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Aim The treatment of desmoid tumours (DTs) is controversial. Anti-oestrogen therapy has frequently been used, but clear information of its efficacy is lacking. In this systematic review we have undertaken a comprehensive analysis to assess the effectiveness of anti-oestrogen therapy in terms of ability to induce partial or complete regression of DTs. Method A systematic review of articles published in English between January 1983 and December 2009 was carried out according to the RECIST criteria. A literature search was performed on electronic databases including: United States National Library of Medicine (MEDLINE-PubMed), Excerpta Medica (EMBASE), Cochrane Library and Google search engine. Two-hundred articles dealing with DTs were identified but only fourty-one were were selected as appropriate for the study. The chi-square test was used for statistical analysis. Results Data on 168 DTs treated with anti-oestrogen agents, alone or in combination with nonsteroidal anti-inflammatory drugs, were identified with an overall response rate of 51%. There was no difference in response according to the type of DTs or between different anti-oestrogen therapies. Combination with anti-inflammatory drugs did not improve the outcome. Toremifene was sometimes effective in cases resistant to tamoxifen. Response did not seem to be related to oestrogen receptor status. Conclusions Despite potential inaccuracies in the methodology, the results of the review indicate that anti-oestrogen therapy produces some effect in about one half of patients with DTs. Its indication compared with other treatments is discussed.

Introduction – The popular use of black cohosh products (Actaea racemosa L., syn. Cimicifuga racemosa L.) is growing as the demand for alternatives to estrogen therapy has increased. Critical to safe use is the assurance of unadulterated, high-quality products. Questions have been raised about the safety of black cohosh due to cases of liver toxicity in patients who reported taking it; subsequent evaluation found some products to be adulterated with other related herbal species. Correct plant species identification is a key first step for good manufacturing practices of safe black cohosh products. Objectives – To develop analytical methods which distinguish black cohosh from other species (American and Asian) of Actaea increasingly found as adulterants in commercially available black cohosh products. Material and methods – Fifteen species of Actaea were collected from North America and Asia, and the phytochemical fingerprints of these samples were established using HPLC-PDA and LC-MS techniques. Results – The HPLC and LC-MS fingerprints for polyphenols and triterpene glycosides revealed distinct patterns that make black cohosh clearly distinguishable from most other species of Actaea. Two marker compounds, cimifugin and cimiracemoside F, were found to be important to distinguish black cohosh from most Asian species of Actaea. Formononetin was not found from either Asian or American species of Actaea. Conclusions – Phytochemical fingerprinting is a practical, reliable method for authenticating black cohosh and distinguishing it from other species of Actaea increasingly found as adulterants in commercially available black cohosh products. This should facilitate the continued development of high-quality, unadulterated black cohosh products. Copyright © 2011 John Wiley & Sons, Ltd.

Previous studies in postmenopausal women have reported that estrogen treatment (ET) modulates the risk for developing Alzheimer's disease (AD). It has recently been hypothesized that there may be a "critical period" around the time of menopause during which the prescription of ET may reduce the risk of developing AD in later life. This effect may be most significant in women under 49 years old. Furthermore, prescription of ET after this point may have a neutral or negative effect, particularly when initiated in women over 60-65 years old. In this paper, we review recent studies that use in vivo techniques to analyze the neurobiological mechanisms that might underpin estrogen's effects on the brain postmenopause. Consistent with the "critical period" hypothesis, these studies suggest that the positive effects of estrogen are most robust in young women and in older women who had initiated ET around the time of menopause.

A 72-year-old man with a seminal vesicle carcinoma is reported. The patient was treated by local excision of the tumour and radiotherapy. When the patient deteriorated and radiological and scintographic signs of skeletal metastases developed, hormone therapy (oestrogen) was initiated. Within a few weeks the patient was free from his severe pain. The radiological and scintographic signs of metastases had either diminished in size or disappeared after one year of oestrogen therapy. The patient is still alive and well 2 years after the diagnosis was established.

Oestradiol stimulates growth and development in Turner's syndrome. Previous results with low-dose oestradiol on growth rate are reviewed. The effect of oestradiol in low concentrations on somatomedin generation, GH secretion and directly on osseous tissue, may explain the growth response. The observations presented here of 35 girls treated with 17-beta-oestradiol demonstrated a definite increase in growth rate in the first year of therapy. Bone maturation was accelerated, but a reduction in final height was not found.

While some research has indicated that ovarian hormone therapy (HT) benefits memory and decreases risk of Alzheimer's disease in menopausal women, several newer studies have shown null or detrimental effects. Despite the null and negative cognitive findings, the numerous studies showing positive effects beg the question of what factors determine whether HT acts as a neuroprotectant or a risk factor for brain functioning. Using middle-aged female rats, we directly compared six HTs. We evaluated the effects of ovariectomy, tonic low-dose, tonic high-dose and biweekly cyclic estradiol treatment, as well as whether progesterone altered the effectiveness of any one of these oestrogen regimens. Animals were tested on spatial and complex cued (intramaze patterns) reference memory using variants of the Morris maze. The tonic low-dose and cyclic estradiol treatments improved spatial performance, while the addition of progesterone reversed these beneficial cognitive effects of estradiol. Additionally, all groups learned to locate the platform on the cued task; however, an egocentric circling strategy was used with sham ovary-intact and hormone-replacement groups showing the most efficient search strategy. Although the question of memory retention 8 weeks after the first cognitive assessment was addressed, a large number of animals died between the first and second test, rendering the retest uninterpretable for many group comparisons. Specifically, both doses of tonic estradiol dramatically increased the number of deaths during the 17-week experiment, while the cyclic estradiol treatment did not. Progesterone decreased the number of deaths due to tonic estradiol treatment. Our findings suggest that the dose of estradiol replacement as well as the presence of progesterone influences the cognitive outcome of estradiol treatment. Further, there appears to be a dissociation between HT effects on cognition and mortality rates.

Randomized, controlled trials of estrogen treatment found protective effects of estrogen therapy (ET) on verbal memory in healthy, 45-year-old surgically menopausal women given 17-beta estradiol immediately after surgery. However, no effect was found when conjugated equine estrogens were given to older women years after their surgical menopause. These findings suggest that there is a critical time for the initiation of estrogen following the menopause with regard to its protective effect on memory as well as a specificity of the effect on verbal memory. These factors may explain why no protective effect of ET on cognitive aging was found in the Women's Health Initiative Memory Study.

Sympathetic vasoconstriction is normally attenuated in exercising muscles of young men and women. Recent evidence indicates that such modulation, termed functional sympatholysis, may be impaired in older men. Whether a similar impairment occurs in older women, and what role oestrogen deficiency might play in this impairment, are not known. Based on the strong positive correlation between circulating oestrogen levels and functional sympatholysis previously reported in female rats, we hypothesized that sympatholysis would be impaired in oestrogen-deficient postmenopausal women, and that this impairment would be reversed by oestrogen replacement. To test these hypotheses, we measured vasoconstrictor responses in the forearms of pre- and postmenopausal women using near infrared spectroscopy to detect decreases in muscle oxygenation in response to reflex activation of sympathetic nerves evoked by lower body negative pressure (LBNP). In eight premenopausal women, LBNP decreased muscle oxygenation by 20 ± 1% in resting forearm, but only by 3 ± 2% in exercising forearm (P 0.05). After 1 month of transdermal oestradiol replacement in these women, the normal effect of exercise to blunt sympathetic vasoconstriction was restored (rest, −19 ± 3%; exercise, −2 ± 3%; P < 0.05). These data indicate that functional sympatholysis is impaired in oestrogen-deficient postmenopausal women. The effect of short-term unopposed oestrogen replacement to correct this impairment implicates a role for oestrogen in the sympathetic neural control of muscle haemodynamics during exercise.

Background: Evidence from systematic reviews of observational studies suggests that hormone therapy may have beneficial effects in reducing the incidence of cardiovascular disease events in post-menopausal women, however the results of randomised controlled trials (RCTs) have had mixed results. This is an updated version of a Cochrane review published in 2013. Objectives: To assess the effects of hormone therapy for the prevention of cardiovascular disease in post-menopausal women, and whether there are differential effects between use in primary or secondary prevention.Secondary aims were to undertake exploratory analyses to (i) assess the impact of time since menopause that treatment was commenced (= 10 years versus < 10 years), and where these data were not available, use age of trial participants at baseline as a proxy (= 60 years of age versus < 60 years of age); and (ii) assess the effects of length of time on treatment. Search methods: We searched the following databases on 25 February 2014: Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE and LILACS. We also searched research and trials registers, and conducted reference checking of relevant studies and related systematic reviews to identify additional studies. Selection criteria: RCTs of women comparing orally administered hormone therapy with placebo or a no treatment control, with a minimum of six months follow-up. Data collection and analysis: Two authors independently assessed study quality and extracted data. We calculated risk ratios (RRs) with 95% confidence intervals (CIs) for each outcome. We combined results using random effects meta-analyses, and undertook further analyses to assess the effects of treatment as primary or secondary prevention, and whether treatment was commenced more than or less than 10 years after menopause. Main results: We identified six new trials through this update. Therefore the review includes 19 trials with a total of 40,410 post-menopausal women. On the whole, study quality was good and generally at low risk of bias; the findings are dominated by the three largest trials. We found high quality evidence that hormone therapy in both primary and secondary prevention conferred no protective effects for all-cause mortality, cardiovascular death, non-fatal myocardial infarction, angina, or revascularisation. However, there was an increased risk of stroke in those in the hormone therapy arm for combined primary and secondary prevention (RR 1.24, 95% CI 1.10 to 1.41). Venous thromboembolic events were increased (RR 1.92, 95% CI 1.36 to 2.69), as were pulmonary emboli (RR 1.81, 95% CI 1.32 to 2.48) on hormone therapy relative to placebo. The absolute risk increase for stroke was 6 per 1000 women (number needed to treat for an additional harmful outcome (NNTH) = 165; mean length of follow-up: 4.21 years (range: 2.0 to 7.1)); for venous thromboembolism 8 per 1000 women (NNTH = 118; mean length of follow-up: 5.95 years (range: 1.0 to 7.1)); and for pulmonary embolism 4 per 1000 (NNTH = 242; mean length of follow-up: 3.13 years (range: 1.0 to 7.1)). We performed subgroup analyses according to when treatment was started in relation to the menopause. Those who started hormone therapy less than 10 years after the menopause had lower mortality (RR 0.70, 95% CI 0.52 to 0.95, moderate quality evidence) and coronary heart disease (composite of death from cardiovascular causes and non-fatal myocardial infarction) (RR 0.52, 95% CI 0.29 to 0.96; moderate quality evidence), though they were still at increased risk of venous thromboembolism (RR 1.74, 95% CI 1.11 to 2.73, high quality evidence) compared to placebo or no treatment. There was no strong evidence of effect on risk of stroke in this group. In those who started treatment more than 10 years after the menopause there was high quality evidence that it had little effect on death or coronary heart disease between groups but there was an increased risk of stroke (RR 1.21, 95% CI 1.06 to 1.38, high quality evidence) and venous thromboembolism (RR 1.96, 95% CI 1.37 to 2.80, high quality evidence). Authors' conclusions: Our review findings provide strong evidence that treatment with hormone therapy in post-menopausal women overall, for either primary or secondary prevention of cardiovascular disease events has little if any benefit and causes an increase in the risk of stroke and venous thromboembolic events. © 2015 The Cochrane Collaboration.

Effects of swimming training and estrogen therapy on the vascular reactivity of hypertensive ovariectomized rats: role of renin angiotensin system Glaucia R Abreu, Nazare S Bissoli, Ana Ligia R Car...

Aim. To investigate the development in women's attitude to hormone replacement therapy, and the change in views concerning positive and negative effects. Methods. National cohort study based on telephone interviews in 1990 and 1997, of women randomly sampled from the Norwegian telephone book ( n =1019 and 1003). The same questions were asked in both studies. Results. In 1997, more women stated radio and television, doctors, friends and relatives as sources of information. The general attitude to hormone replacement therapy had become significantly more positive, and the respondents reported a higher level of information than in 1990. However, some misunderstandings about estrogen therapy still remain; the proportion of women who believed that estrogen treatment reduced the risk for breast cancer increased from 4% in 1990 to 15% in 1997. About one third of women aged 60 or more are current or past users. More than 60% of the women in the youngest age group state that they will consider use of estrogen repl...

summary Anamnestic and clinical investigations were made for 230 postmenopausal women to determine whether the alveolar height in edentulous jaws is associated with the time that the subjects have consumed artificially fluoridated drinking water. The duration of possible hormone replacement therapy was also considered. The results of the present study support those of previous studies which have shown that the effect of systemic factors dominates the final stage of residual ridge resorption. According to this study, artificially fluoridated water may also reduce the degree of residual ridge resorption, the impact of which first becomes manifest when most of the ridge has disappeared.

An estimated 32,000 American men will die of prostate cancer this year. Local prostate cancer may be successfully treated by radical prostatectomy or radiotherapy. Advanced cases may necessitate the use of hormonal ablation with bilateral orchiectomy, an approach that is regarded as the gold standard of therapy but not always the preferred treatment of patients. Oestrogen therapy is an alternative but is associated with side effects, such as hot flushes and gynaecomastia, which frequently lead to treatment cessation. Luteinising hormone-releasing hormone (LHRH) analogues work by initially producing a surge of androgen, followed by a down-regulation in hormone production to effect a medical castration. Various groups have studied the effects of androgen blockade administered as monotherapy and as combination therapy (LHRH analogue plus antiandrogen). The National Cancer Institute intergroup protocol 0036, which is the largest cooperative study to date of patients with advanced prostatic cancer, showed that combination therapy with leuprolide and flutamide offered greater benefit in both time to disease progression and median survival while circumventing tumour flare and its associated symptoms. Thus, combination therapy for total androgen ablation may become the new treatment standard for advanced prostatic cancer, pending further studies in the efficacy and cost-effectiveness of all available treatments.

Three groups of girls with mean final height predictions of 185.3 cm were treated in 3-week cycles with 0.25, 0.5, or 1.0 mg of ethinylestradiol. The three groups were comparable with regard to chronological age, bone age, height prediction, and duration of treatment. Reduction in final height of 5.5-5.9 cm/group in comparison with the initial prediction was observed in all treated groups. This reduction appeared independent of estrogen dose. Subsequent height increases were limited to about 50% of the predicted gain in all cases. In a comparable group of untreated tall girls the prediction method overestimated the final height by 1.2 cm. In the groups receiving 1.0 and 0.5 mg EtE2 a significant reduction in IGF-I levels was achieved within three to six months after the start of estrogen therapy.

Cardiovascular disease is a major concern in dialysis patients, with many risk factors present in this population. An elevated lipoprotein (a) level is one such factor. Since estrogen levels are low in women on dialysis and estrogen therapy lowers lipoprotein (a) levels, wouldn't it be reasonable to treat most female dialysis patients with estrogens?

EDITORIAL COMMENT: This pharmacology comment is published to inform readers of possible complications of bromocriptine therapy and to remind them that most women who elect not to breast-feed do not require drug therapy to suppress lactation, especially if breast-feeding has not been attempted. As noted in a previous comment (IA), suppression of lactation by oestrogen therapy was discontinued 24 years ago when it was found to be associated with thromboembolism. We then realized how few women were troubled by severe breast engorgement. Opinion has hardened against the routine use of drug therapy for inhibition of ‘physiological’ lactation

Therapeutic use of oestrogens by males with carcinoma of the prostate leads to testicular atrophy with markedly reduced spermatogenesis after only 21 d (Oshima et al. 1974). Treatment for over a year results in paucity of germ cells, vacuolation of Sertoli cells and reduction in Leydig cells (Lu & Steinberger 1978, Smith & Urry 1985). There is, apparently, no information on the histology of the human testis after more than 1 year oestrogen therapy. We here report changes in testes from five transsexuals treated for periods of up to 5.5 years.

A double-blind study of cyclofenil plus diazepam compared to placebo was carried out in 30 postmenopausal patients at the Gynaecologic Clinic of Sao Paulo University Medical School. All patients had had amenorrhoea for at least one year before the trial. Kupperman Menopausal Index (KMI), FSH, LH, prolactin and oestradiol blood levels and vaginal smears were the data analysed. Cyclofenil 400 mg plus diazepam 10 mg po daily was the prescribed standard dose, which relieved the main symptoms of the menopausal syndrome. With the dose schedule used, neither blood hormone levels nor vaginal smears data showed any statistical difference before and after treatment. Also, no important side-effects were observed.

The criteria for the diagnosis of progression of prostatic cancer after primary treatment by androgen suppression (oestrogen escape) were studied in 30 patients. Objective criteria are essential for this diagnosis and in this study the bone scan was the most useful criterion. Twenty-one of these patients had a secondary orchiectomy: one patient showed a partial objective response and 3 had a subjective response. It is concluded that an orchiectomy following failed primary oestrogen therapy is an ineffective procedure and therefore unjustifiable and that alternative treatments must continue to be evaluated.

SUMMARY Measurements of plasma ‘cortisol’ and metacarpal mineral content were made in seventy-two postmenopausal women of whom one half had been taking 20-40 μg mestranol daily for 1-3 years. Urinary free ‘cortisol’ (UFC) was also measured in just over one half of these women. Significant increases in plasma ‘cortisol’ and metacarpal mineral content were found in the mestranol treated women. The greatest bone mineral response was found in those women with plasma ‘cortisol’ concentrations in the range 36-45 μg/100 ml. A significant inverse relationship was found between UFC and metacarpal mineral change. These findings imply that failure of the skeleton to respond to oestrogen therapy might result from a relative increase in adrenocorticoid activity. It is suggested that the measurement of plasma ‘cortisol’ and UFC may be of value in monitoring the treatment of patients on long-term oestrogen therapy.

Summary Patients with prostatic cancer, receiving oestrogen therapy were found to have elevated serum Cortisol levels and lymphopenia. Oestrogens are known to have a profound effect on the immune system; the possibility that this effect is mediated through the adrenal cortex is discussed. The significance of these findings, however, remains to be determined.

Summary— Serial transrectal needle biopsies were taken from 146 patients (657 specimens) with advanced prostatic cancer (T3/T4, M1/MO) admitted to a trial of two forms of oestrogen therapy. Histological grading by Gleason and Mostofi techniques on the initial biopsy showed no correlation either with extent of disease or its eventual outcome on treatment. Change in grade was dissociated from the response of bone metastases to hormone treatment and did not appear to influence survival. However, the prognosis of 16 patients showing clearance of tumour from their serial biopsies was generally good.

SUMMARY A case of bilateral breast metastases developing in a patient with carcinoma of the prostate while on oestrogen therapy is described. Differentiation between prostatic metastases and primary breast tumours under these circumstances is important as the treatment for each is different. Such differentiation may be difficult by conventional histological techniques, but histochemical analysis can resolve the problem, as was possible in this case.

Orchidectomy and oestrogen therapy were introduced simultaneously in 1941 for patients with advanced carcinoma of the prostate by Charles Huggins and his colleagues (Huggins and Hodges, 1941; Huggins, Stevens and Hodges, 1941; Huggins, Scott and Hodges, 1941). Oestrogen therapy has always been more popular than orchidectomy, and the first purpose of this article is to examine, and question, the justification for this. The second purpose is to question the widelyheld belief that, as regards hormonal suppression, subcapsular orchidectomy is an incomplete form of castration.

Two patients with prostatic adenocarcinoma are reported whose metastases harbored large foci of squamous cell carcinoma. The prostatic origin of such areas was proven by immunoperoxidase staining for prostatic acid phosphatase (PAP) as well as the identification of transition zones between adenocarcinoma and squamous cell carcinoma. The possible role of estrogen therapy in inducing the squamous change is discussed.

The experiences with estrogen therapy in old age are absolutely minimal regarding cancer risk. When Mir jam Furuhjelm updated estrogen replacement therapy during the climacterium several years ago she was in terra incognita. Her aspirations met an enormous response. In a similar way, long-term treatment with estrogens is an unknown territory now.

SUMMARY In castrated animals and hypogonadal men other workers have shown an LH surge following oestrogen administration similar to that found in the normal female. However, there is no evidence that this can be achieved in intact males. We have therefore studied male transsexual patients before and after chronic oestrogen therapy given for at least three months to feminise the body habitus before undergoing plastic surgery. Subjects were assessed for the acute effects of oestradiol valerate on sex steroid hormone levels and gonadotrophin responses to gonadotrophin releasing hormone. The results showed that longterm treatment could transform the normal male pattern of a suppressive eifect of oestrogen on gonadotrophin release to one where the oestrogen increased LH levels and amplified the effect of LHRH on gonadotrophin release. This pattern is similar to that found in normal women and indicates that longterm oestrogen treatment to males can feminise gonadotrophin responses.

Inhalt Es wird ern Gerat zur Messung des eleletrischen Widerstandes des Vaginalschleimes beim Rind beschrieben. An 3 Kuhen wurde die Leitfahigkeit des Scheidenschleimes wahrend des Zyklus, nach Ovariektomie und nach Ovariektomie plus Ostrogenapplikation gemessen. Der Widerstand betrug im Diostrus 57, 1 ± 0, 6 Ohm (x±sx), wahrend der Hochbrunst 31, 38 and 39 Ohm (Differenz zu Diostrus P ≦ 0,01), nach Ovariektomie 68, 6 ± 0, 2 Ohm und nach Ovariektomie plus Ostrogenapplikation (2 Kuhe) 36,5 and 44,5 Ohm. Contents An instrument for measuring the electrical resistance of vaginal mucus in cattle is described. The conductivity of the mucus of 3 cows was measured during the oestrous cycle, after ovariectomy, and after combined ovariectomy and oestrogen therapy. The resistance in dioestrus amounted to 57,1 ± 0,6 Ohms (x ± sx), during peak oestrus 31, 38 and 39 Ohms (difference from dioestrus P ≤ 0,01), after ovariectomy 68,6 ± 0,2 Ohms and after combined ovariectomy and oestrogen therapy (2 cows) 36,5 and 44,5 Ohms.

The effect of castration on serum high-density lipoprotein (HDL) cholesterol was studied in 11 women with fairly regular menstruation. The HDL cholesterol levels before and one month after castration did not differ significantly. The effect of intramuscular estrogen therapy on HDL cholesterol was investigated in six castrated women. Ten days after injections of both 10.0 mg of estradiol valerate and 2.5 mg of estradiol benzoate plus 10.0 mg of estradiol phenylpropionate, HDL cholesterol was increased significantly. Fifteen days later, HDL cholesterol levels returned to the pretreatment values.

SYNOPSIS Two patients with long standing, incapacitating migraine were found to have premature ovarian failure. Administration of 1.25 mg of conjugated estrogen daily for 23 days of every month caused almost complete disappearance of the headaches. Attempts to reduce the dose to 0.625 mg daily were followed by recurrences which were controlled by increasing the dose to previous levels. A trial of estrogen therapy seems to be warranted in some patients with migraine, where estrogen deficiency is suspected.