Search Results (391)

Background/Objectives: Osteoporosis remains a leading cause of morbidity in postmenopausal women, yet many high-risk individuals remain undiagnosed or untreated. This study aimed to assess the prevalence of osteoporosis and osteopenia, treatment patterns, and skeletal fragility indicators in a large cohort of postmenopausal women undergoing DXA screening. Methods: We analyzed data from 1669 postmenopausal women aged 40–89 years who underwent DXA evaluation. BMD status was categorized as normal, osteopenia, or osteoporosis. Treatment status was classified based on active antiosteoporotic therapy, calcium/vitamin D supplementation, hormonal therapy (historical use), or no treatment. Logistic regression models were used to explore independent predictors of osteoporosis and treatment uptake. Results: A total of 45.0% of women had osteoporosis and 43.5% had osteopenia. Despite this, 58.5% of the population, over half of women with osteoporosis, were not receiving any active pharmacologic treatment. Bisphosphonates were the most prescribed therapy (17.9%), followed by calcium/vitamin D supplements (20.6%). A prior history of fragility fractures and radiological bone lesions were significantly associated with lower BMD (p < 0.05). Historical hormone replacement therapy (HRT) use was not associated with current BMD (p = 0.699), but women with HRT use reported significantly fewer fractures (p < 0.001). In multivariate analysis, later menopause age and low BMD status predicted higher odds of receiving active treatment. Conclusions: Our findings highlight a substantial care gap in osteoporosis management, with treatment primarily initiated reactively in more severe cases. Improved screening and earlier intervention strategies are urgently needed to prevent fractures and reduce the long-term burden of osteoporosis. Full article

Background/Objectives: Pituitary tumors account for over 90% of all sellar region masses. However, a spectrum of rare neoplastic, inflammatory, infectious, and vascular lesions—benign and malignant—can arise in the intra- and parasellar compartments and clinically and radiologically mimic PitNETs. We report a cohort of 47 such rare and cystic midline intracranial lesions, emphasizing their distinctive morphological, clinical, and imaging features and the personalized treatment strategies applied. Methods: In this retrospective single-center study, we reviewed all patients treated for suspected PitNETs via transsphenoidal approach between 2015 and 2024. Of 529 surgical cases, we excluded confirmed PitNETs, meningiomas, and classical intradural craniopharyngiomas. Collected data encompassed patient demographics, tumor characteristics, presenting symptoms, extent of resection or medical therapy, endocrine outcomes, and follow-up information. Results: Among all 529 patients who underwent surgical treatment for sellar lesions from 2015 to 2024, 47 cases (8.9%) were identified as rare or cystic masses. Forty-six underwent transsphenoidal resection; one patient with hypophysitis received corticosteroid therapy alone. Presenting symptoms included headache (n = 16), dizziness (n = 5), oculomotor disturbances (n = 2), and visual impairment (n = 17). Endocrine dysfunction was found in 30 patients, 27 of whom required hydrocortisone replacement. Histopathological diagnoses were led by colloid cysts (n = 14) and Rathke’s cleft cysts (n = 11). The remaining 22 cases comprised plasmacytoma, germinoma, lymphoma, pituicytoma, inverted papilloma, metastatic carcinoma, chordoma, nasopharyngeal carcinoma, chloroma, and other rare entities. Preoperative imaging diagnosis proved incorrect in 38% (18/47) of cases, with several lesions initially misidentified as PitNETs. Conclusions: Nearly 9% of presumed PitNETs were rare, often benign or inflammatory lesions requiring distinct management. Most could be safely resected and demonstrated excellent long-term outcomes. Yet, despite advanced imaging techniques, accurate preoperative differentiation remains challenging, with over one-third misdiagnosed. Clinical red flags—such as early hormone deficits, rapid progression or atypical imaging findings—should prompt early interdisciplinary evaluation and, when indicated, image-guided biopsy to avoid unnecessary surgery and ensure tailored therapy. Full article

Thyroid hormones (thyroxine, T₄, and triiodothyronine, T₃) are indispensable for sustaining vertebrate life, and their deficiency gives rise to a wide range of symptoms characteristic of hypothyroidism, affecting 5–10% of the world’s population. The precursor for thyroid hormone synthesis is thyroglobulin (Tg), a large iodoglycoprotein consisting of upstream regions I-II-III (responsible for synthesis of most T₄) and the C-terminal CholinEsterase-Like (ChEL) domain (responsible for synthesis of most T₃, which can also be generated extrathyroidally by T₄ deiodination). Using CRISPR/Cas9-mediated mutagenesis, we engineered a knock-in of secretory ChEL into the endogenous TG locus. Secretory ChEL acquires Golgi-type glycans and is properly delivered to the thyroid follicle lumen, where T₃ is first formed. Homozygous knock-in mice are capable of thyroidal T₃ synthesis but largely incompetent for T₄ synthesis such that T₄-to-T₃ conversion contributes little. Instead, T₃ production is regulated thyroidally by thyrotropin (TSH). Compared to cog/cog mice with conventional hypothyroidism (low serum T₄ and T₃), the body size of ChEL-knock-in mice is larger; although, these animals with profound T₄ deficiency did exhibit a marked elevation of serum TSH and a large goiter, despite normal circulating T₃ levels. ChEL knock-in mice exhibited a normal expression of hepatic markers of thyroid hormone action but impaired locomotor activities and increased anxiety-like behavior, highlighting tissue-specific differences in T₃ versus T₄ action, reflecting key considerations in patients receiving thyroid hormone replacement therapy. Full article

Menopause is characterized by a decline in estrogen levels, leading to symptoms such as vasomotor instability, osteoporosis, and increased cardiovascular and cognitive risk. Hormone replacement therapy (HRT) remains the gold standard for managing menopausal symptoms; however, concerns regarding its long-term safety, including elevated risks of cancer and cardiovascular events, have prompted interest in alternative therapies. Phytoestrogens, particularly the isoflavones daidzein and genistein, are plant-derived compounds structurally similar to 17β-estradiol (E2) and capable of binding estrogen receptors. Found abundantly in soybeans and red clover, these compounds exhibit selective estrogen receptor modulator (SERM)-like activity, favoring ERβ over ERα, which underlies their tissue-specific effects. In vitro, in silico, and in vivo studies demonstrate their ability to modulate estrogenic pathways, inhibit oxidative stress, and influence reproductive and neurological function. Clinical trials show that daidzein and genistein, especially in equol-producing individuals, can reduce vasomotor symptoms such as hot flashes and night sweats. While results across studies vary, consistent findings support their safety and modest efficacy, particularly for women unable or unwilling to use HRT. Pharmacokinetic studies reveal moderate bioavailability and interindividual variability due to gut microbiota metabolism. At dietary levels, these compounds are generally safe, although high-dose supplementation is discouraged in individuals with hormone-sensitive cancers. Emerging evidence suggests lifelong consumption of soy-based foods may reduce cancer risk. In conclusion, daidzein and genistein represent promising, well-tolerated natural alternatives to conventional HRT, offering symptom relief and additional health benefits. Further research is warranted to optimize dosing, improve clinical outcomes, and clarify long-term safety in diverse populations, particularly with genetic variations in isoflavone metabolism. Full article

Osteoporosis and sarcopenia are two aspects of the geriatric syndrome that frequently occur together and affect one another in a condition referred to as osteosarcopenia. Preventive and treatment options for osteosarcopenia exist but are mainly focused on the treatment of osteoporosis, as there is still no FDA-approved treatment for sarcopenia. Drugs for osteoporosis include antiresorptive and anabolic drugs and hormonal replacement therapies and are prescribed based on age, BMD and other patient characteristics, which, however, do not include the possible co-existence of sarcopenia. As several studies and clinical trials have shown that the pharmacological treatment of osteoporosis can also affect muscle tissue, in either a positive or negative manner, sarcopenia should be another factor affecting the choice of treatment, especially when facing equal treatment options for osteoporosis. The aim of this review was to summarize our current knowledge on the effects of FDA-approved drugs for the treatment of osteoporosis on muscle quality, mass and function. A better understanding of the effects that certain drugs have on muscle tissue might in the future help us to simultaneously at least partially also address the wasting of muscle tissue and avoid further pharmacologically induced decline. Full article

Background/Objectives: Bisphosphonates may influence vascular calcification and atheroma formation via farnesyl pyrophosphate synthase inhibition in the mevalonate pathway regulating bone and lipid metabolism. However, the clinical impact of NCB use on cardiovascular outcomes remains uncertain, largely due to methodological heterogeneity in prior studies. We aimed to evaluate the association between nitrogen-containing bisphosphonate (NCB) therapy and coronary artery calcium (CAC) progression, as well as the incidence of cardiovascular disease (CVD) and coronary heart disease (CHD) events. Methods: From 6814 participants in MESA Exam 1, we excluded males (insufficient male NCB users in the MESA cohort), pre-menopausal women, baseline NCB users, and users of hormone replacement therapy, raloxifene, or calcitonin. Among 166 NCB initiators and 1571 non-users with available CAC measurements, propensity score matching was performed using the available components of FRAX, namely age, race, BMI, LDL cholesterol, alcohol, smoking, and steroid use, and baseline CAC yielded 165 NCB initiators matched to 473 non-users (1:3 ratio). Linear mixed-effects models evaluated CAC progression, and Cox models analyzed incident CVD and CHD events. Results: In the overall cohort, NCB use was not significantly associated with CAC progression (annual change: −0.01 log Agatston units; 95% CI: −0.05 to 0.01). However, among participants with a baseline estimated glomerular filtration rate (eGFR) < 65 mL/min/1.73 m², NCB use was associated with attenuated CAC progression compared with non-users (−0.06 log Agatston units/year; 95% CI: −0.12 to −0.007). No significant association was observed between NCB use and incident CVD events in the overall cohort (HR: 0.90; 95% CI: 0.60−1.36) or within kidney function subgroups. Conclusions: Incident NCB use among postmenopausal women with mild or no CAC at baseline was associated with reduced CAC progression only in women with impaired kidney function. However, this association did not correspond to a decreased risk of subsequent cardiovascular events, suggesting that the observed imaging benefit may not translate into meaningful clinical association. Full article

Background: Hashimoto’s thyroiditis (HT), the most prevalent autoimmune thyroid disorder in reproductive-age women, has been linked to diminished ovarian reserve and subfertility. This study aimed to evaluate the relationship between HT and key fertility parameters, including hormonal markers and reproductive outcomes, while also exploring the potential impact of thyroid hormone replacement therapy. Methods: A retrospective observational study was conducted on 86 women undergoing fertility evaluation. Participants were divided into two groups based on anti-thyroid peroxidase antibodies (ATPO): the HT group (n = 49) and the control group (n = 37). Among women with HT, 57% were receiving levothyroxine (Euthyrox^®) at the time of assessment. Variables analyzed included serum levels of anti-Müllerian hormone (AMH), thyroid-stimulating hormone (TSH), insulin resistance index (HOMA-IR), number of oocytes retrieved, blastocysts formed, pregnancies achieved, and live births. Statistical methods included t-tests, Mann–Whitney U tests, Pearson/Spearman correlations, and linear regression models. Results: Women in the HT group had slightly lower AMH levels and oocyte counts compared to controls, though these differences did not reach statistical significance. TSH values were higher in the HT group and showed a significant negative correlation with blastocyst formation (p = 0.03). Although TSH also showed negative trends with oocyte count, pregnancies, and live births, these correlations did not reach statistical significance. A post-hoc subgroup analysis revealed that HT patients receiving levothyroxine tended to have higher numbers of oocytes retrieved and blastocysts formed compared to untreated HT patients, suggesting a possible beneficial effect of thyroid hormone replacement, although the differences were not statistically significant. Conclusions: HT is associated with subtle but clinically relevant impairments in ovarian reserve and reproductive potential. Thyroid hormone replacement may offer modest benefits and should be considered in the individualized management of fertility in women with thyroid autoimmunity. Full article

Background and Objectives: This study investigated changes in quality of life (QOL), depression, and menopausal symptoms after surgical menopause, and the efficacy of hormone replacement therapy (HRT) in gynecological cancer survivors (GCS). Materials and Methods: Participants undergoing gynecologic cancer surgery (N = 155) were divided into those who received HRT after surgical menopause (SH, N = 47), those after surgical menopause (SM, N = 54), and those after natural menopause (NM, N = 54). QOL, depression, and menopausal symptoms were assessed using the Functional Assessment of Cancer Therapy-General (FACT-G), Center for Epidemiologic Studies Depression Scale (CES-D), and Endocrine Symptoms Subscale-19 (ESS-19), respectively. Assessments were conducted before and at 6 and 12 months after surgery. Results: In SH and SM, FACT-G and CES-D were worst before surgery, gradually improved by 6 months, and remained stable for the following 6 months. FACT-G and CES-D showed an inverse relationship. ESS-19 did not change in SH and SM for 12 months. Among the items on the ESS-19, worsened vasomotor symptoms (VMSs), assessed with ES1, showed more improvement in SH than in SM, while worsened arthralgia assessed with BRM1 was maintained in SM. Multivariate analysis showed that HRT was not independently correlated with changes in QOL and depression status. Conclusions: In GCS, the prevalence of depression was highest at cancer disclosure along with declining QOL. QOL gradually improved by 6 months after surgery in SH and SM, but not in NM. Although menopausal HRT is known to alleviate VMS, anxiety, and depression, its efficacy for cancer-related emotional distress and the associated decline in QOL seems limited. Full article

Background/Objectives: Hypothyroidism and thyroid autoimmunity have a negative effect on women’s sexual health, which is only partially reversed by thyroid hormone substitution. Sexual functioning in thyroid disorders after delivery has been poorly researched. The aim of our study was to compare the effect of levothyroxine on sexual response and depressive symptoms in women with postpartum thyroiditis (PPT) and different vitamin D status. Methods: The study population consisted of three matched groups of women with the hypothyroid phase of PPT: two groups with subclinical and one with overt thyroid hypofunction. Each group included similar numbers of women with normal and low vitamin D status. For the following six months, one group of women with subclinical hypothyroidism and all women with overt thyroid hypofunction received levothyroxine. At the beginning and at the end of the study, all participants completed questionnaires evaluating female sexual function (FSFI) and depressive symptoms (BMI-II). The remaining outcomes of interest included thyroid antibody titers, and the serum levels of 25-hydroxyvitamin D, TSH, free thyroid hormones, sex hormones, and prolactin. Results: Before levothyroxine substitution, women with overt and subclinical disease differed in the total FSFI score, all domain scores, and the overall BDI-II score. Within each study group, domain scores for desire were greater in women with vitamin D sufficiency than in those with vitamin D deficiency/insufficiency. Testosterone and estradiol levels were lower in women with overt than in women with subclinical hypothyroidism, while the opposite relationship was found for prolactin. Levothyroxine treatment improved all domains of female sexual function and reduced the total BDI-II score in both patients with overt and subclinical hypothyroidism and normal vitamin D status. In women with vitamin D deficiency/insufficiency, the impact of this agent was limited to arousal, lubrication, and sexual satisfaction. Levothyroxine replacement reduced thyroid antibody titers only in women with normal vitamin D status. The impact on testosterone was limited to women with normal vitamin D status, and was more pronounced in women with overt than subclinical disease. The effect on estradiol and prolactin, observed only in overt disease, was unrelated to vitamin D status. The increase in sexual functioning correlated with the following: 25-hydroxyvitamin D levels (in vitamin D-deficient/insufficient women); the impact on thyroid peroxidase antibodies, free triiodothyronine and testosterone (for desire and arousal); and the changes in the overall BDI-II score. Five years later, the quality of life was better in vitamin D-sufficient women receiving levothyroxine in the postpartum period. Conclusions: Low vitamin D status attenuates the impact of levothyroxine on female sexual function and depressive symptoms in women with the hypothyroid phase of PPT. Full article

Background/Objectives: Frontal fibrosing alopecia (FFA) is a scarring alopecia with an unclear aetiology, primarily affecting postmenopausal women. This study aims to identify potential risk factors contributing to FFA development and progression, as well as provide a clinical profile to aid in the differential diagnosis. Methods: The study included 19 women diagnosed with FFA. The participants completed a 20-question survey based on a literature review of potential risk factors. Statistical analyses were performed to investigate the associations between patient characteristics and FFA. Results: All patients were female and their mean age was 60.58 years (SD = 12.81). In 63.1% of the cases, FFA onset occurred postmenopause, with a mean latency of 8.17 years. In the majority of cases, the diagnostic delay exceeded five years. The average menarche age was 13.68 years (SD = 2.06), whereas late menarche (≥15 years) was found in two subjects. A history of reproductive organ or breast malignancy was reported by 42.1% of the patients, which frequently required surgery. Most subjects did not receive hormone replacement therapy, or hormonal contraception. The most prevalent comorbidity was hypothyroidism (89.47%). Although smoking was rare among the subjects, hair colouring was quite common, yet no participant underwent scalp aesthetic procedures. In 47.4% of cases, scalp itching or pain was present. Sunscreens were frequently used, mostly on a daily or seasonal basis. Conclusions: FFA predominantly affects women in their early 60s, often following the menopause. In our study, a tendency toward an early menopause and an above-average menarche age of the subjects was observed. In the analysed group, only reproductive and breast cancers were reported, which requires further investigation. Frequent β-blocker use, second only to levothyroxine, may suggest that they play a role in FFA pathogenesis. Itching and pain of the scalp may contribute to the correct diagnosis, although these symptoms are not universal. Moreover, sunscreens were indicated as a potential trigger, yet avoiding them should not be routinely recommended due to the risk of carcinogenesis. The variability in the diagnostic delay emphasises the need for increasing clinician awareness and conducting further research. Full article

The goal of gender-affirming hormone therapy (GAHT) is to align an individual’s physical characteristics with their gender identity by suppressing endogenous sex hormones and replacing them with those consistent with their gender. Transgender women undergoing GAHT are at higher risk of cardiovascular complications, and since clinical evidence suggests that hypertension is associated with increased bone loss, we investigated the effects of estrogen treatment on bone health in a hypertensive transgender animal model. Male spontaneously hypertensive rats were orchiectomized (Orch), and half of them received estrogen treatment (Orch + Es), while a third group remained intact as controls. Bone marrow progenitor cells (BMPCs) were isolated to assess osteogenic potential, and femurs were collected for histological and mechanical analysis. BMPCs from Orch + Es rats exhibited enhanced osteogenic potential compared to those from Orch rats. Histological analysis revealed a higher number of osteocytes and fewer adipocytes in the Orch + Es group. Mechanical testing showed reduced bone strength in Orch rats, which was partially preserved in Orch + Es animals. In conclusion, estrogen administration mitigated the deleterious effects of testosterone depletion on BMPCs and provided protective effects on bone structure and strength in this preclinical model of GAHT in hypertensive rats. Full article

Background: One of the most debated topics in experimental and clinical endocrinology is the impact of hypo- and hyper-somatotropism on the extension/shortening of the lifespan, the results of experimental, clinical, and epidemiological studies being extremely conflicting. Biological age, a surrogate of lifespan, can be measured through different methods, including the age-related epigenetic modifications of DNA. Objective: The present study aimed to evaluate the biological (epigenetic) age and age acceleration in a group of growth hormone (GH)-deficient (GHD) children (F/M = 5/5; age: 11.0 ± 2.7 years), treated with recombinant human GH (rhGH) for 6 months at a daily dose of 0.025–0.035 mg/kg. Results: Treatment with rhGH significantly increased height velocity and circulating insulin-like growth factor 1 (IGF-1) levels. Biological and chronological ages were significantly correlated at baseline and after 6 months of rhGH replacement therapy. Treatment with rhGH reduced age acceleration, an effect that became significant only after adjustment for IGF-1. In a linear regression model for longitudinal data, after adjustment for rhGH treatment, age acceleration was significantly associated with IGF-1 levels, an effect missing when considering the interaction rhGH treatment × age acceleration at 6 months of rhGH treatment. Conclusions: (rh)GH, when administered to GHD children, exerts anti-ageing effects, which become evident after removal of the presumably pro-ageing effects of IGF-1. Full article

Sex-related differences are found not only in the reproductive system but also across various biological systems, such as the cardiovascular system. Compared with premenopausal women, cardiovascular disease (CVD) tends to occur more frequently in adult men and postmenopausal women (Post-MW). Also, during the reproductive years, sex hormones synthesized and released into the blood stream affect vascular function in a sex-dependent fashion. Estrogen (E2) interacts with estrogen receptors (ERs) in endothelial cells, vascular smooth muscle, and the extracellular matrix, causing both genomic and non-genomic effects, including vasodilation, decreased blood pressure, and cardiovascular protection. These observations have suggested beneficial effects of female sex hormones on cardiovascular function. In addition, the clear advantages of E2 supplementation in alleviating vasomotor symptoms during menopause have led to clinical investigations of the effects of menopausal hormone therapy (MHT) in CVD. However, the findings from these clinical trials have been variable and often contradictory. The lack of benefits of MHT in CVD has been related to the MHT preparation (type, dose, and route), vascular ERs (number, variants, distribution, and sensitivity), menopausal stage (MHT timing, initiation, and duration), hormonal environment (progesterone, testosterone (T), gonadotropins, and sex hormone binding globulin), and preexisting cardiovascular health and other disorders. The vascular effects of sex hormones have also prompted further examination of the use of anabolic drugs among athletes and the long-term effects of E2 and T supplements on cardiovascular health in cis- and transgender individuals seeking gender-affirming therapy. Further analysis of the effects of sex hormones and their receptors on vascular function should enhance our understanding of the sex differences and menopause-related changes in vascular signaling and provide better guidance for the management of CVD in a gender-specific fashion and in Post-MW. Full article

Menopause is associated with significant hormonal and reproductive changes in women. Evidence documents interindividual differences in the signs and symptoms associated with menopause, including cognitive decline. Hypothesized reasons for the cognitive decline include changes in hormone levels, especially estrogen, but study findings have been inconsistent. Hormone replacement therapies (HRTs) are often recommended to alleviate menopause-related symptoms in both peri- and postmenopausal women. However, the North American Menopause Society does not recommend the use of HRT for the management of cognitive complaints in perimenopausal women due to lack of evidence. Additionally, there are many women for which the use of HRT is contraindicated. As such, it would be helpful to have an alternative method for alleviating symptoms, including declines in cognition, during the menopause transition. Iron supplementation may be a promising candidate as it has been associated with improved cognitive performance in premenopausal women with iron deficiency and iron deficiency anemia. Because many women will experience heavy blood losses during perimenopause, they are at risk of becoming iron deficient and/or anemic. The use of iron supplementation in women with iron deficiency may serve to not only improve iron status but also to alleviate many of the signs and symptoms associated with perimenopause (lethargy, depressed affect, etc.), including cognitive decline. However, evidence to inform treatment protocols is lacking. Well-designed studies of iron supplementation in perimenopausal women are needed in order to understand the potential of such supplementation to alleviate the cognitive decline associated with perimenopause. Full article

Background and objective: Menopause is a significant physiological milestone in a woman’s life, coinciding with increased cardiovascular disease (CVD) risk due to various health-related changes. This narrative review focuses on cardiovascular health-related alterations during menopause and their implications on vascular function. Methods: An electronic database search was performed, drawing from sources such as PubMed and Google Scholar. Publications were included if they addressed CVD risk in peri- and postmenopausal women, and examined the impact of hormonal changes, traditional risk factors (e.g., hypertension, hyperlipidemia, diabetes), or lifestyle factors (e.g., diet, physical activity) on CVD. Results: Estrogen deficiency is pivotal, leading to adverse effects such as endothelial dysfunction, increased arterial stiffness, and lipid profile deterioration. Characteristics of menopause, including the age at onset, type or stage of menopause, and severity of symptoms, further modulate CVD risk. Additionally, the impact of traditional risk factors is amplified during this period. Strategies for the prevention of CVD in menopausal women are critically assessed, with a focus on lifestyle modifications, dietary interventions, and physical activity. Conclusions: This narrative review describes the potential benefits and risks of hormone therapy, alongside lipid-lowering therapies. Emphasis is placed on individualized risk assessment and management, highlighting the need for regular cardiovascular screenings and proactive management of risk factors. Full article