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Background/Objectives: There is evidence of overtreatment in patients with subclinical hypothyroidism (SCH). We aimed to identify the proportion of patients treated for SCH and the determinants of thyroid hormone therapy initiation. Methods: We included a random sample of adult Veterans diagnosed with SCH from 1 January 2016 to 31 December 2018 and conducted univariate and multivariable logistic regression to identify factors associated with levothyroxine initiation. Results: Out of 229 Veterans with SCH [90.0% male, 87.2% White, 99.1% non-Hispanic, median age (interquartile range; IQR) 68 (17) years], 27.5% were treated with levothyroxine. The treated group had a higher proportion of White patients (95.2% vs. 84.2%, p = 0.039), a higher thyrotropin level [median (IQR), 6.98 (2.06) mIU/L vs. 6.14 (1.10) mIU/L, p = 0.0002], a higher proportion of patients with thyrotropin level ≥ 10 mIU/L (11.1% vs. 3.0%, p = 0.021), a lower frequency of confirmatory thyroid testing before initiating levothyroxine (49.2% vs. 97.0%, p < 0.0001), and a similar frequency of thyroid autoimmunity testing (3.2% vs. 0.6%, p = 0.18) compared to the untreated group. In a multivariable logistic regression analysis, White race (OR = 4.50, 95% CI 1.19 to 17.08, p = 0.026) and index thyrotropin level [OR = 1.71, 95% CI 1.24 to 2.35, p = 0.001; for every SD increase (1.6 mIU/L)] were associated with higher odds of treatment. Conclusions: Three in 10 Veterans with SCH received levothyroxine, often based on a single abnormal thyroid test without autoimmunity assessment. White race and higher thyrotropin level were linked to increased odds of starting treatment, indicating potential disparities and the influence of SCH severity on decision-making. [ABSTRACT FROM AUTHOR]

Guidelines for testosterone replacement therapy (TRT) have been well studied and defined in adults, however, this remains less defined for adolescents and young men. There are a variety of conditions in adolescents and young men that necessitate TRT. These conditions range from genetic etiologies such as Kallmann syndrome and Klinefelter syndrome, to acquired causes such as testicular trauma. Conditions can be broadly classified as hypogonadotropic hypogonadism or hypergonadotropic hypogonadism, depending on whether there are concurrently elevated gonadotropins (follicle-stimulating hormone (FSH) and luteinizing hormone (LH)). The decision to initiate TRT in these cases is multifaceted, contributing to the challenge of formulating clear guidelines. In this review, we utilized online sources such as PubMed and Google Scholar to find relevant literature, using key words such as testosterone therapy, adolescents and hormone replacement and hypogonadism in adolescents. This narrative review explores existing literature on TRT in adolescents and young men, encompassing common etiologies of hypogonadism in this population, available TRT therapies, and management and surveillance protocols. Furthermore, it addresses the evolving field of TRT in transgender youth. This study underscores the necessity for additional clinical investigations to explore emerging TRT therapies and establish clear surveillance guidelines tailored to this population.

The results of many studies in recent years indicate a significant impact of pituitary function on bone health. The proper function of the pituitary gland has a significant impact on the growth of the skeleton and the appearance of sexual dimorphism. It is also responsible for achieving peak bone mass, which protects against the development of osteoporosis and fractures later in life. It is also liable for the proper remodeling of the skeleton, which is a physiological mechanism managing the proper mechanical resistance of bones and the possibility of its regeneration after injuries. Pituitary diseases causing hypofunction and deficiency of tropic hormones, and thus deficiency of key hormones of effector organs, have a negative impact on the skeleton, resulting in reduced bone mass and susceptibility to pathological fractures. The early appearance of pituitary dysfunction, i.e. in the pre-pubertal period, is responsible for failure to achieve peak bone mass, and thus the risk of developing osteoporosis in later years. This argues for the need for a thorough assessment of patients with hypopituitarism, not only in terms of metabolic disorders, but also in terms of bone disorders. Early and properly performed treatment may prevent patients from developing the bone complications that are so common in this pathology. The aim of this review is to discuss the physiological, pathophysiological, and clinical insights of bone involvement in pituitary disease. [ABSTRACT FROM AUTHOR]

Objective: The mainstay therapy of hypothyroidism is levothyroxine (LT4). In most cases lifelong treatment is warranted, therefore, choosing adequate doses are of paramount significance. The purpose of this study was to assess several factors that have been proposed to influence LT4 therapy including etiology of hypothyroidism, gender, age, bodyweight, BMI, concomitant drug use, disease severity and time since diagnosis in patients with stable, adequately controlled hypothyroidism. Methods: In this cross-sectional study we analysed past medical history, anthropometric data and biochemical parameters reflecting thyroid function of patients with chronic hypothyroidism who were adequately treated (TSH levels in normal range) with LT4 for at least 6 months. Potential predictors of LT4 requirement were evaluated using uni- and multivariate linear modelling. Results: 191 individuals were enrolled in this study, who were divided into autoimmune (n = 147) and post-surgery (n = 44) groups. Mean age, time since diagnosis and LT4 dose (1.3 versus 1.1 mcg/kgBW) were significantly lower in the autoimmune group. In the post-surgery group age was the only significant (p = 0.016) predictor of LT4 dose. In the autoimmune group BMI (p = 0.001), time since diagnosis (p = 0.023), as well as their interaction (p = 0.012) turned out to be significant predictors of LT4 requirement. Conclusions: Our results implicate the necessity of differentiating between etiologies of hypothyroidism when starting or changing thyroxine replacement therapy. Patient in both groups required significantly lower doses of LT4 replacement, than previous reports suggest, to maintain stable euthyroidism. Distinctly different factors predicted hormone requirement in the two study groups.

Testosterone deficiency encompasses clinically low serum testosterone levels accompanied by signs and symptoms. This testosterone decline is expected in older men and begins in middle age (40 to 64 years) and is commonly treated through Testosterone Replacement Therapy (TRT). This review aims to look at the mechanisms of TRT, physiological and societal motivations to seek TRT, ethical and medical considerations behind its use, and future research directions. From the review of numerous papers looking at testosterone therapy in middle-aged men, various mechanisms for the delivery of testosterone were isolated, each with sufficient risks and benefits. Of all the mechanisms looked at, buccal testosterone and implants had more benefits than others in patient adherence and normal circadian variations in serum testosterone, unlike Intramuscular testosterone. Both physiological and societal changes in middle-aged men cause them to seek therapy. Some of these physiological changes include sarcopenia, reduction in bone mineral density, depressive mood symptoms, reduced libido, and erectile dysfunction. Societal changes, which also influence treatmentseeking, include feelings of "lost masculinity" associated with loss of strength and virility with old age. This societal pressure can lead to a desire to maintain youthful vigor, a significant motivator for seeking TRT. Due to substantial societal and media changes, TRT use in the United States has tripled between 2001 and 2011, raising concerns that many individuals may be receiving treatment without being appropriately informed on the risks and benefits and without clear clinical indications. Although extensive research is available in this field, there remain unanswered questions regarding the effects on non-communicable diseases like cardiovascular disease and cancers. While prostate cancer, in particular, is not related to TRT use, further research is needed to prove the relationship. Additionally, there is untapped potential for TRT beyond the scope of hypogonadism, but researchers have yet to explore these areas of benefit. [ABSTRACT FROM AUTHOR]

Introduction: Turner syndrome (TS) is associated with primary ovarian insufficiency (POI) and most adolescents and young adults (AYA) with TS require treatment with hormone replacement therapy (HRT). International consensus guidelines are unclear on the optimal formulation and dosing for HRT after pubertal induction. This study assessed current HRT practice patterns of endocrinologists and gynecologists in North America. Methods: Email listserv members of the North American Society for Pediatric and Adolescent Gynecology (NASPAG) and the Pediatric Endocrine Society (PES) were invited to complete a 19-question survey to assess HRT treatment preferences for the management of POI after completion of pubertal induction in AYA with TS. Descriptive analysis and multinomial logistic regression to predict factors associated with preferred HRT are presented. Results: 155 providers (79% pediatric endocrinology, 17% pediatric gynecology) completed the survey. Although 87% (135) reported confidence in prescribing HRT, only half (51%, 79) were aware of published guidelines. Factors significantly associated with preferred HRT included specialty (p = 0.032) and number of patients with TS seen every 3 months (p = 0.024). Gynecologists were 4 times less likely than endocrinologists to prefer hormonal contraceptives and 4 times more likely to favor transdermal estradiol dose of 100 μg/day as compared to lower doses. Conclusion: Although most endocrinologists and gynecologists report confidence in prescribing HRT to AYA with TS after pubertal induction, there are clear differences in provider preferences based on specialty and higher volume of patients with TS in their practice. Additional studies on comparative effectiveness of the HRT regimens and evidence-based guidelines are necessary for AYA with TS. [ABSTRACT FROM AUTHOR]

Background: Timing of frozen embryo transfer (FET) within a purported window of implantation is of increasing interest,and there is a paucity of evidence surrounding the transfer of frozen embryos early within these frozen embryo transferprotocols. This study aimed to evaluate whether live birth rates were equivalent after FET of blastocysts 4 days afterluteinizing hormone (LH) surge in a true natural cycle protocol, compared to a hormone replacement (HR) protocol.Materials and Methods: Single-centre, retrospective cohort study involving patients undergoing autologous frozenblastocyst transfer from January 1st, 2013, to December 31st, 2016. Cycles were grouped according to their protocol:true natural cycle (hormonal detection of LH surge with FET scheduled four days later) versus HR cycle (lutealphase gonadotropin-releasing hormone agonist suppression, oral or vaginal estradiol and intramuscular progesteronestarting five days before FET). A total of 850 cycles were included, 501 true natural cycles and 349 HR cycles. Theprimary outcome was the live birth rate, secondary outcomes included clinical pregnancy rate and miscarriage. Logbinomialregression models were performed adjusting for a priori selected variables.Results: Adjusted resulted in live birth rates of 38.7 and 40.4%, [adjusted risk ratio (aRR): 0.96, 95% confidence interval(CI): 0.76-1.22, P=0.729] in the natural cycle and HR groups, respectively. The secondary outcome analyses didnot demonstrate any statistically significant difference in the rate of positive human chorionic gonadotropin (hCG),clinical intrauterine pregnancy rate, or miscarriage rate.Conclusion: The timing of the FET four days after LH surge in a true natural cycle protocol results in equivalent livebirth rates compared to a HR protocol. Results of this study suggest that the window of implantation within the naturalcycle may be less finite than currently believed and further prospective studies evaluating the timing of frozen embryotransfer are warranted.

Background: Timing of frozen embryo transfer (FET) within a purported window of implantation is of increasing interest, and there is a paucity of evidence surrounding the transfer of frozen embryos early within these frozen embryo transfer protocols. This study aimed to evaluate whether live birth rates were equivalent after FET of blastocysts 4 days after luteinizing hormone (LH) surge in a true natural cycle protocol, compared to a hormone replacement (HR) protocol. Materials and Methods: Single-centre, retrospective cohort study involving patients undergoing autologous frozen blastocyst transfer from January 1st, 2013, to December 31st, 2016. Cycles were grouped according to their protocol: true natural cycle (hormonal detection of LH surge with FET scheduled four days later) versus HR cycle (luteal phase gonadotropin-releasing hormone agonist suppression, oral or vaginal estradiol and intramuscular progesterone starting five days before FET). A total of 850 cycles were included, 501 true natural cycles and 349 HR cycles. The primary outcome was the live birth rate, secondary outcomes included clinical pregnancy rate and miscarriage. Logbinomial regression models were performed adjusting for a priori selected variables. Results: Adjusted resulted in live birth rates of 38.7 and 40.4%, [adjusted risk ratio (aRR): 0.96, 95% confidence interval (CI): 0.76-1.22, P=0.729] in the natural cycle and HR groups, respectively. The secondary outcome analyses did not demonstrate any statistically significant difference in the rate of positive human chorionic gonadotropin (hCG), clinical intrauterine pregnancy rate, or miscarriage rate. Conclusion: The timing of the FET four days after LH surge in a true natural cycle protocol results in equivalent live birth rates compared to a HR protocol. Results of this study suggest that the window of implantation within the natural cycle may be less finite than currently believed and further prospective studies evaluating the timing of frozen embryo transfer are warranted. [ABSTRACT FROM AUTHOR]

Fragility fractures, resulting from low‐energy trauma, occur in approximately 1 in 10 Danish women aged 50 years or older. Bilateral oophorectomy (surgical removal of both ovaries) may increase the risk of fragility fractures due to loss of ovarian sex steroids, particularly estrogen. We investigated the association between bilateral oophorectomy and risk of fragility fracture and whether this was conditional on age at time of bilateral oophorectomy, hormone therapy (HT) use, hysterectomy, physical activity level, body mass index (BMI), or smoking. We performed a cohort study of 25,853 female nurses (≥45 years) participating in the Danish Nurse Cohort. Nurses were followed from age 50 years or entry into the cohort, whichever came last, until date of first fragility fracture, death, emigration, or end of follow‐up on December 31, 2018, whichever came first. Cox regression models with age as the underlying time scale were used to estimate the association between time‐varying bilateral oophorectomy (all ages, <51/≥51 years) and incident fragility fracture (any and site‐specific [forearm, hip, spine, and other]). Exposure and outcome were ascertained from nationwide patient registries. During 491,626 person‐years of follow‐up, 6600 nurses (25.5%) with incident fragility fractures were identified, and 1938 (7.5%) nurses had a bilateral oophorectomy. The frequency of fragility fractures was 24.1% in nurses who were <51 years at time of bilateral oophorectomy and 18.1% in nurses who were ≥51 years. No statistically significant associations were observed between bilateral oophorectomy at any age and fragility fractures at any site. Neither HT use, hysterectomy, physical activity level, BMI, nor smoking altered the results. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

3 Hattori, N, Ishihara, T, Matsuoka, N, Saito, T, Shimatsu, A. Anti-thyrotropin autoantibodies in patients with macro-thyrotropin and long-term changes in macro- thyrotropin and serum thyrotropin levels. The specific binding of SP 125 sp I-TSH was displaced almost completely by human TSH and human LH, and human FSH, hCG and hCG partially suppressed it. Keywords: FSH; hCG; hormone replacement; macro-LH; macro-TSH; subclinical hypothyroidism EN FSH hCG hormone replacement macro-LH macro-TSH subclinical hypothyroidism e81 e84 4 04/25/23 20230515 NES 230515 To the Editor, Macro-thyroid stimulating hormone (macro-TSH) is a large molecular weight TSH that mostly comprises a complex of TSH with anti-TSH autoantibodies [[1]], [[2]], [[3]], [[4]], [[5]]. [Extracted from the article]

Hypoparathyroidism (HypoPT) is a disorder characterized by hypocalcemia, low or absent parathyroid hormone (PTH) levels, reduced bone remodeling, and high areal bone mineral density (aBMD). PTH is a therapeutic option, yet data on the prolonged clinical and skeletal effects of PTH treatment are limited. We tracked annual daily doses of calcium and active vitamin D supplements, calciotropic biochemistries, estimated glomerular filtration rate (eGFR), and aBMD measurements in 27 HypoPT patients (16 postsurgical, 11 nonsurgical) who were treated with recombinant human PTH(1‐84) [rhPTH(1‐84)] for at least 8 (n = 27) and up to 12 (n = 14) years. We also performed high‐resolution‐peripheral quantitative computed tomography (HRpQCT) imaging and report results at baseline, 5, 8, and 12 years of rhPTH(1‐84) treatment. With prolonged use of rhPTH, reductions in the need for supplemental calcium and active vitamin D were maintained. The eGFR did not decline. Serum calcium was maintained within the lower limit of the normal range. aBMD by dual‐energy X‐ray absorptiometry (DXA) showed an increase at the lumbar spine and a decrease at the distal 1/3 radius. By HRpQCT, cortical volumetric BMD (vBMD) at the tibia decreased at year 5: −20.0% ± 1.5%. The magnitude of this reduction was mitigated in year 8: −8.5% ± 1.6% and in year 12: −10.3% ± 2.2% but all were significantly below the mean baseline value (p < 0.001). A similar pattern of decline was observed at the radius. Cortical porosity progressively increased at the tibia in year 5: 17.4% ± 10% (p < 0.05), year 8: 55.2% ± 11% (p < 0.001), and year 12: 83.5% ± 14% (p < 0.001). A similar pattern of increase was observed at the radius. Failure load, which was higher than normal at baseline, decreased but remained above normal at year 12. This is the longest experience, to date, with PTH therapy in HypoPT. These results demonstrate sustained biochemical stability but overall decreases in bone mass. © 2023 American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Research question: To investigate the effects of two protocols (hormone replacement therapy (HRT) alone or in combination with tamoxifen) on the endometrium and pregnancy outcome of patients with thin endometrium in frozen-thawed embryo transfer (FET) cycles. Design: A total of 465 infertile patients with thin endometrium who underwent FET between January 2020 to June 2021 at the Drum Tower Hospital affiliated with Nanjing University Medical School were retrospectively analyzed. A total of 187 patients were given tamoxifen in addition to HRT (TMXF-HRT group), whereas 278 patients were given only HRT (HRT group). Clinical data were compared between the two groups, including general characteristics, endometrial thickness, and clinical pregnancy outcomes. Results: There were no significant differences in baseline characteristics of all enrolled patients between two groups. Serum progesterone (P) was higher in HRT group than in the TMXF-HRT group (0.28 ± 0.53 ng/mL vs. 0.15 ± 0.25 ng/mL, P = 0.002). There was a significant increase in endometrial thickness in the TMXF-HRT group compared with the HRT group (OR: 1.54, 95% CI: 1.32-1.75, P < 0.001). There were no significant differences in the clinical pregnancy rate, embryo implantation rate, early miscarriage rate, or live birth rate between these two groups. Conclusion: Although tamoxifen when used in combination with hormone replacement therapy can significantly increase endometrial thickness, it may not have a role in improving the pregnancy outcomes of patients with thin endometrium undergoing FET cycles. [ABSTRACT FROM AUTHOR]

ABSTRACT Fragility fractures, resulting from low‐energy trauma, occur in approximately 1 in 10 Danish women aged 50 years or older. Bilateral oophorectomy (surgical removal of both ovaries) may increase the risk of fragility fractures due to loss of ovarian sex steroids, particularly estrogen. We investigated the association between bilateral oophorectomy and risk of fragility fracture and whether this was conditional on age at time of bilateral oophorectomy, hormone therapy (HT) use, hysterectomy, physical activity level, body mass index (BMI), or smoking. We performed a cohort study of 25,853 female nurses (≥45 years) participating in the Danish Nurse Cohort. Nurses were followed from age 50 years or entry into the cohort, whichever came last, until date of first fragility fracture, death, emigration, or end of follow‐up on December 31, 2018, whichever came first. Cox regression models with age as the underlying time scale were used to estimate the association between time‐varying bilateral oophorectomy (all ages,

Background and Aims: Frozen embryo transfer is a current trend in practice worldwide. Modified Natural Cycle, Hormone Replacement Therapy are common endometrial preparation protocols in Vietnam. The aim of this study was to compare the outcomes of a Modified Natural Cycle vs Hormone Replacement Therapy for Endometrial Preparation for Frozen Embryo Transfer. Method: This was a single center randomized clinical trial. It was conducted in the period between August 2022 and March 2023 in Andrology and Fertility Hospital of Hanoi. A total of 166 patients were randomly allocated to two groups, either the hormone replacement cycle (83 patients) (HRT group) or the modified natural cycle (83 patients) (mNC group). Results: The mean age was 31 vs 30 years in mNC and HRT. The endometrial thickness on the day of Progesterone administration in mNC was higher than HRT (10.99±1.46 và 10.70±1.06 mm), p>0.05. There was no significant difference between mNC group and HRT group regarding implantation rate, clinical pregnancy rate, on-going rate. After adjusting for age, BMI, duration of infertility, type of infertility, history of miscarriage, number of failed embryo transfers, endometrial thickness on the day of Progesterone administration, number of good-quality embryos transferred showed that the clinical pregnancy rate in the HRT was higher than that mNC, but the relationship was not statistically significant with p>0.05. Conclusion: The selection of regimen to use for endometrial preparation for frozen embryo transfer depends on individualized patient treatment, particularly with respect to the selection of the endometrial preparation method particularly with respect to the selection of the endometrial preparation method.

Background: Hormone replacement (HR)-frozen thawed embryo transfer (FET) is preferentially used in Japan. HR-FET needs supplementation of progesterone, but there are few data about the efficacy and safety of vaginal progesterone tablet. The aim of this study is to investigate the efficacy of vaginal progesterone tablet in HR-FET cycle in Japanese patients. Methods: This study was multicenter, single arm, prospective study. Patients with infertility were administered 300 mg/day of vaginal progesterone tablet for luteal phase support in HR-FET cycle from 2015 to 2016. Results: Main outcomes were available for 344 patients, of which 49 in the cleavage stage ET group and 295 in the blastocyst ET group. Ongoing pregnancy rate were 10.2% in cleavage stage ET group and 28.1% in blastocyst ET group. As for the secondary outcomes in the blastocyst ET group, embryo quality of blastocyst, the number of past ET, and maternal age were significantly associated with pregnancy rate at 2 weeks after progesterone administration. Mean serum progesterone level was 12.1 ± 5.3 ng/mL at the day of ET. There was no relationship between the serum progesterone level on ET day and either of pregnancy rates at 2, 4, and 6 weeks after progesterone administration. Conclusions: The efficacy of monotherapy using 300 mg/day of vaginal progesterone tablet in HR-FET was shown and the serum progesterone level on ET day did not affect pregnancy rate. (UMIN000021983)

Conventional therapy for hypoparathyroidism consisting of active vitamin D and calcium aims to alleviate hypocalcemia but fails to restore normal parathyroid hormone (PTH) physiology. PTH replacement therapy is the ideal physiologic treatment for hypoparathyroidism. The double‐blind, placebo‐controlled, 26‐week, phase 3 PaTHway trial assessed the efficacy and safety of PTH replacement therapy for hypoparathyroidism individuals with the investigational drug TransCon PTH (palopegteriparatide). Participants (n = 84) were randomized 3:1 to once‐daily TransCon PTH (initially 18 μg/d) or placebo, both co‐administered with conventional therapy. The study drug and conventional therapy were titrated according to a dosing algorithm guided by serum calcium. The composite primary efficacy endpoint was the proportion of participants at week 26 who achieved normal albumin‐adjusted serum calcium levels (8.3–10.6 mg/dL), independence from conventional therapy (requiring no active vitamin D and ≤600 mg/d of calcium), and no increase in study drug over 4 weeks before week 26. Other outcomes of interest included health‐related quality of life measured by the 36‐Item Short Form Survey (SF‐36), hypoparathyroidism‐related symptoms, functioning, and well‐being measured by the Hypoparathyroidism Patient Experience Scale (HPES), and urinary calcium excretion. At week 26, 79% (48/61) of participants treated with TransCon PTH versus 5% (1/21) wiplacebo met the composite primary efficacy endpoint (p < 0.0001). TransCon PTH treatment demonstrated a significant improvement in all key secondary endpoint HPES domain scores (all p < 0.01) and the SF‐36 Physical Functioning subscale score (p = 0.0347) compared with placebo. Additionally, 93% (57/61) of participants treated with TransCon PTH achieved independence from conventional therapy. TransCon PTH treatment normalized mean 24‐hour urine calcium. Overall, 82% (50/61) treated with TransCon PTH and 100% (21/21) wiplacebo experienced adverse events; most were mild (46%) or moderate (46%). No study drug‐related withdrawals occurred. In conclusion, TransCon PTH maintained normocalcemia while permitting independence from conventional therapy and was well‐tolerated in individuals with hypoparathyroidism. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

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hormone replacement therapy is considered the easiest and most convenient contraceptive method. Commercially available contraceptive combination differs in their composition and concentration of combined constituents. These variations make some of these products preferred over others by consumers based on their side effects profile. The objective of the current research was to ascertain the pro-inflammatory influences of commercially available products. To do so, five groups of rats (ten rats each group) were exposed to Microgynon, Depo-Provera, Marvelon, and Yasmin compared to the control non-treated group. We measured pro-inflammatory markers including d-dimer, TNF-a (tumour necrosis factoralpha), IL(interleukin)-6, IL(interleukin)-1B, and CRP (c-reactive protein). The results confirmed that Yasmin has induced the most deleterious effects on pro-inflammatory markers indicated by significant elevation of IL1B. In conclusion, hormone replacement therapy should be critically indicated and precaution raised inpatient with subclinical diseases, especially cardiovascular ones. [ABSTRACT FROM AUTHOR]

Traditional fertility preservation methods such as embryo or oocyte cryopreservation cannot meet the needs of a cancer patient or for personal reasons. The cryopreservation of ovarian tissue can be an alternative and has become a hot spot to preserve fertility or hormone replacement. The freezing of ovarian tissue can be carried out at any time without ovarian hyperstimulation to retrieve follicles. It is an ideal strategy to preserve reproductive function in children, adolescent cancer patients, and patients who are in urgent need of cancer treatment. With the increasing demands of women with premature ovarian failure or in menopause, ovarian tissue transplantation is also an alternative for hormone replacement that can provide physiological doses of hormone levels, which can avoid a series of risks such as thrombosis, breast cancer, or other hormone-dependent tumors, caused by oral hormone replacement. Hence, ovarian tissue banking can be regarded as a mainstream strategy for fertility preservation and antimenopause hormone replacement in further clinical investigation. [ABSTRACT FROM AUTHOR]

Colorectal cancer remains a major cause of mortality in the USA, despite advances in prevention and screening. Existing therapies focus primarily on generic treatment such as surgical intervention and chemotherapy, depending on disease severity. As personalized medicine and targeted molecular oncology continue to develop as promising treatment avenues, there has emerged a need for effective targets and biomarkers of colorectal cancer. The transmembrane receptor guanylyl cyclase C (GUCY2C) regulates intestinal homeostasis and has emerged as a tumor suppressor. Further, it is universally expressed in advanced metastatic colorectal tumors, as well as other cancer types that arise through intestinal metaplasia. In this context, GUCY2C satisfies many characteristics of a compelling target and biomarker for gastrointestinal malignancies. Colorectal cancer is a leading cause of death in the USA. In recent years, there has been a shift in the field of oncology from generic treatments, such as surgery and chemotherapy, to personalized molecular therapies, which focus on targeting specific attributes of each patient's unique cancer. Guanylyl cyclase C is a receptor expressed in the intestinal tract, where it regulates fluid secretion and prevents tumor formation. Beyond its function in the healthy intestine, it is expressed in colorectal tumors, and other types of cancer, where it regulates transformation. Therefore, guanylyl cyclase C can serve as a useful target in cancer for prevention and therapy, as well as a marker for tumor cell detection. Guanylyl cyclase C is a universal #biomarker and therapeutic target for #colorectalcancer #chemoprevention, treatment and detection [ABSTRACT FROM AUTHOR]

Objective: The mainstay therapy of hypothyroidism is levothyroxine (LT4). In most cases lifelong treatment is warranted, therefore, choosing adequate doses are of paramount significance. The purpose of this study was to assess several factors that have been proposed to influence LT4 therapy including etiology of hypothyroidism, gender, age, bodyweight, BMI, concomitant drug use, disease severity and time since diagnosis in patients with stable, adequately controlled hypothyroidism., Methods: In this cross-sectional study we analysed past medical history, anthropometric data and biochemical parameters reflecting thyroid function of patients with chronic hypothyroidism who were adequately treated (TSH levels in normal range) with LT4 for at least 6 months. Potential predictors of LT4 requirement were evaluated using uni- and multivariate linear modelling., Results: 191 individuals were enrolled in this study, who were divided into autoimmune (n = 147) and post-surgery (n = 44) groups. Mean age, time since diagnosis and LT4 dose (1.3 versus 1.1 mcg/kgBW) were significantly lower in the autoimmune group. In the post-surgery group age was the only significant (p = 0.016) predictor of LT4 dose. In the autoimmune group BMI (p = 0.001), time since diagnosis (p = 0.023), as well as their interaction (p = 0.012) turned out to be significant predictors of LT4 requirement., Conclusions: Our results implicate the necessity of differentiating between etiologies of hypothyroidism when starting or changing thyroxine replacement therapy. Patient in both groups required significantly lower doses of LT4 replacement, than previous reports suggest, to maintain stable euthyroidism. Distinctly different factors predicted hormone requirement in the two study groups., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Three-dimensional printing (3DP) provides the opportunity to personalise different dosage forms and therapeutic regimen where conventional manufacturing processes might not be applicable. Limited work has been done to investigate using 3DP for personalising hormonal intrauterine systems (IUSs). The aim of this work was to prepare 3DP IUS containing progesterone using vat photopolymerisation (VPP)technique. The device was successfully printed and showed a slow release in phosphate buffer (pH 7.4). VPP has the advantages of better printing resolution producing smoother surfaces, and the elimination of the pre-printing process of hot melt extrusion (HME) needed for fused deposition modelling (FDM) method. To the author’s knowledge, this is the first report of using VPP for printing hormone-loaded IUSs.

Hypopituitarism in childhood is a rare, complex disorder that can present with highly variable phenotypes, which may continue into adult life. Pituitary deficits can evolve over time, with unpredictable patterns resulting in significant morbidity and mortality. Hypopituitarism and hypothalamic dysfunction may be associated with challenging comorbidities such as obesity, learning difficulties, behavioral issues, sleep disturbance, and visual impairment. Transition is the purposeful planned movement of adolescents and young adults with chronic conditions from child-centered to adult-oriented health care systems with a shift from parent- to patient-focused care. To achieve effective transition within a health care setting, the inherent challenges involved in the evolution from a dependent child to an independent adult must be recognized. Transition is a critical time medically for patients with hypopituitarism. Complex issues with respect to puberty, attainment of optimal stature, adherence to treatment, and acceptance of the need for life-sustaining medications need to be addressed. For health care professionals, transition is an opportunity for reassessment of the pituitary deficits and the need for lifelong replacement therapies, often against a background of complex psychological issues. We present 4 illustrative cases of hypopituitarism of differing etiologies with diverse clinical presentations. Diagnostic and management processes from clinical presentation to young adulthood are discussed, with a particular focus on needs and outcomes through transition. [ABSTRACT FROM AUTHOR]

Objective: This study was designed to determine the status of dehydroepiandrosterone (DHEA) in women with anorexia nervosa (AN) and to assess the efficacy of DHEA supplementation as a treatment for bone health in women with AN. Method: Studies were retrieved from the PubMed, Embase, Cochrane Library, MEDLINE, and Scopus databases from inception to February 14, 2022. Observational studies that compared serum DHEA levels between women with AN and healthy controls were included for meta‐analysis, and randomized controlled trials (RCTs) that evaluated the effects of DHEA supplementation on bone mass were reviewed. Results: Meta‐analysis of 15 cross‐sectional studies revealed that patients with AN had significantly elevated serum DHEA levels (mean difference (MD) = 311.63 ng/dl; 95% confidence interval (CI), 78.01–545.25) and reduced DHEAS levels (MD = −24.90 μg/dl; 95% CI, −41.72 to −8.07) compared with healthy controls. A systematic review of seven RCTs found that DHEA monotherapy does not improve bone mineral density (BMD) compared with placebo after adjusting for weight gain. While the combination of DHEA and conjugated oral contraceptives has led to increased bone strength and decreased bone loss, the beneficial effect appears to be limited to older adolescents and adults with closed physes. Potential detrimental effects on BMD were identified in younger adolescents with open physes in one study. Discussion: Due to the lack of apparent benefit of DHEA in women with AN and its potential detrimental effect on BMD in young patients with AN, current evidence does not support the use of DHEA. Public Significance: This study demonstrates that women with anorexia nervosa have abnormal levels of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS), which have been suggested by previous studies to play a role in the development of low bone density in this condition. However, current evidence does not support the use of DHEA as a treatment to preserve bone health in patients with anorexia nervosa given the lack of clear benefit following its use and also because of a potential detrimental effect on bone mineral density in young patients with anorexia nervosa. [ABSTRACT FROM AUTHOR]

What is the association between endometrial thickness (EMT) and the birthweight of singleton infants born from frozen-thawed embryo transfer cycles? This retrospective cohort study was conducted from January 2016 to December 2019. Participants were categorized into a natural cycle (NC, n = 8132) group and hormone replacement therapy (HRT, n = 4975) group. Only singleton deliveries were included. The primary outcomes were measures of birthweight and relevant indexes. Multivariable logistic regression and multivariable-adjusted linear regression models that incorporated restricted cubic splines were used. In the HRT group, the risk of delivering a small for gestational age (SGA) infant was increased in women with an EMT <8.0 mm (adjusted odds ratio [aOR] 1.85, 95% confidence interval [CI] 1.17–2.91) compared with women with an EMT of 8.0 to <12.0 mm, and increased with an EMT ≥12.0 mm (aOR 1.85, 95% CI 1.03–3.33). An inverted U-shaped relationship was found between EMT and birthweight in women with HRT. No significant differences were shown in birthweight z -score, or being SGA or large for gestational age, in singletons among the three EMT groups in the natural cycles. A thinner endometrium seen in women undergoing HRT cycles was associated with a lower birthweight z -score, as well as a higher risk of SGA. However, no significant association was observed between EMT and birthweight z -score or SGA in the NC group. It is noteworthy that a thicker endometrium was not associated with a higher birthweight in frozen-thawed embryo transfer (FET) cycles. Women with a thin endometrium who achieve pregnancy require specialized attention, particularly if they are undergoing FET with HRT cycles. [ABSTRACT FROM AUTHOR]

Objective: To study the association of risk-reducing bilateral salpingo-oophorectomy (RRBSO) and breast cancer risk among BRCA pathogenic sequence variants (PSV). Methods: Jewish Israeli BRCA carriers who underwent RRBSO were matched with those who did not--by the mutated gene and year of birth (±1 year). Breast cancer rates were compared. Results: Overall, 127 pairs met the inclusion criteria, 79 (60.6%) pairs harbored BRCA1 PSV and 50 (39.4%) pairs harbored BRCA2 PSV. Median follow up was 8.7 years (interquartile range 4.6-16.1 years). Breast cancer rate for all BRCA carriers combined was not affected by RRBSO (RRBSO 21 [16.5%] versus no RRBSO 31 [24.4%], hazard ratio [HR] for breast cancer 0.61, 95% confidence interval [CI] 0.33-1.14, P = 0.127). No association between RRBSO and breast cancer incidence was noted among BRCA1 PSV carriers. In BRCA2 PSV carriers, RRBSO was associated with a decreased overall breast cancer incidence (HR 0.20, 95% CI 0.44-0.91, P = 0.038), as well as after 5, 10, 15, and 20 years. Hormone replacement therapy was used by 62 PSV carriers, 52 in the RRBSO group and 10 in the no-RRBSO group and did not affect breast cancer risk (P = 0.463). Conclusion: RRBSO is associated with breast cancer risk reduction in Jewish Israeli BRCA2 PSV carriers. Risk-reducing bilateral salpingo-oophorectomy was associated with breast cancer risk reduction in Jewish Israeli BRCA2 pathogenic sequence variant carriers. [ABSTRACT FROM AUTHOR]

The first pump developed by Dr. Kadish and his team in 1963 aimed to "continue subcutaneous insulin infusion". The number of patients using insulin pumps has increased since the 1980s. This historical perspective has labeled pump therapy in endocrinology and metabolism synonymous with insulin pumps. However, certain other hormonal disorders might also benefit from this kind of treatment. Pump therapy is currently the best approach to achieve physiological mimicry. Furthermore, it may help in overcoming pharmacokinetic issues or allergies. Until now, hormone replacement via pumps has been a salvage method for complex cases at the expense of increased costs. However, it is believed that applications of pump treatment will widen in the future owing to the rapidly evolving technology. In this mini review, data on pump use for patients with adrenal insufficiency, hypogonadism, hypoparathyroidism, congenital adrenal hyperplasia, and congenital hyperinsulinism have been briefly summarized. The study has aimed at covering all the relevant clinical studies and important case reports/series. Methods: A systematic literature search has been conducted on PubMed database seeking articles published until May 2021 using a combination of the following Medical Subject Headings terms and keywords: pump "OR" continue infusion "AND" (adrenal insufficiency "OR" Addison "OR" hydrocortisone "OR" hypoparathyroidism "OR teriparatide" "OR" somatostatin "OR" hypogonadism "OR" hypoglycemia "OR" endocrinology "OR" hormone replacement). In addition, the reference publications in the identified articles have also been reviewed. [ABSTRACT FROM AUTHOR]

Key content: Bilateral salpingo‐oophorectomy is indicated for patients with suspected or confirmed gynaecological malignancy.Risk reduction surgery is indicated in patients with a significant family history or a genetic predisposition to developing breast or ovarian cancer.Bilateral salpingectomy with ovarian conservation reduces the risk of ovarian cancer, whilst preserving ovarian function.Oophorectomy prior to the menopause is associated with increased all‐cause mortality and significant menopause related morbidity.Conservative measures such as weight loss, family planning and lifestyle advice could reduce the overall lifetime risk of ovarian cancer. Learning objectives: To understand the rationale of the decision‐making process for bilateral salpingo‐oophorectomy or bilateral salpingectomy with ovarian conversation at the time of hysterectomy for benign disease.To understand the risk–benefit balance of performing oophorectomy in the context of risk reduction of high‐risk patients compared with patients with no genetic predisposition or family history.To consider conservative risk reduction measures that do not involve oophorectomy. Ethical issues: In the absence of family history or genetic predisposition to ovarian or breast cancer, is it ethical to perform routine oophorectomy in perimenopausal or even postmenopausal women?Is it ethical to reduce the risk of ovarian cancer while increasing all‐cause mortality and menopause‐related morbidity?Is it ethical to offer bilateral salpingectomy as a female sterilisation procedure? [ABSTRACT FROM AUTHOR]

The aim of this study was to monitor long‐term changes in bone mineral density (BMD) after menopause and factors affecting BMD. The study population consisted of a random sample of 3222 women from the Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) study, of which 62.1% were postmenopausal at the beginning of the study. This group of women underwent dual‐energy X‐ray absorptiometry (DXA) measurements at the femoral neck every 5 years from baseline (in 1989) up to 25‐year follow‐up. They also responded to risk‐factor questionnaires at 5‐year intervals. During the 25‐year follow‐up, the baseline cohort decreased to 686 women. The women were divided into quartiles based on their baseline BMD. Self‐reported hormone replacement therapy (HRT) and corticosteroid use were divided into ever users and never users. Morbidity was assessed as the total number of self‐reported diseases and BMD‐affecting diseases. The mean 25‐year BMD change was found to be −10.1%, p < 0.001. Higher baseline BMD was associated with higher bone loss rate; the reduction in the highest quartile BMD was 11.1% and in the lowest quartile 7.4% (p = 0.0031). Lower baseline body mass index (BMI) and a greater increase in BMI were found to protect against postmenopausal bone loss (p < 0.001). The lowest bone loss quartile included 15.2% more HRT users than the highest bone loss quartile (p = 0.004). The number of diseases/bone‐affecting diseases, use of vitamin D/calcium supplementation, use of corticosteroids, smoking or alcohol use had no statistical significance for annual bone loss rate. This study presents hitherto the longest (25‐year) BMD follow‐up in postmenopausal women. The linear femoral neck bone loss of 10% was less than previously assumed. A 5‐year BMD change appeared to predict long‐term bone loss in postmenopausal women. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

In addition to hypocalcemia, patients with hypoparathyroidism report poor quality of life (QOL), complaining of fatigue and "brain fog." Parathyroid hormone (PTH) therapy can effectively manage hypocalcemia; however, the effects of PTH treatment on QOL are unclear. Thirty‐one patients with hypoparathyroidism were treated in an open‐label study with full replacement subcutaneous PTH 1‐34 twice daily for up to 5.3 years, with individualized fine‐dosing titration. Prior to initiation of PTH 1‐34, conventional therapy was optimized. The 36‐Item Short Form (SF‐36) Health Survey, Fatigue Symptom Inventory (FSI), and 6‐minute walk test (6MWT) were assessed at PTH start (baseline), every 6 months on PTH, and after PTH discontinuation. The SF‐36 assesses physical function (PF), physical role limitations (RP), bodily pain (BP), general health (GH), vitality (VT), emotional role limitations (RE), social function (SF), and mental health (MH). Compared to population norms, patients at baseline had lower scores in RP, GH, VT, and MH (p < 0.05), consistent with impaired QOL. With PTH therapy, only GH at 6 months and VT at 12 months improved (p < 0.05). At the last treatment time point, RP, VT, and SF improved compared to baseline (p < 0.05). However, follow‐up scores were unchanged from baseline or last PTH treatment, except for SF, which had decreased at follow‐up compared to on‐PTH (p < 0.05). On the FSI, there were no changes in fatigue frequency; perceived interference was improved at 12 and 18 months and composite severity was improved only at 60 months (p < 0.05). The 6MWT measures did not change. In conclusion, hypoparathyroidism is associated with decreased QOL. Despite the bias in open‐label studies to predict improvements in QOL, PTH therapy had limited and non‐sustained effects on QOL, inconclusive changes in fatigue experience, and no change in the 6MWT. Although PTH 1‐34 can adequately manage the hypocalcemia in hypoparathyroidism, its effects on QOL appear to be minimal. © 2021 American Society for Bone and Mineral Research (ASBMR). This article has been contributed to by US Government employees and their work is in the public domain in the USA. [ABSTRACT FROM AUTHOR]

Background The endometrial preparation with stimulating natural cycles for frozen embryo transfer (FET) have benefits like lower cost and ease of use. Objective Comparing the clinical outcome of letrozole versus hormone replacement (HR) for endometrial preparation in women with normal menstrual cycles for FET in artificial reproduction techniques. Materials and Methods A total of 167 participants who had frozen embryos and regular ovulatory cycles were randomly divided into two groups for endometrial preparation. One group (82 women) was stimulated with letrozole 5mg/day and the other group (85 women) was hormonally stimulated by oral estradiol valerate (2 mg three times a day). All participants were followed serially by ultrasonography. Any patient who did not reach optimal endometrial thickness was excluded from the study. Implantation, biochemical and clinical pregnancy and abortion rate were reported. Results There was no significant difference in the mean age, duration, and primary or secondary infertility, cause of the infertility, number, and quality of transferred embryos between the groups. The mean estradiol level on the day of transfer was 643 ± 217 in the HR group and 547 ± 212 in the letrozole group (P = 0.01), which was significantly different. The clinical pregnancy rate was 38.7 in the letrozole group, higher than the HR group (25.3) but not significantly different (P = 0.06). Conclusion For endometrial preparation in women with a normal cycle, letrozole yields higher pregnancy rate although it is not significant; due to its cost, ease in use, and lower side effects, letrozole is a good choice.

Immune checkpoint inhibitors (ICIs) are a relatively newer class of drugs approved for the treatment of malignancies such as melanoma, renal, bladder and lung cancer. Immune-related adverse events (IrAEs) involving the endocrine system are a common side effect of these drugs. The spectrum of endocrine adverse events varies by the drug class. Cytotoxic T-lymphocyte-associated antigen-4 inhibitors commonly cause hypophysitis/hypopituitarism, whereas the incidence of thyroid disease is higher with programmed cell death (PD)-1/ligand (PD-L) protein 1 inhibitors. The focus of this review is to describe the individual endocrinopathies with their possible mechanisms, signs and symptoms, clinical assessment and disease management. Multiple mechanisms of IrAEs have been described in literature including type II/IV hypersensitivity reactions and development of autoantibodies. Patients with preexisting autoimmune endocrine diseases can have disease exacerbation following ICI therapy rather than de novo IrAEs. Most of the endocrinopathies are relatively mild, and timely hormone replacement therapy allows continuation of ICIs. However, involvement of the pituitary-adrenal axis could be lifethreatening if not recognized. Corticosteroids are helpful when the pituitary-adrenal axis is involved. In cases of severe endocrine toxicity (grade 3/4), ICIs should be temporarily discontinued and can be restarted after adequate hormonal therapy. Endocrinologists and general internists need to be vigilant and maintain a high degree of awareness for these adverse events. [ABSTRACT FROM AUTHOR]

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Background: Hypophysitis is described as a rare chronic inflammatory affection of the pituitary gland. However, to date, its pathogenesis has not been completely cleared up. Clinical features are polymorphic, including symptoms related to inflammatory compression and/or hypopituitarism. Laboratory tests determine hormone deficiencies orientating replacement therapy's protocol. MRI of the hypothalamic-pituitary region is crucial in exhibiting major radiological signs such as pituitary homogeneous enlargement and gland stalk's thickening. The etiological diagnosis is still challenging without affecting the management strategy. Corticosteroids have widely been used but a close follow-up without any treatment has also been approved. Case Description: In this report, seven patients with hypophysitis have been collected over a period of 6 years. The average age of our patients was 32.1 years ± 11.8 with a female predominance (71.4%). Panhypopituitarism was objective in 42.9% of cases, a combined deficiency of the hypothalamic-pituitary thyroid, adrenal and gonadal axes in 28.6% of cases. A central diabetes insipidus was noted in 42.9% of the patients. Idiopathic hypophysitis was the most common etiology. The use of long course corticosteroids was required in 28.6% when compressive signs were reported. Conclusion: Hypophysitis remains a rare disease with nonspecific clinical and radiological patterns. Autoimmune origin seems to be the most frequent etiology. No guidelines have been established for hypophysitis management and the evolution is still unpredictable. [ABSTRACT FROM AUTHOR]

Hypertension susceptibility in women increases at the transition to menopause, termed perimenopause, a state characterized by erratic estrogen fluctuation and extended hormone cycles. Elucidating the role of estrogen signaling in the emergence of hypertension during perimenopause has been hindered by animal models that are confounded by abrupt estrogen cessation or effects of aging. In the present study, accelerated ovarian failure (AOF) in estrogen receptor β (ERβ) reporter mice was induced by 4-vinylcyclohexene diepoxide in young mice to model early-stage ovarian failure (peri-AOF) characteristic of peri-menopause. It was found that administering ERb agonists suppressed elevated blood pressure in a model of neurogenic hypertension induced by angiotensin II (AngII) in peri-AOF, but not in age-matched male mice. It was also found that ERb agonist administration in peri-AOF females, but not males, suppressed the heightened NMDAR signaling and reactive oxygen production in ERb neurons in the hypothalamic paraventricular nucleus (PVN), a critical neural regulator of blood pressure. It was further shown that deleting ERb in the PVN of gonadally intact females produced a phenotype marked by a sensitivity to AngII hypertension. These results suggest that ERb signaling in the PVN plays an important role in blood pressure regulation in female mice and contributes to hypertension susceptibility in females at an early stage of ovarian failure comparable to human perimenopause. [ABSTRACT FROM AUTHOR]

Objective: To assess hormonal outcomes and thyroid hormone (TH) replacement after hemithyroidectomy (HT).Study Design: Retrospective chart review.Setting: Quaternary care hospital system.Methods: A retrospective analysis was performed on patients who had an HT at Cleveland Clinic between 2000 and 2010 with outcomes assessed up to 5 years post-HT. Patients with overt hypothyroidism (OH; thyroid-stimulating hormone [TSH] >10 mIU/L, TSH >4.2 mIU/L on thyroid hormone [TH]), subclinical hypothyroidism (SH; TSH >4.2-10 mIU/L, no TH), or euthyroidism (EU; TSH 0.4-4.2 mIU/L, no TH) were compared. Patients with SH who returned to EU were compared to those who continued to have SH. For immediate start on TH, a receiver operating characteristic analysis was performed to determine dosage of TH above which suppression of TSH <0.4 mIU/L was predicted.Results: We identified 335 patients (average age 51 years, 78% female, median follow-up of 50 months). Of the 210 not immediately started on TH, 32.4% were OH, 13.3% were SH, and 54.3% were EU. EU patients were younger (48 years), had more remaining gland, were less likely to have lymphocytic infiltrate, and had a lower preoperative TSH (1.2 mIU/L). In the SH group, 58.3% of patients normalized their TSH. With immediate TH start, 45% developed suppressed TSH. Those on LT4 >1.05 mcg/kg/d were more likely to suppress (sensitivity 89%).Conclusion: Most patients post-HT will remain EU, and immediate start of TH may lead to TSH suppression. Those with SH may ultimately normalize TSH. These findings together suggest that observation may be a better option than TH replacement after HT. [ABSTRACT FROM AUTHOR]