 15beta-hydroxylation of 5alpha-androstane-3alpha,17beta-diol,3,17-disulfate), whereas hepatic metabolism in female rats remained essentially unchanged. Previous investigations have pointed to the occurrence of a sex-specific secretion of "feminizing factor" from the female pituitary that is responsible for the "feminization" of the basically "masculine" type of metabolism characterizing the rat liver. Taken together with these findings, the present results indicate that the release of the pituitary "feminizing factor" is controlled by means of a release-inhibiting factor from the hypothalamus. This factor is not secreted in female rats; it is suggested that its secretion in male rats is turned on as a result of neonatal imprinting by testicular androgens.

Desmopressin tablets in the treatment of severe nocturnal enuresis in adolescents.

BACKGROUND: In recent years the treatment of primary nocturnal enuresis (PNE) with desmopressin (DDAVP) has been promising. The route of administration until now had been intranasal, but because the tablets were introduced for the treatment of diabetes insipidus they have also become available for the treatment of PNE. OBJECTIVES: To find the optimal dosage of desmopressin tablets and to compare desmopressin's efficacy with placebo in a group of adolescents with severe monosymptomatic enuresis. The long-term safety of desmopressin was also studied in the same group of patients. METHODS: The effect of oral desmopressin (1-deamino-8-D-arginine-vasopressin) (DDAVP tablets, Minirin) was investigated in 25 adolescents (ages 11 to 21 years) with severe monosymptomatic nocturnal enuresis. The first part of the dose-ranging study comprised a single-blind dose titration period, followed by a double-blind, crossover efficacy period comparing desmopressin with placebo. The final part was an open long-term study consisting of two 12-week treatment periods. The efficacy of the drug was measured in reductions of the number of wet nights per week. RESULTS: During the first dose-titration period, the majority of the patients were given desmopressin 400 micrograms, and the number of wet nights decreased from a mean of 4.9 to 2.8. During the double-blind period, a significant reduction of wet nights was observed (1.8 vs 4.1 for placebo). During the two long-term periods, 48% and 53% of the patients could be classified as responders (0 to 1 wet night per week) and 22% and 23.5% as intermediate responders (2 to 3 wet nights per week). No weight gain was observed due to water retention. After cessation of the drug, 44% of the patients had a significant decrease in the number of wet nights. CONCLUSIONS: Oral desmopressin has a clinically significant effect on patients with PNE, and therapy is safe when administered as long-term treatment.

Sleep of children with enuresis: a polysomnographic study.

OBJECTIVE: To evaluate relationships between bladder voiding and sleep in children with enuresis. METHODS: Polysomnographic recordings were obtained from 25 children, aged 7 to 17 years, with monosymptomatic nocturnal enuresis. During 52 recorded nights, 37 enuretic events were detected. Responders (n = 7) and nonresponders (n = 16) to desmopressin treatment were compared. RESULTS: The mean latency between sleep onset and the first bladder voiding was 3 hours 20 minutes (SD = 2 hours 5 minutes). The number of voidings were 19, 7, 10, and 1 occurring during stages 2, 3, and 4, and rapid-eye movement sleep, respectively. Desmopressin responders were found to void during the early or late part of the night, whereas the voidings of the nonresponders were dispersed evenly throughout the night (chi2 = 8.09). CONCLUSIONS: The enuretic event is a predominantly non-rapid eye movement sleep phenomenon. Responders and nonresponders to desmopressin treatment void during different parts of the night.

Developmental, diurnal and oestrous cycle-dependent changes in the activity of liver enzymes.

The metabolism of [4-14C]4-androstene-3, 17-dione was studied in the 105000 g microsomal and supernatant fractions of liver from developing rats of both sexes. The following enzyme activities were measured: 5beta-reductase (supernatant fraction) and 5alpha-reductase, 17alpha- and 17beta-hydroxysteroid reductases, 6beta-, 7alpha- and 16alpha-hydroxylases (microsomal fraction). The activities of the 3alpha- and 3beta-hydroxysteroid reductases were estimated by calculating the ratios of 3alpha-: 5alpha- and 3beta-: 5alpha-reduced metabolites formed, respectively. Most enzyme activities present at birth (i.e. 5beta-reductase, 5alpha-reductase, 17beta-hydroxysteroid reductase, 6beta- and 7alpha-hydroxylase) increased until 20 days of age in both male and female rats. Between 20 and 30 days of age a number of masculine metabolic characteristics appeared in both sexes, i.e. the 16alpha-hydroxylase and the 17alpha-hydroxysteroid reductase were induced, the 5beta-reductase activity rapidly increased and the 5alpha-reductase activity slightly decreased. During a third period beginning 30 days after birth the adult male enzyme activity pattern was completed by the induction of 3beta-hydroxysteroid reductase and a further increase in the activity of 16alpha-hydroxylase. After 30 days of age a feminine type of liver metabolism also rapidly developed in female rats; the 16alpha-hydroxylase and the 17alpha-hydroxysteroid reductase activities disappeared, the 6beta-hydroxylase and the 5beta-reductase activities decreased and the 5alpha-reductase activity increased six times. The developmental patterns of enzyme activities in the rat liver are consistent with a first developmental phase (0-30 days of age) independent of hypophysial control and probably determined primarily by the genome of the liver cell and a second phase (from 30 days onwards) with increasing sexual differentiation under hypophysial control. This control is mediated by some kind of feminizing factor in female rats and possibly by some kind of androgen-elicited secretion of masculinizing factor(s) in male rats. The metabolism of [4-14C]4-androstene-3, 17-dione was also studied during different times of the day and during different phases of the oestrous cycle. The 16alpha-hydroxylase activity showed a diurnal variation with higher values at noon than at midnight. The 5beta-reductase activity reached a maximal activity during metoestrus.

Reduction of androstenedione by skin in vitro and serum levels of gonadotrophins and androgens in men with hypospadias.

The reduction of 4-[1,2-3H]androstene-3,17-dione (androstenedione) in vitro by scrotal skin was measured in samples from nine men (16--34 years old) with hypospadias and from ten male control subjects. The reduction of androstenedione was also studied in axillary and upper arm skin of seven control subjects. Androstenedione was reduced to material with chromatographic characteristics of 5 alpha-androstane-3,17-dione and to 3 alpha- and 3 beta-hydroxy-5 alpha-androstan-17-one. No difference in 5 alpha-reductase activity (defined as the sum of these three metabolites formed) was found in scrotal skin from hypospadic and control men. The mean concentration of 5 alpha-dihydrotestosterone in serum from men with hypospadias was lower than that in serum from control subjects (P less than 0.01). The mean ratio of the serum concentrations of testosterone and 5 alpha-dihydrotestosterone was higher in hypospadic men than in control subjects (P less than 0.05). No differences between the two groups were found in the mean serum concentrations of LH, FSH, prolactin, dehydroepiandrosterone, androstenedione, testosterone or testosterone-binding globulin.

Metabolism of androstenedione in skin and serum levels of gonadotrophins and androgens in prepubertal boys with hypospadias.

The metabolism of 4-[1,2-3H]androstene-3,17-dione in the prepuce, axillary skin and skin from the arm was investigated in 27 boys operated for phimosis (controls) and 13 unselected boys with hypospadias (a congenital defect of the male urethra). In all types of skin investigated, androstenedione was metabolized to 5alpha-androstane-3,17-dione, 3alpha-hydroxy-5alpha-androstan-17-one, 3beta-hydroxy-5alpha-androstan-17-one and testosterone. Conversion to testosterone was found in the prepuce of two out of 11 boys with hypospadias. Mild forms of hypospadias in the age group 1--4 years had a higher level of 5alpha-reductase activity in the prepuce than controls in the same age group (P less than 0.05); no such differences were found in the few severe cases of hypospadias in this group. No other differences in 5alpha-reductase activity were found between hypospadic boys and controls. The ratio of 5alpha-reductase activity in the prepuce: 5alpha-reductase activity in skin from the arm was significantly higher (P less than 0.05) in hypospadic boys than in controls in the age group 1--4 years. Serum levels of LH and FSH were the same in normal and hypospadic boys but the concentration of prolactin in the serum was lower in boys with hypospadias compared with control subjects in the age group 1--4 years (P less than 0.005). No differences were found in serum concentrations of androstenedione, testosterone, oestradiol and testosterone-binding globulin.

Sex-dependent prepubertal gonadotrophin surges in the rat.

The concentrations of LH and FSH were measured by radioimmunoassay in sera from immature male and female rats of various ages. Fairly high levels of FSH were found in both sexes at birth but lh was not detected. FSH peaks appeared in the male at 13 and 19 days of age and in the female at 13 and 17-19 days of age. LH was undetectable in the male before 12 days of age, rose to a peak (440 plus or minus 60 (S.D.) ng/ml) at 13 days of age and fell below the detection level again between 15 and 25 days of age. A further increase then occurred which almost reached adult levels. LH was first detectable in the female rat at 11 days of age with a peak value of 130 plus or minus 35 ng/ml at 12 days. The hormone was undetectable on days 14 and 15, rose to a second peak on day (148 plus or minus 56 ng/ml), and was again absent between 19 and 25 days of age. The concentration rose, as in the male, between days 25 and 28 to a level similar to that of the adult. The results show sexual differences in prepubertal gonadotrophin surges. The LH peak at 12-13 days in both sexes appears to be light-dependent. The FSH peak at this time was affected by light but was not strictly light-dependent.

Partial feminization of hepatic steroid metabolism in male rats after neonatal administration of cyproterone acetate.

The metabolism of (4-14C)4-androstene-3,17-dione, (4-14C)5alpha-androstane-3alpha, 17beta-diol and (1,2-3H)5alpha-androstane-3alpha, 17beta-diol 3,17-disulphate was studied using the microsomal fraction and the metabolism of (4-14C)4-androstene-3,17-dione was studied using the 105 000 g supernatant fraction of liver from male and female rats aged 5 months that had been treated with cyproterone acetate before (from day 13 of pregnancy) and after birth (until 3 weeks of age). Nearly all sex-dependent enzyme activities in the treated male rats were changes in a direction characteristic of female rats: 5alpha-reductase active on 4-androstene-3,17-dione increased in activity whereas 3beta- and 17alpha-hydroxysteroid reductases and 6beta- and 16alpha-hydroxylases active on 4-androstene-3,17-dione and 2alpha-, 2beta- and 18-hydroxylases active on 5alpha-androstane-3alpha,17beta-diol decreased in activity. Enzyme activities not under gonadal control, i.e. 3alpha- and 17beta-hydroxysteroid reductases active on 4-androstene-3,17-dione and 7alpha-hydroxylase active on both 4-androstene-3,17-dione and 5alpha-androstane-3alpha, 17beta-diol, were not affected by cyproterone acetate. The liver enzyme activities in treated female rate were generally not affected although significant effects were noted in two cases; in one of these (17alpha-hydroxysteroid reductase) a testosterone-like effect was observed. The results obtained are probably best explained in the following way: treatment with theanti-androgen during the neonatal period results in less efficient imprinting of the hypothalamo-hypophysial system leading to less pronounced masculine setting of sex-dependent enzyme levels and also to a relative androgen unresponsiveness. It is suggested that the biochemical methods used in the degree of neonatal sexual differentiation of the hypothalamo-hypophysial system than biological and psychological methods previously available.

The prevalence of urogenital symptoms in postmenopausal women.

Lower urogenital tract disorders, such as vaginal athropy, urethritis, dyspareunia, recurrent urinary tract infections and urinary incontinence symptoms, are more prevalent in postmenopausal women. While these disorders are attributed to the ageing process as well as estrogen deficiency, knowledge of the relationship between estrogen status and symptomatology is scarce and hard to investigate due to the complexity of the problem. Little is known about the epidemiology of urogenital symptoms and their relationship to estrogen status and treatment. Studies of the prevalence of urogenital symptoms in postmenopausal women have been rare and results divergent. Through reviewing existing literature and relating findings to our own prevalence studies of 61-, 71- and 81-year-old women, we can conclude that many of the symptoms accounted for in our study are those known to be due to the loss of estrogen and easily dealt with by estrogen therapy. However, there is a need for more adequate information about postmenopausal symptoms and the effect of estrogens, as only a minority of postmenopausal women are currently treated.

Prevalence of genitourinary and other climacteric symptoms in 61-year-old women.

In a population-based cohort study, 1280 women, aged 61, were interviewed regarding their genitourinary and other postmenopausal symptoms by means of an anonymous questionnaire. The group selected was to constitute all women of 61 years of age living in Uppsala county, Sweden. The response rate was 84%. All were postmenopausal women. Seventy-three percent of the women answering admitted some degree of urinary incontinence and 33% more severe degree. Forty-nine percent reported some degree of stress incontinence, 25% a more severe degree. Thirty-one percent experienced urge incontinence, 14% severely. A minority (4%), had had more than two urinary infections during the last year. The majority (67%) had changed urinating habits, going to the toilet at night and a minority complained of increased frequency of micturation (8%). Of the participating women, 59% were still sexually active, 43% had trouble with vaginal dryness and 10% with vaginal burning. Vasomotor problems such as hot flushes (30%), daily (33%) and nightly sweating (36%) were all common troubles. Forty-seven percent of the women had asked for medical help for estrogen deficiency problems, 82% were satisfied with the help they had received. Thirty-four percent were on estrogen therapy, 16% had systemic therapy 18% low dose estrogen treatment.

Prevalence of postmenopausal symptoms in two age groups of elderly women in relation to oestrogen replacement therapy.

A cross-sectional study of the whole female population of ages 71 and 81 years in a defined part of Sweden was undertaken to investigate the prevalence of oestrogen treatment and postmenopausal symptoms. A questionnaire was mailed to 2245 women, of whom 1084 (87%) aged 71 years and 611 (62%) aged 81 years left evaluable responses. Of the responding 71- and 81-year-old women 25 and 16%, respectively were receiving oestrogen, and 4 and 2% of all women of the respective age groups were on systemic treatment. Nearly half of all the women reported urinary incontinence, which was considerate for approximately half of these women. Five and 11% of the respective age groups had experienced more than two urinary tract infections (RUTI) in the last year. RUTI had occurred both in the oestrogen-treated group and in the non-treated group. Vegetative symptoms were still encountered among these elderly women. Previous fractures were frequent, being experienced after menopause by 29 and 39% of the 71- and 81-year-old women respectively. Thirty-five and 39% of the women in respective age group had sought medical help for postmenopausal symptoms. Of the women with moderate, severe or unbearable urinary incontinence, 60 and 66% of the respective age groups had sought medical help. In only few of the totals of women on oestrogen had the treatment a complete effect. Only 2 and 1% of all women in respective age group had been offered and undergone surgery for their urinary incontinence.

Otological problems in children with Turner's syndrome.

Ear and hearing disorders are common problems among girls and women with Turner's syndrome. During infancy and childhood the girls often suffer from repeated attacks of acute otitis media and later in life the women frequently complain of a rapid onset of social hearing problems due to sensorineural hearing impairment. A study of 56 girls aged 4-15 years with Turner's syndrome was performed to investigate the prevalence of eardrum pathology and hearing impairment in young children and teenagers with Turner's syndrome. A possible relation to karyotype was also investigated. A high prevalence (61%) of recurrent acute otitis media was found in the study group and 32% had been treated with ventilation tubes. Fifty-seven percent showed eardrum pathology, such as effusion, myringosclerosis, atrophic scars, retraction pockets and perforations. Auricular anomalies were noted in 23% of the cases, most commonly in the 45, X group. The audiometric analysis showed conductive hearing loss (air-bone gap > 10 dB HL) in 43% and the typical sensorineural dip in the middle frequencies was found in 58% of the girls, of whom the youngest was 6 years old. Four percent were using hearing aids. The data of this study further confirm that the dip is progressive over time and may be detectable as early as at the age of 6, giving a chance to predict a future hearing loss. The findings emphasize the importance of regular otological examinations and audiological evaluations of all girls with Turner's syndrome early in life.

Characterization of hearing in an X,0 'Turner mouse'.

Turner's syndrome is due to total (45,X) or partial (mosaicism) loss of one X-chromosome. The main features are short stature, ovarian dysgenesis with no estrogen production and infertility. In addition to ear and hearing disorders, middle ear problems including acute/serous otitis media and chronic middle ear disease are frequent. Sensorineural hearing loss is often seen with a dip in the mid-frequencies and also an early high frequency loss. In this study, middle-and inner-ear pathology was characterized using physiological and morphological techniques in a 'Turner mouse' that has been generated with the chromosomal aberration X,0. Otitis media was found in some of these X,0 animals, a symptom that is seldom found in control animals. The auditory brainstem responses (ABR) of the Turner mouse showed a progressive hearing loss in the high frequency region that exceeded the normal age-related hearing loss of control mice and increased latencies of the first ABR wave. Outer hair cell loss was apparent in the cochlear basal turn of Turner mice. Decreases in the amplitude of distortion product otoacoustic emissions were correlated with the loss of ABR threshold sensitivity. These results indicate that hearing problems in the Turner mouse seems to be of cochlear origin with an eighth nerve component. This Turner mouse model appears to have ear and hearing problems quite similar to humans and can therefore be used as a model to determine the auditory pathology underlying this syndrome.

Effect of estrogen and antiestrogens on the estrogen receptor content in the cochlea of ovariectomized rats.

Older women in the normal population tend to develop less severe hearing loss as compared to males in the same age. In Turner syndrome (45,X), estrogen deficiency is one of the predominant problems. Ear and hearing problems are common among these patients. Does estrogen have an impact on the hearing organ? Twenty-four rats were ovariectomized and treated with vehicle (controls), estradiol or selective estrogen receptor modulators such as tamoxifen and ICI182780, in order to study the effects on the estrogen receptor levels and distribution in the inner ear. The cochleas were stained immunohistochemically using antibodies against estrogen receptor alpha and beta. No major difference in estrogen receptor content in the cochleas was observed among groups. There was however a potential down regulation of estrogen receptor alpha in the marginal cells of stria vascularis in the rats that were substituted with ICI182780 (pure antiestrogen) as compared to those given estradiol or tamoxifen. When investigating the tissues with light microscopy no change in inner ear anatomy could be observed.

Mapping of estrogen receptors alpha and beta in the inner ear of mouse and rat.

The sex hormone estrogen is classically known to influence growth, differentiation and function of peripheral tissues of both the female and male reproductive tract, mediated through the estrogen receptors alpha and beta. The influence of estrogens on the ear and hearing is yet not fully investigated, though some studies have suggested that estrogens may influence hearing functions. The aim of this study was to map eventual estrogen receptors in the inner ear in mouse and rat. Paraffin embedded sections of mouse and rat inner ear were immunostained with antibodies against estrogen receptors alpha and beta. Estrogen receptors alpha and beta containing cells were found in the inner ear, showing a unique distribution pattern, both in the auditory pathways and in the water/ion regulating areas. The presence of estrogen receptors indicates that estrogens may have an effect on the inner ear and hearing functions.