Estrogen Hormone Replacement Therapy Research Articles

Hormone replacement therapy did not alleviate temporomandibular joint inflammatory pain in ovariectomized rats.

This study had the aim of examining the relationships between variations in estrogen levels resulting from ovariectomy, and estrogen hormone replacement therapy (HRT) in rats subjected to an orofacial inflammatory pain model. Eighty adult female Wistar rats were initially divided into 2 groups: Sham or ovariectomy (OVX-D1). Seven days later (D7), the rats were subjected to an unilateral infiltration of Freund's Complete Adjuvant (CFA) or saline solution into the right temporomandibular joint (TMJ). Then, rats received 17β-estradiol (28µg/kg/day) or placebo for 21days (D10-D31). Nociception was evaluated by the von Frey (VF) and the Hot Plate (HP) tests, and depressive-like behavior by the Forced Swimming (FS) test. On D32 all rats were euthanized and serum, hippocampus and brainstem were collected. The CFA groups presented a mechanical hyperalgesia until day 21 (p ≤ 0.05). No differences were observed among groups in the HP (p = 0.735), and in the immobility and swimming time of the FS (p = 0.800; p = 0.998, respectively). In the brainstem, there was a significant difference in the TNF-ɑ levels (p = 0.043), and a marginal significant difference in BDNF levels (p = 0.054), without differences among groups in the hippocampal BDNF and TNF-ɑ levels (p = 0.232; p = 0.081, respectively). In conclusion, the hormone replacement therapy did not alleviate orofacial pain in ovariectomized rats. However, there is a decrease in brainstem TNF-ɑ levels in the animals submitted to both models, which was partially reverted by HRT.

Prolame produces anxiolytic- and antidepressant-like effects in middle-aged female rats with less uterotrophic effects than 17β-estradiol

Estrogen hormone replacement therapy (EHRT), improving women's life quality at menopause, reduces anxiety and depression symptoms associated with ovarian hormonal decline. However, its potential adverse effects, like thromboembolism and cancer risk, limit its use. Prolame is a synthetic 17β-amino estrogen with antithrombotic actions that exerts anxiolytic- and antidepressant-like effects on young adult ovariectomized female rats. It is unknown if prolame's effects may be observed in age and endocrine conditions emulating menopause. This study aimed to identify the antidepressant- and anxiolytic-like effects of prolame and E2 (used as a reference estrogen treatment) in middle-aged female rats coursing with irregular cycles, in two different conditions: ovariectomized or gonadally intact. Results were compared with those from young adult ovariectomized rats. Prolame (60 or 120 μg/kg), 17β-estradiol (E2, 40 or 80 μg/kg), or vehicle were chronically administered, and their effects were evaluated in the elevated plus-maze, defensive burying behavior test, open field test, and forced swimming test. Uterotrophic actions were estimated by uterine weight related to body weight. Prolame and E2 produced robust anxiolytic- and antidepressant-like effects in young adult ovariectomized rats, but these effects were absent in gonadally intact middle-aged rats. Interestingly, only prolame induced anxiolytic- and antidepressant-like effects in middle-aged ovariectomized rats. Uterotrophic effects of prolame were weaker than E2 effects, notably in middle-aged females. Altogether, present data support the notion that prolame has the potential to be considered an EHRT with relevant psychoactive actions and with apparently lower adverse-side effects, especially in middle-aged populations.

Lamotrigine and exogenous estrogen among females with epilepsy: A retrospective analysis of administrative claims data

ObjectiveExogenous estrogen reduces lamotrigine serum concentrations. Little is known about whether providers adjust lamotrigine doses for addition of exogenous estrogen among people with epilepsy, despite expert recommendations. We determined the incidence of dose increases in lamotrigine following incident prescription of estrogen among females with epilepsy (FWE) in claims data. MethodsWe used Optum’s de-identified Clinformatics® Data Mart Database to create a cohort of U.S. FWE prescribed lamotrigine at a stable dose, with a subsequent prescription for estrogen from 2011 to 2021. We calculated cumulative incidence functions of dose increases in lamotrigine following prescription of exogenous estrogen. We performed a Cox proportional hazards model for multiple candidate predictors of a lamotrigine dose increase. ResultsThe cohort included 643 FWE, with median age of 31 (interquartile ratio [IQR] 20–42). The cumulative incidence of any lamotrigine increase was 28% (95% confidence interval [CI] 25%–32%). The median number of days after the first estrogen fill until the first lamotrigine adjustment was 118 (IQR 48–188). In unadjusted Cox models, older age, use of estrogen in hormone replacement therapy as opposed to contraception, and annual household income of $50,000-$99,999 (compared with <$50,000) were significant negative predictors of a dose adjustment in lamotrigine with hazard ratios (HRs) of 0.82 (95% CI 0.72–0.92), 0.63 (95% CI 0.42–0.95), and 0.62 (95% CI 0.40–0.95). In the adjusted Cox model, age and income remained significant predictors with HRs of 0.79 (95% CI 0.66–0.94) and 0.59 (95% CI 0.36–0.95). ConclusionDose increase of lamotrigine following addition of exogenous estrogen is rare among U.S. FWE, with potential disparities based on age and income level. More guidance may be needed for providers on this topic.

Herbal Remedies for Osteoporosis

Osteoporosis is a widespread concern that poses significant health risks. In the past, it was commonly thought that women would naturally undergo this condition as they age, especially during menopause when hormonal imbalances heighten the risk. Osteoporotic fractures affect approximately one in three women and one in five men over the age of 50 during their lifetimes. The mature skeleton constantly undergoes a remodelling process that involves both bone formation and resorption. However, when bone resorption exceeds bone growth, osteoporosis develops. Both men and women need to prioritize their bone health throughout their lives. Addressing factors that impact bone health at every stage becomes crucial in preventing osteoporosis. To combat the rising incidence of osteoporotic fractures, it is crucial to implement effective preventive measures aimed at maximizing peak bone density, limiting accelerated bone loss, and reducing the risk of falls. Present therapy goals primarily focus on stopping further bone loss and fractures, preserving bone mass, and utilizing medications like bisphosphonates, Selective Estrogen Receptor Modulators (SERMs), anabolic steroids, strontium, and Hormonal Replacement Therapy (HRT). However, it’s worth noting that some of these treatments, such as HRT, bisphosphonates, SERMs, and anabolic steroids, may have negative side effects. As a result, there is an urgent need to identify effective, affordable, natural, and less harmful compounds to manage osteopenia/osteoporosis effectively. The search for safer alternatives is crucial in combating this condition and promoting better bone health.

A Case of Turner Syndrome Presenting as Aneurysmal Subarachnoid Hemorrhage

We report a rare case of cerebral aneurysmal subarachnoid hemorrhage (SAH) associated with Turner syndrome. A 34-year-old woman presented with aneurysmal SAH originating from a saccular aneurysm in the right anterior communicating artery. The patient underwent endovascular coil embolization of the aneurysm. The patient recovered favorably after surgery without any neurological deficits. She had previously been diagnosed with Turner syndrome, which was managed with medical treatment, including estrogen hormone replacement therapy. It is uncommon for a patient with Turner syndrome to present with aneurysmal SAH; nonetheless, aneurysmal SAH could be a clinical concern. Further investigations are needed to reveal the risk factors, vascular anatomy, and causative mechanisms of aneurysmal SAH in patients with Turner syndrome.

The Correlation Between Progesterone and Mammographic Density in Postmenopausal Women: A Systematic Review of the Literature and Meta-Analysis.

Higher mammographic breast density in premenopausal and postmenopausal women is related to a higher breast cancer risk. In this review, we analyze the correlation between estrogen, progesterone, and mammographic density in postmenopausal women and clarify whether these findings are consistent across different types of mammographic breast density. We extracted data concerning mammographic density increases in the populations treated with estrogen-only hormone replacement therapy and those treated with estrogen and progestin hormone replacement therapy. Postmenopausal women treated with estrogen and progesterone regimens had a statistically significant lesser mammographic density increase than estrogen-only hormone replacement therapy regimens.

(105) The Discovery of New Incredible Positive Actions of Hormone Replacement Therapy and Sex in Menopause

Abstract Introduction Every year, two or more benefits of the use of hormone replacement therapy (HRT) in menopause and andropause appear in medical literature. We present an extensive review of the literature describing the classical and novel benefits of hormonal replacement therapy and sex in menopause. Additionally, we present recent findings from our own patient population. Objective To contribute to the presently known benefits of the use of HRTs, and additionally to present new findings from our own practice not previously described. Methods We conducted an extensive literature review and described our own experience and findings within our centers. Results `- In the area of prevention and treatment of genitourinary syndrome of menopause, we have found: - Prevention and treatment of false positive cervical dysplasia in perimenopause. - Prevention and treatment of vulvar, labial, and vaginal occlusion in late menopause. - Prevention and treatment of recurrent urinary tract infections in geriatric patients for prevention of sepsis, secondary pneumonia, and even death. - Prevention and treatment of clitoral atrophy, phimosis, and urethral caruncles - Dermatology: We have found: - Prevention and treatment of wrinkles, alopecia related, postmenopause. - Prevention in prostrated geriatric patients of decubitus ulcers. - Internal Medicine: prevention of obesity, decreased metabolic rate, and insulin resistance. - Ophthalmology: - Prevention and treatment of macular degeneration. - Prevention of glaucoma (increased intraocular pressure), most notably in primary open- angle glaucoma. - The prevention of aging of optic nerve and neuroprotection of retinal cells. - Oncology: - Prevention of kidney cancers, and breast cancer (only estrogen hormone replacement therapy). - Enhanced visualization of the transformation zone during cervical cancer screening - Gastroenterology: protection of the gut microbiome and serum metabolome, especially in premature ovarian insufficiency - Dentistry: prevention of tooth loss through decreased gingival inflammation and periodontitis, mandibular bone loss, and oral dysesthesia. - Neurology: - Protection against intracranial aneurysm rupture in ovariectomized mice. - The prevention of Parkinson’s and Alzheimer’s disease - Rheumatology: prevention of rheumatoid arthritis. Conclusions To demonstrate the number of studies with the anti-aging mechanism of the use of HRT. How this knowledge, alongside our own findings of hundreds of menopausal women within our centers justify the generalized use of this therapy. Disclosure No

Hormone replacement therapy and COVID-19 outcomes in solid organ transplant recipients compared with the general population

Exogenous estrogen is associated with reduced coronavirus disease (COVID) mortality in nonimmunosuppressed/immunocompromised (non-ISC) postmenopausal females. Here, we examined the association of estrogen or testosterone hormone replacement therapy (HRT) with COVID outcomes in solid organ transplant recipients (SOTRs) compared to non-ISC individuals, given known differences in sex-based risk in these populations. SOTRs ≥45 years old with COVID-19 between April 1, 2020 and July 31, 2022 were identified using the National COVID Cohort Collaborative. The association of HRT use in the last 24 months (exogenous systemic estrogens for females; testosterone for males) with major adverse renal or cardiac events in the 90 days post-COVID diagnosis and other secondary outcomes were examined using multivariable Cox proportional hazards models and logistic regression. We repeated these analyses in a non-ISC control group for comparison. Our study included 1135 SOTRs and 43 383 immunocompetent patients on HRT with COVID-19. In non-ISC, HRT use was associated with lower risk of major adverse renal or cardiac events (adjusted hazard ratio [aHR], 0.61; 95% confidence interval [CI], 0.57-0.65 for females; aHR, 0.70; 95% CI, 0.65-0.77 for males) and all secondary outcomes. In SOTR, HRT reduced the risk of acute kidney injury (aHR, 0.79; 95% CI, 0.63-0.98) and mortality (aHR, 0.49; 95% CI, 0.28-0.85) in males with COVID but not in females. The potentially modifying effects of immunosuppression on the benefits of HRT requires further investigation.

Modulation of vulvovaginal atrophy (VVA) by Gelam honey in bilateral oophorectomized rats.

Vulvovaginal atrophy (VVA) is a common condition in post-menopausal women. Symptoms of VVA include dyspareunia, vaginal dryness, vaginal and/or vulvar itching, burning and soreness, dysuria and vaginal bleeding accompanying sexual activity. These symptoms are physiological responses to hypoestrogenicity, inducing atrophy of the vagina epithelia and sudden reduction in mucous production. Prevailing therapy for VVA is hormone replacement therapy (HRT), notably estrogen, progesterone or a combination of the two. However, using HRT is associated with an increased incidence of breast and endometrial cancer, venous thromboembolism in the lungs and legs, stroke and cardiovascular complications. This study evaluated Malaysian Gelam honey as a nutraceutical alternative to estrogen HRT (ERT) in alleviating VVA. A total of 24 female 8-weekold Sprague Dawley rats underwent bilateral oophorectomy. A minimum of 14 days elapsed from the time of surgery and administration of the first dose of Gelam honey to allow the female hormones to subside to a stable baseline and complete recovery from surgery. Vaginal tissues were harvested following a 2-week administration of Gelam honey, the harvested vagina tissue underwent immunohistochemistry (IHC) analysis for protein localization and qPCR for mRNA expression analysis. Results indicated that Gelam honey administration had increased the localization of Aqp1, Aqp5, CFTR and Muc1 proteins in vaginal tissue compared to the menopause group. The effect of Gelam honey on the protein expressions is summarized as Aqp1>CFTR>Aqp5>Muc1. Gene expression analysis reveals Gelam honey had no effect on Aqp1 and CFTR genes. Gelam honey had up-regulated Aqp5 gene expression. However, its expression was lower than in the ERT+Ovx group. Additionally, Gelam honey up-regulated Muc1 in the vagina, with an expression level higher than those observed either in the ERT+Ovx or SC groups. Gelam honey exhibits a weak estrogenic effect on the genes and proteins responsible for regulating water in the vaginal tissue (Aqp1, Aqp5 and CFTR). In contrast, Gelam honey exhibits a strong estrogenic ability in influencing gene and protein expression for the sialic acid Muc1. Muc1 is associated with mucous production at the vaginal epithelial layer. In conclusion, the protein and gene expression changes in the vagina by Gelam honey had reduced the occurrence of vaginal atrophy in surgically-induced menopause models.

An Improved Method for Assessing Macroscale Diffusion Through Osteonal Bone.

The characterization of diffusion through biological tissues has played an important role in fundamental medical research and product development. Understanding the diffusion phenomena allows for the identification of new concepts in fundamental science, evolving medical knowledge and improving future standards and protocols. To illustrate, the structure of cortical bone changes upon the onset of osteoporosis, altering the limited porous compartment through which nutrients and essential signaling molecules travel to bone cells. Estrogen hormone replacement therapy (HRT) is one of the gold standard treatments to attempt to mitigate the effects that this structural change exerts in menopausal osteoporosis patients; however, HRT effectiveness is often variable in these patients, likely due to variability in bone structure and physiology, and thus transport rates. Scientists have studied diffusion in cortical bone tissue for decades. Current methodological standards include fluorescence recovery after photobleaching and computed tomography finite element analysis. Both techniques limit areas of tissue to microscale (1-100 μm2) analysis-only examining a few osteocytes within the structure at a time-and adopt assumptions that oversimplify in vivo tissue structure and transport phenomena. Also, the range of diffusion tracers is limited by the sensitivities of the analytical equipment, typically requiring tracer concentrations in the micromolar range. Herein is described a novel device for directly assessing the diffusion coefficient of 3H-estradiol at 37°C in macroscale osteonal bone specimens (1.4 cm2)-assessing a much larger portion of the total tissue than previously reported-while using radioisotope tracers for much higher sensitivity, thus achieving physiologically relevant estradiol concentrations. The current diffusion chamber device represents a cost-effective and validated method to mitigate these shortcomings. The device provides long-term diffusion data through macroscale (greater than 1 mm2) tissue areas, presenting a more physiologically accurate way to assess cortical bone diffusion. The device can assess solute diffusion through other tissues or materials and may easily be scaled up to run multiple diffusion experiments simultaneously. Impact statement The diffusion chamber device represents a cost-effective and validated method to assess solute diffusion through solid materials. Specifically, it demonstrates that this novel device provides long-term diffusion data through macroscale tissue samples at nanomolar concentrations, presenting a precise way to address the effects of tissue structures on diffusion. This device can be applied to other tissues or engineered materials, offering a methodology that is easily scaled up to allow simultaneous assessment of multiple material samples.

Liver Abnormalities in Turner Syndrome: The Importance of Estrogen Replacement.

Turner syndrome is one of the most frequently reported sex chromosomal abnormalities, affecting approximately 40 in every 100 000 live female births. The underlying chromosomal alteration is the complete or partial loss of X chromosome or mosaicism. Because of primary ovarian insufficiency, the synthesis of estrogen hormones is compromised, and patients require hormone substitution. Apart from the phenotypical presentation (short stature, primary amenorrhea), the effects of ovarian insufficiency can affect diverse organ systems (such as cardiovascular, endocrine, and lymphatic systems). Hepatobiliary pathology can present on a broad spectrum: from mild asymptomatic hypertransaminasemia to marked architectural changes. Estrogen hormone replacement therapy in these patients can improve the perturbations of laboratory values and can attenuate the progression of hepatic structural changes. Moreover, providing sufficient estrogen replacement has numerous benefits for other conditions of the patients as well. Both the all-cause mortality and deaths from cardiovascular complications are greatly increased in Turner syndrome, and hormone replacement might contribute to the decreased incidence of these events. The diagnostics of Turner syndrome are outside the scope of our paper, and we briefly discuss the cardiovascular complications because many the liver involvement partially involves alterations of vascular origin. Though we sought to highlight the importance of proper hormone replacement therapy, we did not attempt to write a comprehensive recommendation for exact treatment protocols. We provided an overview of preferred therapeutic approaches, as the treatment should be tailored according to the individual patient’s needs.

What is the association between estrogen and breast cancer?

Aim: There is a historical acceptance about the causal relationship between Estrogens and Breast cancer which has either affected the incidence rate or mortality rate of breast cancer, or could have influenced the uptake or continuation of Estrogen in Hormone Replacement Therapy (HRT). Estrogens are useful either as Estrogen-only HRT (ERT) or as combined Estrogen and Progestogen HRT. There is now a need to clearly differentiate between ERT and HRT in their consequences with regard to breast cancer. This review documents the basis of the historical causal connection and the current situation Methodology: The literature was searched with the following key words: Estrogen, Breast cancer, Estrogen receptors and Menopause;. Incidence and mortality rates of breast cancer associated with Estrogen. Randomized controlled Trials, Observational studies. Cell proliferation, cell differentiation and cell development. Results: The relationship between Estrogen &amp; Breast Cancer with regard to incidence and mortality requires a rigorous scrutiny because: There are prenatal influences which have an impact on exposure to Xenoestrogens across the life course, starting with conception – if not before, giving possible effects on germ cells and gametes. The evidence from observational studies should be interpreted with caution because of procedural inadequacies. The evidence that should be used for care of women is that from Randomised controlled trials because they are geared to infer on cause and effect relationships. The relationship between Estrogen alone for peri-menopause and menopause shows that it does not increase the risk of breast cancer or the mortality from breast cancer. Conclusion: Estrogen alone does not increase the risk and the mortality of breast cancer. The combination of ERT with a progestogen can increase the risk of breast cancer.

Differential Genomic Interactions Drive Progesterone Receptor Isoform Specific Functions in Breast Cancer

Progesterone is critical for normal breast development and function, and has been shown to stimulate proliferation of normal breast epithelial cells by increasing stem and progenitor cell numbers. Breast cancer incidence is increased in women exposed to progesterone analogues in combined estrogen plus progestin hormone replacement therapy, but not in women taking estrogen alone. Classical progesterone signaling is mediated through the nuclear progesterone receptor (PR), which occurs as two related but functionally different isoforms, PRA and PRB. PRA and PRB are co-expressed equally in normal breast tissue but become dysregulated in breast cancer where PRA often becomes predominant. PRA predominance in breast cancer is associated with poorer outcome and higher risk of distant metastasis in tamoxifen treated patients. We show using integrated analysis of ChIP-seq, ATAC-seq and transcriptomic profiling in a breast cancer cell line model of acquired PRA predominance that: 1) PRA and PRB have different requirements with regard to chromatin accessibility; 2) PRA predominance reshapes the PR cistrome and the associated transcriptome to affect genes not normally regulated by PR when PRA and PRB are equivalently expressed, possibly through assisted loading with multiple other transcription factors; 3) Genes regulated by PR only when PRA is predominant are associated with poorer breast cancer outcome and involved in multiple cancer-associated pathways including those that regulate cell proliferation and adhesion. Our data suggest a mechanism for the poorer disease outcome seen in breast cancers with a predominance of PRA.

Estrogen hormone replacement therapy in incidental intracranial meningioma: a growth-rate analysis

Incidental meningiomas (IMs) are the most common intracranial neoplasms, especially in perimenopausal women. There is ongoing debate on whether their incidence is increased by hormone replacement therapy. Meningiomas often express estrogen receptors, which were linked to higher proliferative activity according to some reports. Consequently, there is a theoretical risk of estrogen-based HRT (e-HRT) leading to an increase in tumor growth and thus altering the natural history of IMs. However, clinical data is lacking to support this notion. To identify differences in the natural history of IM after e-HRT exposure. We queried the NorthShore Meningioma Database for patients with ≥ 6 months of e-HRT. They were compared with age-matched IM controls. Forty patients were included in the e-HRT group (mean age 62.1 ± 12.0 years; mean duration of HRT 5.3 ± 4.5 years) and 80 in the no-HRT group (mean age 62.2 ± 12 years). Radiographic appearance was similar between groups. The average 2D tumor diameter was 35% lower in the e-HRT group (p = 0.02), with an absolute growth-rate of half of the no-HRT group (p = 0.02). Radiographic and clinical progression-free survival were 1.2 years and 3.3 years longer in the e-HRT group, respectively. These preliminary results suggest that e-HRT may be safe in incidental meningiomas.

Chronic Pelvic Pain Caused by Postmenopausal Endometriosis

This study was deemed exempt by the Institutional Review Board and did not require its approval. A 38-year-old woman presented with chronic pelvic pain. She reported an extensive surgical history focused primarily on treatment of endometriosis of unknown stage and pelvic pain. This included total hysterectomy and bilateral salpingectomy subsequently followed by bilateral oophorectomy 3 years previously. After her surgical menopause, she underwent 6 additional robotically assisted procedures during a 3-year period, which involved fulguration of endometriosis. She denied having had any previous excisional procedures performed. The possibility of an ovarian remnant could not be ascertained at the time of initial presentation secondary to exogenous estradiol being used for hormone replacement therapy. Given the patient's extensive history of endometriosis treatment, persistent symptoms, and lack of previous excision, the decision was made to proceed with surgical evaluation and treatment. Any endometriosis encountered would be excised, and assessment for ovarian remnant would be performed. Intraoperative evaluation revealed multiple areas visually suspicious for endometriosis (Fig. 1, Fig. 2). All areas of concern for endometriosis were excised and a full pelvic peritonectomy was performed. The infundibulopelvic ligaments were identified, relegated at their origins, and excised to ensure no residual ovarian tissue was left in situ (Fig. 3). Pathology confirmed the presence of endometriosis and no ovarian remnant.Fig. 2Fibrosis and lesions visually consistent with endometriosis involving the left abdominal wall. Evidence of previous left salpingo-oophorectomy present.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Fig. 3Pelvis after completion of excision of endometriosis, pelvic peritonectomy and removal of infundibulopelvic ligaments bilaterally.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Postoperatively, the patient was continued on estrogen hormone replacement therapy to decrease overall morbidity and mortality. She reported rapid improvement in pain for several months. With increased activity, the patient experienced new onset of periumbilical pain. Physical examination revealed myofascial dysfunction resulting in pain in the pelvic floor and abdominal wall. Pelvic floor physical therapy and cyclobenzaprine were recommended and resulted in further improvement in her pain. Endometriosis is diagnosed in the menopausal time frame in 2%–5% of all cases [1Oxholm D Knudsen UB Kryger-Baggesen N Ravn P Postmenopausal endometriosis.Acta Obstet Gynecol. 2007; 86: 1158-1164Crossref PubMed Scopus (44) Google Scholar]. In women with previous hysterectomy and bilateral salpingo-oophorectomy, 8.3% required a subsequent surgery within 7 years [2Shakiba K Bena JF McGill KM Minger J Falcone T Surgical treatment of endometriosis: a 7-year follow-up on the requirement for further surgery.Obstet Gynecol. 2008; 111: 1285-1292Crossref PubMed Scopus (171) Google Scholar]. Although endometriosis in menopausal patients can be stimulated by hormone replacement therapy, this disease process has also been noted in patients without any exogenous hormone administration. [1Oxholm D Knudsen UB Kryger-Baggesen N Ravn P Postmenopausal endometriosis.Acta Obstet Gynecol. 2007; 86: 1158-1164Crossref PubMed Scopus (44) Google Scholar]. Medical therapy options for treatment of menopausal endometriosis are limited because of natural changes in the hypothalamic-pituitary-ovarian pathway in this population [2Shakiba K Bena JF McGill KM Minger J Falcone T Surgical treatment of endometriosis: a 7-year follow-up on the requirement for further surgery.Obstet Gynecol. 2008; 111: 1285-1292Crossref PubMed Scopus (171) Google Scholar]. Specifically, aromatase inhibitors can be effective, whereas gonadotropin-releasing hormone agonists, progestins, and danazol are ineffective [3Polyzos NP Fatemi HM Zavos A et al.Aromatase inhibitors in post-menopausal endometriosis.Reprod Biol Endocrinol. 2011; 9: 90Crossref PubMed Scopus (24) Google Scholar]. For postmenopausal women with endometriosis, the first-line treatment should be surgical excision [3Polyzos NP Fatemi HM Zavos A et al.Aromatase inhibitors in post-menopausal endometriosis.Reprod Biol Endocrinol. 2011; 9: 90Crossref PubMed Scopus (24) Google Scholar]. Excision of remaining endometriosis is effective in relieving pain in most patients [4Redwine DB Endometriosis persisting after castration: clinical characteristics and results of surgical management.Obstet Gynecol. 1994; 83: 405-413PubMed Google Scholar, 5Clayton RD Hawe JA Love JC Wilkinson N Garry R Recurrent pain after hysterectomy and bilateral salpingo-oophorectomy for endometriosis: evaluation of laparoscopic excision of residual endometriosis.Br J Obstet Gynaecol. 1999; 106: 740-744Crossref PubMed Scopus (40) Google Scholar]. Postmenopausal endometriosis should be considered in surgically, medically, and naturally menopausal women presenting with chronic pelvic pain and symptoms consistent with endometriosis.

Determining changes in bone metabolism after bariatric surgery in postmenopausal women.

Accelerated bone loss is a known complication after bariatric surgery. Bone mineral density has been shown to decrease significantly after Laparoscopic Roux-en-Y gastric bypass (RYGB). Laparoscopic sleeve gastrectomy (SG) effects on bone density are largely unknown. This should be considered for those with increased preoperative risk for bone loss, such as postmenopausal females. This prospective clinical trial included postmenopausal patients, with BMI ≥ 35k/m2, being evaluated for either RYGB or SG. Patients with history of osteoporosis, estrogen hormone replacement therapy, active smoking, glucocorticoid use, or weight > 295lb were excluded. Patients underwent DEXA scans preoperatively and 1year postoperatively with measurement of total body bone mineral density (BMD) and bone mineral content (BMC) as well as regional site-specific BMD and BMC. A total of 28 patients were enrolled. 16 (57.1%) patients underwent RYGB and 12 (42.9%) patients underwent SG. Median preoperative BMI was 44.2k/m2 (IQR 39.9, 46.6). Median change in BMI at 12months was - 11.3k/m2 (IQR - 12.8, - 7.9). A significant reduction in total body BMC was seen when comparing preoperative measurements to postoperative measurements (2358.32 vs 2280.68 grams; p = 0.002). Regional site BMC and BMD significantly decreased in the ribs and spine postoperatively (p = < 0.02) representing the greatest loss in the axial skeleton. Comparing those who underwent RYGB to SG there was no significant difference between the two groups when evaluating changes in total or regional site BMD. Postmenopausal women were found to have decreased BMD and BMC after RYGB and SG, suggesting that high-risk women may benefit from postoperative DEXA screening. Further study is needed to determine the clinical significance of these findings. It is unknown if these changes in BMD are due to modifiable factors (Vitamin D level, activity level, hormone status, etc.), and whether BMD and BMC is recovered beyond 1year.

SAT-213 Late Diagnosis of Complete Androgen Insensitivity

BACKGROUND: Complete androgen insensitivity (CAIS) is a rare cause of primary amenorrhea and is usually diagnosed in menarche. Patients with CAIS are phenotypically female with a 46, XY karyotype, have elevated testosterone, LH, and FSH levels, and have little or no virilization due to androgen receptor gene mutations. The recommended treatment is orchiectomy due to the increased risk of gonadal malignancy and post-operative hormonal therapy. CLINICAL CASE: A 31-year-old female with no past medical history presented for evaluation of primary amenorrhea. She was born full term with a normal IQ, and no developmental delays or disabilities. The patient had no menstrual periods, minimal breast development, and sparse facial, axillary, and pubic hair growth. She reported having a shallow vaginal canal and absence of a cervix. All of her siblings had normal sexual development with no reproductive or gynecological disorders, and have been able to conceive without any problems. Review of systems was negative for vision changes, galactorrhea, abdominal pain, urinary or defecation problems however positive for headaches. Patient identified as a lesbian. On physical exam the patient had normal vital signs, height of 164 cm and 86 kg (calculated BMI 32); increased muscular tone; no voice deepening; no abdominal pain; sparse hair in the pubic region, upper lip, chin, and bilateral axillae; and Tanner stage 2 breasts. Genitourinary exam was notable for large labia majora, clitoromegaly, palpable testes in inguinal canal, blind vaginal pouch, and absent uterus and cervix. Labs showed normal estradiol (17pg/mL; male 5-52pg/mL), elevated testosterone (273ng/dL; male 249-836ng/dL, female <45ng/dL), LH (24.5 mIU/mL; male 1.7-8.6mIU/mL), and FSH (39.3mIU/ml; male 1.5-12.4mIU/mL), negative urine pregnancy test, normal prolactin, normal thyroid function tests, and a 46, XY karyotype. Imaging demonstrated absent uterus and ovaries, a short blind-ending vagina, and bilateral testes in the inguinal canals. Given elevated FSH, LH and testosterone levels with virilization, the patient was diagnosed with CAIS and underwent bilateral orchiectomy. After surgery, the patient was started on estrogen hormonal replacement therapy. CONCLUSION: Early diagnosis of CAIS is important as this helps guide pharmacotherapies, surgery, malignancy surveillance, genetic counseling, and psychosocial support; all of which help determine a patient’s sexual identity. This case is interesting because the patient was diagnosed far past menarche in her fourth decade, which proved to be psychologically distressing given the patient was unaware of the presence of testes. As androgen insensitivity syndrome presents on a spectrum and any intervention is dependent on phenotype and patient preference, further research is needed to provide evidence-based guidelines regarding therapeutic intervention in any patient with CAIS.

Abstract P1-08-07: Risk factors for high-grade and low-grade DCIS in the cancer prevention study-II nutrition cohort

Abstract Background: Nuclear grade, believed to be established early in carcinogenesis, is an indicator of ductal carcinoma in situ (DCIS) prognosis. Women with high-grade DCIS have a higher risk of local recurrence compared to women with low-grade DCIS. Risk factors for DCIS overall are well-characterized but risk factors by grade are not. Given the prognostic capabilities of grade for DCIS, it is of interest to identify whether risk factors by DCIS grade differ. Methods: Among 75,630 women enrolled in the Cancer Prevention Study-II Nutrition Cohort in 1992-1993, we identified 422 who were diagnosed with low-moderate grade DCIS (i.e. grades 1 or 2) and 355 who were diagnosed with high-grade DCIS (i.e. grade 3) during follow-up through 2013. Beginning in 1997, biennial questionnaires were administered to update exposure status, including screening mammography in the previous two years. For this analysis, these questionnaires were used to partition follow-up time into approximately two-year intervals. Because screening is strongly linked to diagnosis of DCIS, contribution of person-time within a specific interval was conditional on reporting a screening mammogram in the interval prior. Multivariate joint Cox proportional hazards regression models were used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the associations of known breast cancer risk factors with DCIS overall, and with high-grade and low-grade DCIS individually. Results: Parity (HR=0.70; 95% CI: 0.63-0.78, parous vs. nulliparous), smoking status (HR=0.69; 95% CI: 0.58-0.82, current vs. never smoking) and menopausal status (HR=0.79; 95% CI: 0.73-0.87, natural menopause &amp;lt;50 years vs. natural menopause ≥ 50 years) were inversely associated with risk of DCIS overall. Whereas, positive family history of breast cancer (HR=1.46; 95% CI: 1.36-1.57), personal history of benign breast disease (BBD) (HR=1.73; 95% CI: 1.62-1.85), and current use of combination estrogen and progestin hormone replacement therapy (HR=1.15; 95% CI: 1.04-1.28) were associated with higher risk of DCIS. In analyses stratified on DCIS grade, history of BBD was more strongly associated with higher risk of low-grade (HR=2.21; 95% CI: 1.81-2.70) than with high-grade DCIS (HR=1.29; 95% CI:1.04-1.60) (p for heterogeneity=0.001). Current combination estrogen and progestin hormone replacement therapy use was associated with a higher risk of high-grade DCIS (HR=1.40; 95% CI:1.03-1.90) but not low-grade DCIS (HR=1.02; 95% CI: 0.75-1.40), but the difference by grade was not statistically significant (p=0.5). Conclusions: In this study, which is the first to comprehensively assess risk factors by DCIS grade, the association between personal history of BBD and risk of DCIS appeared to differ by grade. Due to limited power for some risk factor analyses, future studies using larger prospective cohorts or pooled data should be conducted to better identify these associations. Citation Format: Puvanesarajah S, Gapstur SM, Gansler T, Patel AV, Gaudet MM. Risk factors for high-grade and low-grade DCIS in the cancer prevention study-II nutrition cohort [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-08-07.

Noi abordări ale osteoporozei în asistenţa medicală primară

Osteoporosis is a disease that affects an increasing number of people, given the tendency of aging populations. Fragile bone and increases risk of bones breaking, their consequences, impairment of quality of life have prompted health policies to provide a greater insight into this condition. It is important to identify the risk factors and start the preventive and curative treatment as early as possible. Current guidelines recommend using the FRAX score to determine the risk of major fracture over the next 10 years, followed by DXA determination. The current guidelines highlight the importance of non-medication measures, calcium and vitamin D intake. Among the therapeutic agents used in the treatment of osteoporosis, the first line are bisphosphonates poor, in case of intolerance, bisphosphonates iv or antibodies anti RANKL (denosumab). Selective estrogen receptor modulators and hormone replacement therapy are not routinely indicated, and recombinant PTH is expensive and is intended for severe and resistant forms. The adherence to treatment is poor, so we need measures to increase prevention, screening and early treatment of osteoporosis, as well as measures to educate the population.

Safety of vaginal oestrogen in hormone replacement therapy

Safety of vaginal oestrogen in hormone replacement therapy