History Of Estrogen Therapy Research Articles

Misunderstood “menopausal” hormones: their controversy and complexity

No AccessMisunderstood “menopausal” hormones: their controversy and complexityBringing harmony to a bunch of misinterpreted hormones and to the women that flower our world Paulo de Valdoleiros Paulo de Valdoleiros1 https://orcid.org/0000-0002-7911-1293 Search for more papers by this author Affiliations 1Private practice, Cape Town, South Africa Published Online:1 Nov 2022https://doi.org/10.36303/SAGP.2022.3.5.0142https://hdl.handle.net/10520/ejc-mp_sagp_v3_n5_a5SectionsPDFView Full Text ToolsAdd to favouritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InRedditGMailOutlookYammermore AboutAbstractThis is the fourth article in the menopause series that began three South African GP editions ago. For the sake of continuity, it is recommended that you access the previous episodes if you missed them.1. Smith DCPrentice RThompson DJHerrmann WL "Association of exogenous estrogen and endometrial carcinoma" N Engl J Med1975 2932311647 DOI: https://doi.org/10.1056/NEJM197512042932302 Google Scholar2. Ziel HKFinkle WD "Increased risk of endometrial carcinoma among users of conjugated estrogens" N Engl J Med1975 29323116770 DOI: https://doi.org/10.1056/NEJM197512042932303 Google Scholar3. Kohn GERodriguez KMHotaling JPastuszak AW "The history of estrogen therapy" Sex Med Rev2019 7341621 DOI: https://doi.org/10.1016/j.sxmr.2019.03.006 Google Scholar4. WHOCancer fact sheetAvailable from: https://www.who.int/news-room/fact-sheets/detail/cancer#:~:text=The%20most%20common%20causes%20of,lung%20(1.80%20million%20deaths)%3B Google Scholar5. Stefanick ML "Estrogens and progestins: background and history, trends in use, and guidelines and regimens approved by the US Food and Drug Administration" Am J Med2005 118Suppl 12B6473 DOI: https://doi.org/10.1016/j.amjmed.2005.09.059 Google Scholar6. Horvath SSchreiber CASonalkar S "Contraception" Updated 2018 Jan 17Feingold KRAnawalt BBoyce Aet al.Endotext [Internet]South Dartmouth (MA) MDText.com, Inc.2000Table 2, Contraindications to Progestin-only Hormonal Contraceptives. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279148/table/contraception.progestino/ Google Scholar7. Czyzyk APodfigurna AGenazzani ARMeczekalski B "The role of progesterone therapy in early pregnancy: from physiological role to therapeutic utility" Gynecol Endocrinol2017 3364214 DOI: https://doi.org/10.1080/09513590.2017.1291615 Google Scholar8. Rossouw JEAnderson GLPrentice RLet al. "Writing Group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial" JAMA2002 288332133 DOI: https://doi.org/10.1001/jama.288.3.321 Google Scholar9. Viscoli CMBrass LMKernan WNet al. "A clinical trial of estrogen-replacement therapy after ischemic stroke" N Engl J Med2001 3451712439 DOI: https://doi.org/10.1056/NEJMoa010534 Google Scholar10. Manson JEChlebowski RTStefanick MLet al. "Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women’s Health Initiative randomized trials" JAMA2013 31013135368 DOI: https://doi.org/10.1001/jama.2013.278040 Google Scholar Previous article Next article FiguresReferencesRelatedDetails None Volume 3, Issue 5 | Nov 2022 Downloaded 1 times LanguagesEnglish InformationCopyright © 2022, Medpharm Publications:All rights reservedKeywordscardiovascularprogestinMIprogesteronemenopauseosteoporosisHRTestradiolstrokecancerPDF download Disclosure The authors confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. The authors confirm that they have given due consideration to the protection of intellectual property associated with this work and that there are no impediments to publication, including the timing of publication, with respect to intellectual property. Ethical conduct of research The authors state that they have obtained appropriate institutional review board outlined in the Declaration of Helsinki for all human or animal experimental investigations. A signed informed consent document has been obtained from all participants included in the study.

The History of Estrogen Therapy.

Menopausal hormone therapy (MHT) has proven an effective treatment for the amelioration of symptoms of menopause. The idea that a substance was the missing factor in a woman's body after menopause dates to the 1800s, when cow ovarian tissue was injected into German women in a successful attempt to reverse the sexual symptoms of menopause. The early 1900s saw the rise of commercialized menopause "treatments" that ranged in substance and even theoretical efficacy. The role of estrogen was first accurately described in Guinea pigs in 1917 by Dr. Papanicolaou. To tell the detailed history of how estrogen was discovered and the controversy surrounding MHT. A literature search was conducted using PubMed to identify relevant studies and historical documents regarding the history of estrogen therapy. The history of estrogen supplementation and its controversies are interesting stories and relevant to today's ongoing investigation into hormone replacement. The controversy of MHT remained until the first randomized trials examining MHT in the early 1990s that suggested MHT is cardioprotective in postmenopausal women, although this conclusion was contradicted in subsequent trials. In the present day, MHT is approved only for short-term use for the symptomatic treatment of menopause. Kohn GE, Rodriguez KM, Hotaling J, etal. The History of Estrogen Therapy. Sex Med Rev 2019;7:416-421.

Dietary habits contributing to breast cancer risk among Iranian women.

The aim of this study was to investigate demographic features, dietary habits, and some possible risk factors for being susceptible to breast cancer in Iranian women. A study of dietary habits and breast cancer was conducted among 53 Iranian women with histological confirmed disease and 40 matched controls. A dietary habits questionnaire was used to evaluate the pattern of selected food intakes. The risk of cancer was analyzed after adjustment for confounding factors. Age, weight, body mass index (BMI), waist circumference, educational status, parity, lactation, marital status, menopause, history of estrogen therapy, and family history of breast disease or cancer were assessed among participants. Special attention was given to the relationship between consumption of high fat meat, milk, yogurt and cheese as well use of frying oils for frying foods, use of olive/liquid oils for cooking, removing fat from meat and poultry, removing chicken skin and not use of mayonnaise as salad dressing and the risk of breast cancer. Moreover, salad, vegetable and fruit consumption, and eating outdoors owere investigated. Our results revealed significant lower education and higher BMI and waist circumference levels in patients with breast cancer. There was significantly increased breast cancer risk in overweight women in comparison with normal weight (OR=2.91, 95%CI 1.24 to 6.82). High intake of fat dairy products including milk and cheese was found to be a statistically significant factor for increasing breast cancer risk in models adjusting for age, BMI and education. Use of olive/liquid oils for cooking and avoidance of mayonnaise as salad dressing are related to lower risk of breast cancer. The frequency of vegetable and fruit consumption was significantly lower in patients with breast cancer compared to healthy women. Dietary habits might be risk factors for breast cancer among Iranian women. Adoption of a prudent diet could be an appropriate strategy for preventing breast cancer.

Synchronous bilateral breast cancer in a male patient following hormone therapy for prostate cancer

We report an unusual case of bilateral, synchronous breast cancer in a male patient who had a history of estrogen therapy for prostate cancer. A 64-year-old Japanese man was diagnosed with T1N0M0 prostate cancer and received a total prostatectomy. Twenty months after the resection, the patient developed multiple bone metastases, and received radiation therapy, systemic chemotherapy, and hormone therapy for 15 months. After completing this treatment, he was diagnosed with T1N0M0 primary breast cancer in his left breast and underwent a modified mastectomy. Five months after the mastectomy he received systemic chemotherapy followed by estrogen therapy because of the progression of prostate cancer. Three months after this treatment, he was diagnosed with T1N0M0 primary breast cancer in his right breast. To the best of our knowledge, this is a rare case of synchronous bilateral male breast cancer following hormone therapy for prostate cancer.

Mixed epithelial and stromal tumor of the kidney and cystic nephroma share overlapping features: reappraisal of 15 lesions.

Abstract Context.—Cystic nephroma is a rare cystic tumor, which only recently has been recognized as an exclusively adult lesion. Mixed epithelial and stromal tumor of the kidney is also a rare, recently recognized, biphasic tumor composed of tubular and cystic elements embedded in grossly recognizable spindle cell stroma. The histogenesis of both lesions is unclear. Objectives.—To compare clinical phenotype, morphology, and immunohistochemistry in mixed epithelial and stromal tumor of the kidney and cystic nephroma in order to explore the relationship between these 2 lesions. Design.—Fifteen biphasic lesions (8 mixed epithelial and stromal tumors of the kidney and 7 cystic nephromas) were studied. All cases were reviewed and subjected to detailed pathologic studies, and the results were correlated with clinical findings. Results.—Mixed epithelial and stromal tumor of the kidney occurred exclusively in women aged 36 to 80 years (mean, 49.7 years), all of whom had a history of estrogen therapy and/or obesi...

Mixed Epithelial and Stromal Tumor of the Kidney and Cystic Nephroma Share Overlapping Features: Reappraisal of 15 Lesions

Cystic nephroma is a rare cystic tumor, which only recently has been recognized as an exclusively adult lesion. Mixed epithelial and stromal tumor of the kidney is also a rare, recently recognized, biphasic tumor composed of tubular and cystic elements embedded in grossly recognizable spindle cell stroma. The histogenesis of both lesions is unclear. To compare clinical phenotype, morphology, and immunohistochemistry in mixed epithelial and stromal tumor of the kidney and cystic nephroma in order to explore the relationship between these 2 lesions. Fifteen biphasic lesions (8 mixed epithelial and stromal tumors of the kidney and 7 cystic nephromas) were studied. All cases were reviewed and subjected to detailed pathologic studies, and the results were correlated with clinical findings. Mixed epithelial and stromal tumor of the kidney occurred exclusively in women aged 36 to 80 years (mean, 49.7 years), all of whom had a history of estrogen therapy and/or obesity. Cystic nephroma occurred in both sexes; patients were aged 22 to 71 years (mean, 50.4 years), and a history of hormonal therapy was present on occasion. All 15 lesions were benign. Lesions varied by size, the proportion of cystic component, and the amount and cellularity of stroma. However, in all lesions tested, the stroma was diffusely positive for smooth muscle actin, and smooth muscle differentiation was confirmed by electron microscopy. In mixed epithelial and stromal tumors of the kidney, the stroma was positive for estrogen and progesterone receptors in 4 of 5 lesions tested. In cystic nephroma, focal positivity for hormone receptors was seen in 2 of 7 tumors tested; both positive lesions were from women. The epithelial lining in both mixed epithelial and stromal tumor of the kidney and cystic nephroma lesions was variable with regard to shape, cytoplasmic appearance, and immunophenotype (with focal positivity for CD10, cytokeratin 7, high-molecular-weight keratin, and Ulex europaeus detectable in both lesions). This pattern suggests variable differentiation, which was confirmed by electron microscopic studies (performed in 1 case). While mixed epithelial and stromal tumor of the kidney has a strong association with the female sex and hormonal milieu, cystic nephroma can affect both sexes and, on occasion, may also have hormonal associations. Morphologically, there is considerable overlap between both lesions, which suggests that they may represent opposite ends of the spectrum of the same process. Our studies also suggest that the tubules may be entrapped rather than comprising an intrinsic component of the tumor. However, further studies, including molecular studies, are needed to support this hypothesis.

Effect of Soy Protein Containing Isoflavones on Cognitive Function, Bone Mineral Density, and Plasma Lipids in Postmenopausal Women: A Randomized, Controlled Trial

Declining estrogen levels at menopause are accompanied by deteriorating cognitive function. Postmenopausal estrogen therapy might counteract this and other perimenopausal changes such as increasing plasma lipid levels and decreasing bone mineral density (BMD). Even short-term estrogen therapy, however, may cause recurrent vaginal bleeding, and long-term replacement has been related to increased risks of breast cancer, cardiovascular disease, and stroke. Phytoestrogens such as isoflavones and lignans are estrogen-like compounds found in plant foods that activate estrogen receptors and, in the postmenopausal state, may act as agonists. The investigators sought to determine the effects of supplemental soy protein, which contains the isoflavones genistein and daidzein, on cognitive function, BMD, and plasma lipids. A double-blind, randomized, placebo-controlled trial enrolled 202 healthy postmenopausal women 60 to 75 years of age, who were randomized to receive 25.6 g of soy protein containing 99 mg of isoflavones in powder form or a placebo each day for 12 months. In addition to the Mini-Mental State Examination, participants were evaluated by short- and long-term tests of verbal and visual memory and measures of naming and verbal fluency. BMD was estimated at the hip and lumbar spine by dual-energy x-ray absorptiometry. Baseline cognitive performance was similar in the study and control groups. Women given soy did slightly better on most tests of memory, but the differences were not statistically significant or clinically meaningful. Tests of verbal skills, concentration, and visual attention showed no significant between-group differences. Comparable results were obtained after excluding women who were depressed. The findings were not influenced by years since menopause, body mass index, smoking status, or history of estrogen therapy. BMD declined in both groups after 12 months. Plasma levels of low-density lipoprotein cholesterol and total cholesterol did not change in the soy group and decreased slightly in the placebo group. The findings of this randomized trial fail to support the possibility that isoflavones in soy protein have beneficial effects on cognitive function, BMD, or plasma lipids in healthy postmenopausal women aged 60 and older.

A Predictive Model for the Development of Hormone-Responsive Breast Cancer

Effective therapies to reduce the risk of hormone-sensitive breast cancers (ER or PR positive) exist. Available models predict the risk of breast cancer without addressing hormone receptor status. The purpose of this study was to identify risk factors predictive of the development of hormone-sensitive cancers. A total of 1285 invasive breast cancers in 1263 women were identified from a prospectively maintained database. Risk factors were compared for ER+ and ER- cancers by using Fisher's exact test. Models were developed for premenopausal and postmenopausal women. In premenopausal women, white race, age at menarche < 12 years, and nulliparity or age at first birth > 20 years were used. The risk of ER+ cancer increased from 67.7% with 0 variables to 83.8% with all three (P = .013). In postmenopausal women, white race and a history of estrogen therapy were used. With none of the variables present, the incidence of ER+ cancer was 70.0%; it was 77.6% with one variable and 85.4% with both variables (P = .002). In postmenopausal women, variables predicted significant differences in hormone sensitivity only for those aged < or = 60 years. In the subset of women with information on alcohol use, adding this variable to the model improved the prediction of hormonal status. Our findings, if prospectively validated, may help identify those who would obtain the greatest benefit from hormonal chemoprevention strategies for breast cancer risk reduction.

P53 gene mutations and protein accumulation in human ovarian cancer.

Mutations of the p53 gene on chromosome 17p are a common genetic change in the malignant progression of many cancers. We have analyzed 38 malignant tumors of ovarian or peritoneal müllerian type for evidence of p53 variations at either the DNA or protein levels. Genetic studies were based on single-strand conformation polymorphism analysis and DNA sequencing of exons 2 through 11 of the p53 gene; mutations were detected in 79% of the tumors. These data show a statistically significant association between mutations at C.G pairs and a history of estrogen therapy. Two of 20 patients whose normal tissue could be studied carried germ-line mutations of p53. Immunohistochemical analysis of the p53 protein was carried out using monoclonal antibody PAb1801. Ninety-six percent of the missense mutations were associated with abnormal accumulation of p53 protein, but nonsense mutations, a splicing mutation, and most deletions did not result in p53 protein accumulation. A statistically significant association between p53 protein accumulation in poorly differentiated stage III serous carcinomas and small primary tumor size at diagnosis was found, perhaps suggesting that p53 protein accumulation accelerates the metastatic spread from a primary tumor. Overall, our findings indicate that alterations of p53 play a major role in ovarian cancer, including predisposition to the disease in some patients, and suggest a possible mechanism for somatic mutations leading to this cancer.

Morphologic Correlates of Host Response in Endometrial Carcinoma*

Cases of endometrial carcinoma reviewed for this study were divided into two groups: 1) Premenopausal, perimenopausal and postmenopausal patients in whom a history of anovulation, obesity, ovarian hyperthecosis (including Stein-Leventhal syndrome) or feminizing tumors, and/or exogenous estrogen intake were found; and 2) post menopausal, elderly patients, without known hormonal or metabolic disturbances and without any history of estrogen therapy. In the first group, frequent associated findings were precursor stages of endometrial carcinoma, such as adenomatous and atypical hyperplasia. In the majority of cases, the cancer was confined to the endometrium, rarely infiltrating the myometrium. In the second group, the cancer was associated most often with an inactive, atrophic endometrium and frequently diffusely infiltrated through the myometrium, with lymphatic and vascular involvement. The lymphatic and plasma-cell infiltrate was evaluated in both groups. It was found to be more abundant in the first group, but at the tumor-host interface and perivascularly, than in the second. As reported in other malignancies of the female reproductive system, the presence or absence of a lymphocytic infiltrate as a morphological expression of local cellular immune response of the host correlates well with the biological behavior of the tumor. A challenging question is the relationship, if any, between hormonal factors and immune mechanisms in tumors arising in tissues such as the endometrium that, even normally, are targets of hormonal stimulation.

Estrogens and Menopause

RECENT reports suggest that the administration of estrogens to postmenopausal women is associated with an increased risk of acquiring endometrial cancer. The problem was identified in retrospective studies in which postmenopausal patients with endometrial cancer were compared to matched controls with respect to their history of estrogen therapy. Ziel and Finkle¹compared 94 endometrial cancer patients with 188 controls from the same health plan who were matched on the basis of age, area of residence, and length of time in the health plan. The estimated risk of acquiring endometrial cancer was 7.6 times higher for women who were treated with estrogens, and the risk increased with the length of time on the medication. The estimated risk increased from 5.6 times for 1 to 4.9 years of use to 13.9 times for seven or more years of use. Smith et al²compared women with endometrial cancer to women with