Localized advanced carcinoma of the prostate: radiation therapy versus hormonal therapy.
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Cancer of the breast. Endocrine and hormonal therapy.
Additive hormonal therapy remains the treatment of choice for disseminated breast cancer in postmenopausal women. Patients with hormone-dependent tumors receive excellent and long-lasting palliation from alterations in the hormonal milieu. Now that hormone receptor assays are clinically available, responses can be accuratedly predicted in a large percentage of cases. Tables 11--6 is a summary of additive hormonal therapy in postmenopausal patients. Endocrine ablative therapy remains of primary importance in premenopausal women because of the superior results, but androgens or antiestrogens may be helpful when patients are not surgical candidates. Castration continues to be the initial approach, with adrenalectomy or hypophysectomy reserved for promising candidates. In postmenopausal women the initial choice is estrogens. The exceptions are those patients with metastases limited to bone, when androgens excel because of an equivalent objective response and superior subjective and metabolic effects. Patients who respond to estrogens and then progress are observed for a rebound regression following the discontinuation of estrogen therapy. Whereas some who do not respond to androgens will respond to estrogens, the converse does not appear to be true (Kennedy, 1974). Currently progestins are the secondary hormonal agent of choice in postmenopausal women, but they may be displaced by antiestrogens as more data become available. In general, if a patient's tumor lacks estrogen receptors or the patient fails to respond to an adequate trial of endocrine or hormonal therapy, one should proceed directly to cytotoxic chemotherapy. A suggested plan for the integration of endocrine with hormonal therapy and both with other forms of palliation is diagrammed at the end of Chapter 12.
Adrenal Cortex Hormones↗
Long-term hormone therapy for perimenopausal and postmenopausal women.
BACKGROUND: Hormone therapy is widely provided to control menopausal symptoms and has been used for the management and prevention of cardiovascular disease, osteoporosis and dementia in older women. This is an updated version of a Cochrane review first published in 2005. OBJECTIVES: To assess the long-term effects of prolonged use (at least one year) of hormone therapy on mortality, cardiovascular outcomes, cancer, gallbladder disease, fractures and cognition in perimenopausal and postmenopausal women. SEARCH METHODS: We used the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, three other databases and two trial registers, together with reference checking, citation searching and contact with study authors to identify the studies included in the review. The latest search date was 26 September 2024. SELECTION CRITERIA: We included randomised, double-blind trials in which peri- or postmenopausal women took hormone therapy or placebo for at least one year. We included various oestrogen formulations, with or without progestogens. We focused on studies assessing hormone therapy's effects on long-term clinical outcomes, including death, coronary events and cancer. Hormone therapy's efficacy in managing menopausal symptoms was beyond the scope of this review, and is assessed in other Cochrane reviews. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risk of bias and extracted data. We calculated risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data, along with 95% confidence intervals (CIs). We assessed the certainty of the evidence using GRADE. MAIN RESULTS: We included 24 studies - with two newly added in this update - involving 45,660 participants. We derived nearly 70% of the data from two well-conducted studies: the Heart and Estrogen/progestin Replacement Study (HERS 1998) and the large, multi-component Women's Health Initiative research programme, which included two hormone therapy arms (WHI 1998). Across all the studies, most participants were postmenopausal American women with one or more comorbidities. The mean participant age in most studies was over 60 years. Only one included study focused on perimenopausal women. We present full results for all included studies with available data in the main review. The results presented below are drawn from WHI 1998, in which the combined hormone therapy arm and the oestrogen-only arm were run concurrently, with women assigned to the appropriate trial based on their uterus status. One study with 16,608 postmenopausal women with an intact uterus compared combined continuous hormone therapy (conjugated equine oestrogen and medroxyprogesterone acetate) to placebo, and measured outcomes at an average of 5.6 years of follow-up. Based on this study, combined continuous hormone therapy probably makes little to no difference to the risk of a coronary event (RR 1.17, 95% CI 0.95 to 1.44; moderate-certainty evidence). It may increase the risk of stroke (RR 1.39, 95% CI 1.09 to 2.09; low-certainty evidence) and venous thromboembolism (RR 2.03, 95% CI 1.55 to 6.64; low-certainty evidence). Compared to placebo, combined continuous hormone therapy probably increases the risk of breast cancer (RR 1.27, 95% CI 1.03 to 1.56; moderate-certainty evidence) and probably makes little to no difference to the risk of lung cancer (RR 1.06, 95% CI 0.77 to 1.46; moderate-certainty evidence). It may increase gallbladder disease requiring surgery (RR 1.64, 95% CI 1.30 to 2.06; 14,203 participants; low-certainty evidence), and probably reduces the risk of all clinical fractures (RR 0.78, 95% CI 0.71 to 0.86; moderate-certainty evidence). One study including 10,739 postmenopausal women who had undergone a hysterectomy compared oestrogen-only (conjugated equine oestrogen) hormone therapy to placebo, and measured outcomes at an average of seven years' follow-up. Based on this study, oestrogen-only hormone therapy probably makes little to no difference to the risk of coronary events (RR 0.94, 95% CI 0.78 to 1.13), venous thromboembolism (RR 1.32, 95% CI 1.00 to 1.74) and breast cancer (RR 0.79, 95% CI 0.61 to 1.01), all with moderate-certainty evidence. It may make little to no difference to the risk of lung cancer (RR 1.04, 95% CI 0.73 to 1.48; low-certainty evidence). Oestrogen-only hormone therapy probably increases the risk of stroke (RR 1.33, 95% CI 1.06 to 1.67) and gallbladder disease requiring surgery (RR 1.78, 95% CI 1.42 to 2.24), and probably reduces the risk of all clinical fractures (RR 0.73, 95% CI 0.65 to 0.80), all with moderate-certainty evidence. We judged most included studies to have a low risk of bias for most domains. The overall certainty of evidence for the main comparisons was moderate. The main limitation was that only about 30% of women were 50 to 59 years old at baseline, the age group most likely to consider hormone therapy for vasomotor symptoms. AUTHORS' CONCLUSIONS: Long-term follow-up of women using hormone therapy suggests that the risk profiles vary between combined hormone therapy and oestrogen-only therapy. Oestrogen-only hormone therapy probably makes little to no difference to coronary events, and probably increases the risk of stroke and gallbladder disease. It probably makes little to no difference in the risk of breast cancer, and probably reduces the risk of all fractures. Combined hormone therapy may increase the risk of thromboembolism and probably increases the risk of breast cancer. These results should be interpreted with caution as they are based on one study using oral hormone therapy, which may not represent the risks of the hormone therapy currently used in clinical practice.
Humans↗
Overnight polygraphic studies of infantile spasms--influence of hormone therapy on sleep states, pulse, respiration and seizure activities.
The influence of hormone therapy on sleep states, pulse, respiration and seizure activities of infantile spasms was examined by means of overnight sleep polygraphy. Also the correlation between the changes of these parameters and the prognosis was investigated. The results were as follows: 1) In all cases, the awake time of TIB during hormone therapy was longer than before hormone therapy. The reduction of REM sleep time of SPT and lowering of REM density were remarkable during hormone therapy in cases with delayed psychomotor development as compared with cases with a considerable degree of psychomotor development. During hormone therapy, the NREM sleep time of SPT was shortened in cases with ACTH therapy, and prolonged in case with hydrocortisone therapy. 2) During hormone therapy, the pulse rate increased significantly in cases with a considerable degree of psychomotor development, but decreased significantly in cases with delayed psychomotor development. The change of respiratory rate by hormone therapy was not remarkable in all cases. 3) In cases with hypsarhythmic EEG records, the number of spikes decreased drastically by hormone therapy. In the case with EEG record of focal spikes, the number of spikes increased by hormone therapy. From the results mentioned above, the mechanism for effectiveness of hormone therapy and correlation between the administration of hormone therapy and prognosis was discussed.
Adrenocorticotropic Hormone↗
Long-Term Outcomes of Radiation Monotherapy Versus Combined Radiation Monotherapy + Hormone Therapy in Low-Risk Early-Stage Breast Cancer Patients 70 Years or Older After Breast-Conserving Surgery.
PURPOSE: Standard therapy for breast cancer after breast-conserving surgery is radiation therapy (RT) plus hormone therapy (HT). For patients with a low-risk of recurrence, there is an interest in deescalating therapy. METHODS AND MATERIALS: A retrospective study was carried out for patients treated at the Swedish Cancer Institute from 2000 to 2015, aged 70 years or older, with pT1N0 or pT1NX estrogen receptor-positive and ERBB2-negative unifocal breast cancer without positive surgical margins, high nuclear grade, or lymphovascular invasion. RESULTS: Patient numbers were sufficient to carry out analyses for RT + HT (n = 307) and RT alone (n = 148). The median follow-up was 9.6 years. There were no statistically significant differences in adjusted overall survival (OS), disease-specific death, progression-free survival (PFS), distant recurrence, and second primary cancers with RT monotherapy compared with RT + HT. Cumulative rates of all of these outcomes were <5%, even at 15 years of follow-up, regardless of treatment, greatly outweighed by the incidence of death from other causes in this elderly population. In matched analysis, we calculated a hazard ratio of 1.12 (95% CI, 0.82-1.53) for RT versus RT + HT for OS and a hazard ratio of 1.12 (95% CI, 0.82-1.53) for RT versus RT + HT for PFS. CONCLUSIONS: Our data suggest that elderly, low-risk breast cancer patients have similarly high OS and PFS with low rates of local recurrence, distant recurrence, and death from breast cancer with much higher rates of death from competing causes, whether treated with RT or HT + RT. These patients are likely to die of other causes without disease recurrence, regardless of which of these treatments is used. Thus, they may benefit from the administration of more modern forms of breast irradiation without the need for adjuvant systemic hormone therapy. A detailed analysis of which clinical, pathologic, genomic, and comorbidity variables are needed to select these patients.
Humans↗
Correlation between clinical response to hormone therapy and steroid receptor content in prostatic cancer.
Hormonal therapy is the dominating form of treatment for prostatic carcinoma. The majority of cases (80%) are well controlled for varying times with this regimen. However, thus far there have been no adequate methods to predict in which cases hormonal therapy is of less benefit. Measurement of cancer tissue content of intracellular hormone receptors constitutes progress toward a more individualized therapy in prostatic carcinoma. In this study biopsies from 16 cancer patients were taken before therapy was given, and the specimens were analyzed with regard to content of specific methyltrienolone-binding sites. A correlation has been made between receptor content and clinical response to hormonal therapy in each case. Twelve specimens contained measurable amounts of steroid receptors. Of these, one patient died during irradiation therapy before onset of hormonal treatment. However, of the remaining 11 patients, 9 responded well to hormones (9/11 approximately 82%). The two receptor-positive nonresponders had the lowest measurable receptor levels in the series. Four specimens contained no detectable amounts of receptors. Three of these patients showed no response to therapy (3/4 = 75%) but one was "false negative." Our data indicate that steroid receptor analysis may become a valuable diagnostic tool in individualizing the therapy for prostatic cancer.
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PKCζ, CTNNBIP1 and ALDH1A3 Expression in Luminal B Breast Cancer Indicates Decreased Hormone Therapy Effectiveness.
BACKGROUND/AIM: The role of catenin β interacting protein 1 (CTNNBIP1), a negative regulator of the canonical Wnt/β-catenin signaling pathway, in luminal A and B breast cancer stem cells treated with hormone therapy is unknown. This study investigated the relationship between CTNNBIP1 and aldehyde dehydrogenase 1 family member A3 (ALDH1A3) expression and its impact on disease-specific survival in luminal A and B breast cancer. Given that high protein kinase ζ (PKCζ) expression, together with elevated CTNNBIP1 or ALDH1A3, is linked to poor prognosis in luminal B tumors, we also examined their combined influence. MATERIALS AND METHODS: Gene expression and clinical data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC; n=2,509) were analyzed using Kaplan-Meier and Cox proportional hazards models. Findings were validated with The Cancer Genome Atlas Pan-Cancer Atlas (TCGA; n=1,084). RESULTS: CTNNBIP1 high ALDH1A3 high indicated a poor prognosis in patients with luminal B breast cancer treated with hormone therapy in the METABRIC dataset and aromatase inhibitors as hormone therapy in the TCGA data set, suggesting that high CTNNBIP1 and ALDH1A3 expression contributed to decreased effectiveness of hormone therapy in patients with luminal B breast cancer. PKC ζ high CTNNBIP1 high ALDH1A3 high was associated with a poor prognosis in patients with luminal B breast cancer treated with hormone therapy and aromatase inhibitors, suggesting that high PKC ζ , CTNNBIP1 and ALDH1A3 expression contributed to decreased effectiveness of hormone therapy in patients with luminal B breast cancer. CONCLUSION: PKC ζ and CTNNBIP1 may be involved in the progression of ALDH1A3-positive luminal B breast cancer. In luminal B breast cancer, PKC ζ , CTNNBIP1 and ALDH1A3 could serve as molecular drug targets and prognostic biomarkers to predict the effectiveness of hormone therapy.
ALDH1A3↗
[The effectiveness ot thyroid-hormone therapy following goiter-resection].
The effectiveness of a postoperative thyroid-hormone therapy in preventing a goiter-recidiv was investigated two years after goiter-resection. Of 3381 patients with goiter, who were operated on in the years 1964 to 1973 in the Surgical Department of the Krankenhaus Nordwest in Frankfurt/Main, Germany, 129 patients who were operated on in the first six months of 1969, were questioned and examined in a follow-up study. A rezidiv-goiter was found in 4, 6 p.c. of patients. If only palpable recidiv-goiters are taken into consideration 2, 3 p.c.), patients without postoperative thyroid-hormone therapy developed a recidiv goiter twice as often as patients with thyroid-hormone therapy.
Adolescent↗
Relationship of prior hormonal therapy to subsequent estramustine phosphate treatment in advanced prostatic cancer.
The relationship of prior hormonal therapy to subsequent response on estramustine phosphate (Estracyt) was examined in 107 patients with advanced prostatic cancer treated in two different Phase II chemotherapy trials. In both trials patients with the longest prior hormonal treatment were the least likely to respond to estramustine phosphate. Patients in the series from the National Prostatic Cancer Project with a response classification to prior hormonal therapy had only a 26 per cent response to subsequent estramustine phosphate therapy, whereas 40 per cent of those with no prior response to hormonal therapy responded to estramustine phosphate. This latter group had the shortest average disease duration from diagnosis. The sample of prostate cancers studied appeared to include groups that were sensitive to both hormones and cytotoxic activity as well as to either of these two alone. These data support the contention that estramustine phosphate may act both as an estrogenic and a cytotoxic agent.
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Relationship between menopausal hormone therapy and incidence risk of breast cancer: systematic review and meta-analysis.
BACKGROUND: Menopausal hormone therapy (MHT) is widely prescribed for alleviating menopausal symptoms. Prior studies have mainly focused on individual hormone therapy formulations. This meta-analysis comprehensively synthesized evidence across various regimens to systematically evaluate the association between MHT and breast cancer risk. MATERIALS AND METHODS: We systematically searched CNKI, Wanfang, PubMed, and Web of Science from inception through August 2024. Eligible studies examining breast cancer risk following MHT were independently screened and assessed by two reviewers. The review and meta-analysis followed PRISMA guidelines. RESULTS: Thirty-four studies were included. The random-effects model showed a significant but heterogeneous overall association (OR = 1.15, 95% CI: 1.09-1.22; I² = 92.4%). Subgroup analysis identified hormone type, use status, and region as key determinants (P for interaction < 0.001). Stratification by hormone type resolved much of the heterogeneity, revealing risk confined to estrogen-progestin therapy (EPT; OR = 1.44, 95% CI: 1.26-1.64), while estrogen-only therapy (ET) showed no overall association (OR = 1.00, 95% CI: 0.91-1.10). Study type, region, and sample size were significant effect modifiers. For ET, randomized controlled trials demonstrated a protective effect (OR = 0.78, 95% CI: 0.70-0.87), contrasting with neutral findings from observational studies. CONCLUSIONS: MHT is associated with a modest but significant increase in breast cancer risk, primarily driven by EPT. This risk was not observed with ET in observational studies, though trials suggested a protective effect. Crucially, the association shows marked geographical heterogeneity, indicating risk is modified by regimen and regional factors.
Humans↗
Randomized sequential hormonal therapy vs adrenalectomy for metastatic breast carcinoma.
One hundred sixty-one postmenopausal and 65 premenopausal women, a total of 226 patients with metastatic breast carcinoma, were included in this randomized study to evaluate the merits of adrenalectomy as the primary mode of therapy as compared to the customary sequential hormonal manipulation. The 145 evaluable postmenopausal patients were randomized as follows: (1) primary additive hormone therapy first followed by adrenalectomy and (2) primary adrenalectomy followed by chemotherapy and/or additive hormone therapy. When 76 patients in group 1 were compared with 70 patients in group 2 regarding their survival time, there was no essential difference, but the response rate was 20% vs 38.6%, a significant difference. The 55 evaluable premenopausal women were randomized into two groups: (1) oophorectomy followed by adrenalectomy; (2) adrenalectomy-oophorectomy as primary mode of therapy. The response rate in group 1 was 17.4% as compared with 41.9% in group 2, but again there was no difference in the survival time among these two groups. When sequential hormonal manipulation was utilized, only one-third of these patients were subjected to adrenalectomy because of their rapidly deteriorating condition. Adrenalectomy performed as a secondary procedure showed a lower response rate but the total survival time was comparable with primary adrenalectomy patients.
Adrenalectomy↗
Estrogen receptors and responses to chemotherapy and hormonal therapy in advanced breast cancer.
To determine the correlation between the estrogen-receptor status and responses to chemotherapy or hormonal therapy, we retrospectively analyzed the clinical data of 143 patients with advanced breast cancer. Receptor contents were determined by a sucrose-gradient method and designated arbitrarily as "rich" or "poor". The response rate to chemotherapy was significantly higher in receptor-rich tumors (86 per cent) than in receptor-poor tumors (36 per cent) (P less than 0.001). Patients with receptor-rich tumors also responded favorably to hormonal therapy. However, there was no correlation between the responses to hormonal therapy and to chemotherapy when they were used sequentially, a phenomenon that may be attributed to the changes in tumor receptor content during the clinical course. These data suggest that separate factors associated with the response to chemotherapy may coexist with estrogen receptors in breast cancer.
Adult↗
[On the structural changes induced in adenomyosis uteri and endometriosis externa by hormonal therapy (author's transl)].
This study was undertaken to determine whether the hormonal sensitivity of the endometrium might be a measure of the effectiveness of hormonal therapy for adenomyosis and endometriosis. Accordingly, the effects of endogenous and exogenous hormones on the endometrium, adenomyosis, and endometriosis were correlated. The results revealed that, depending on where the ectopic endometrial tissue was located and on the type (duration and intensity) of hormonal treatment, the functional response of the endometriosis varied from that of the endometrium. The variations, however, can be predicted. The response of adenomyosis to hormonal stimulation was most like that of the endometrium. Endometriosis of the ovary often revealed an excessive response to stimulation, especially after gestagens. The other types of extrauterine foci of endometriosis, however, reacted only weakly to hormonal therapy. Important prognostic consequence for therapy can be drawn from the results.
Abdominal Muscles↗
Liver cell adenoma associated with oral contraceptive hormone therapy.
A patient receiving oral contraceptive hormone therapy developed a hepatic adenoma. Widespread haemorrhages, which were apparently unrelated to trauma, developed in the adenoma. Attention is drawn to the increasing incidence of Pill-associated hepatic tumours, and to the possibility of a fatal haemorrhage.
Adult↗
Long-term survival after hormonal therapy for stage D prostatic cancer.
Hormonal therapy occasionally produces long-term survival of men with metastatic carcinoma of the prostate. To identify which patients will benefit for long intervals a retrospective analysis was done on 56 men with stage D carcinoma of the prostate treated between 1963 and 1968. Of this group 5 patients lived longer than 10 years. We were unable to identify clinical or pathologic characteristics that would have indicated which patients would have done well.
Adenocarcinoma↗
[Hormone profiles and hormone therapy in early pregnancy (author's transl)].
Hormone profiles in early pregnancy were established in 67 women and correlated to simultaneously performed ultrasonic examinations. Normal values for human chorionic gonadotropin (HCG), human chorionic somatotropin (HCS), oestradiol (E2) and progesterone (P) were established from the data obtained in 30 early pregnancies which culminated in the birth of a living child. Lowered HCG values were found in 17 out of 23 pregnancies which ended in miscarriage. In these cases ultrasonic examination failed to detect any heart action. Lowered HCS values after the 9th week of pregnancy are also certain proof of missed abortion. P and E2 values are shown to be a parameter reflecting activity of the corpus luteum graviditatis. In clomiphene- and gonadotropin-induced pregnancies higher values were found than in pregnancies managed by substitution treatment with twice weekly 10 mg oestradiolvalerianate + 500mg 17alpha-hydroxyprogesteronecapronate. Lowered P and E2 values with HCG values in the normal range indicate imminent insufficiency of the corpus luteum graviditatis. Pros and cons of hormonal therapy in early pregnancy are discussed.
Abortion, Missed↗
[Hormone therapy of the juvenile angiofibroma (author's transl)].
Four juvenile angiofibromas were examined with the electron microscope. Preceding the operation a hormonal therapy with stilbestrol disphosphate (Cytonal, Honvan) was carried out in the cases. The therapeutical effect after application of this drug is clearly correlated to especial changes in histology and cytology. The changes comprise reactions of the vascular component and of the stromal fibroblasts. Endothelial cells and pericytes show a markedly diminished cellular activity, a proliferation of vascular wall cells is not to be proved. The stromal fibroblasts may predominantly be classified as fibroblasts with histiocyte-like features, at which the organelle equipment speaks for a high activity of their metabolism. Furthermore an increased number of myofibroblasts and smooth muscle-like elements are encountered in the stroma. The striking diminution of lesion size and the reduction of disposition to bleeding from the beginning of the hormone therapy is suggested as a direct consequence of cellular contraction. Additionally alterations of synthesis of collagen fibers and ground substance by fibroblasts with histiocyte-like features contribute to a further gradual decrease of the growths.
Adolescent↗
Hormone therapy and affect.
This study investigated the influence of hormone therapy on affect in a double blind crossover trail. The sample consisted of 49 women who had previously undergone hysterectomy and bilateral oophorectomy. Therapy consisted of 3 mth each of ethynyl oestradiol-50 micron/day, levonorgestrel-250 micron/day, "Nordial"-a combination of these two substances, and placebo. Affect was measured by the Hamilton Depression Rating Scale, verbal reports by women and self-ratings on visual analogue scales. Ethinyl oestradiol was found to have a beneficial influence on aspects of affect such as Hamilton scores, anxiety irritability and insomnia. The influence of hormones on Hamilton scores could be partly but not fully explained by the alleviation of hot flushes. Norgestrel showed less favourable changes initially but these tended to diminish by the third therapy month. Most of the women studied were not clinically depressed. Anxiety symptoms were the major features exhibited in the group of women investigated. The results of this study suggest that visual analogue rating scales are of questionable validity in assessing affect in patients without any appreciable psychiatric morbidity.
Affect↗