Systematic review and meta-analysis of the effects of menopause hormone therapy on cognition.

Introduction: Despite evidence from preclinical studies suggesting estrogen's neuroprotective effects, the use of menopausal hormone therapy (MHT) to support cognitive function remains controversial. Methods: We used random-effect meta-analysis and multi-level meta-regression to derive pooled standardized mean difference (SMD) and 95% confidence intervals (C.I.) from 34 randomized controlled trials, including 14,914 treated and 12,679 placebo participants. Results: Associations between MHT and cognitive function in some domains and tests of interest varied by formulation and treatment timing. While MHT had no overall effects on cognitive domain scores, treatment for surgical menopause, mostly estrogen-only therapy, improved global cognition (SMD=1.575, 95% CI 0.228, 2.921; P=0.043) compared to placebo. When initiated specifically in midlife or close to menopause onset, estrogen therapy was associated with improved verbal memory (SMD=0.394, 95% CI 0.014, 0.774; P=0.046), while late-life initiation had no effects. Overall, estrogen-progestogen therapy for spontaneous menopause was associated with a decline in Mini Mental State Exam (MMSE) scores as compared to placebo, with most studies administering treatment in a late-life population (SMD=-1.853, 95% CI -2.974, -0.733; P = 0.030). In analysis of timing of initiation, estrogen-progestogen therapy had no significant effects in midlife but was associated with improved verbal memory in late-life (P = 0.049). Duration of treatment >1 year was associated with worsening in visual memory as compared to shorter duration. Analysis of individual cognitive tests yielded more variable results of positive and negative effects associated with MHT. Discussion: These findings suggest time-dependent effects of MHT on certain aspects of cognition, with variations based on formulation and timing of initiation, underscoring the need for further research with larger samples and more homogeneous study designs.

The combination of dydrogesterone and micronized vaginal progesterone can render serum progesterone level measurements on the day of embryo transfer and rescue attempts unnecessary in an HRT FET cycle.

PURPOSE: To evaluate the role of serum progesterone (P4) on the day of embryo transfer (ET) when dydrogesterone (DYD) and micronized vaginal progesterone (MVP) are combined as luteal phase support (LPS) in a hormone replacement therapy (HRT) frozen ET (FET) cycles. METHODS: Retrospective study, including single euploid HRT FET cycles with DYD and MVP as LPS and P4 measurement on ET day. Initially, patients with P4 levels < 10 ng/ml increased MVP to 400 mg/day; this "rescue" was abandoned later. RESULTS: 560 cycles of 507 couples were included. In 275 women, serum P4 level was < 10 ng/ml on the ET day. Among those with low P4 levels, MVP dose remained unchanged in 65 women (11.6%) and was increased in 210 women (37.5%). Women with P4 levels ≥ 10 ng/ml continued LPS without modification. Overall pregnancy rates in these groups were 61.5% (40/65), 54.8% (115/210), and 48.4% (138/285), respectively (p = n.s.). Association of serum P4 levels with ongoing pregnancy rates was analyzed in women without any additional MVP regardless of serum P4 levels (n = 350); multivariable analysis (adjusted for age, BMI, embryo quality (EQ)) did not show a significant association of serum P4 levels with OPR (OR 0.96, 95% CI 0.90-1.02; p = 0.185). Using inverse probability treatment weights, regression analysis in the weighted sample showed no significant association between P4 treatment groups and OP. Compared to fair EQ, the transfer of good EQ increased (OR 1.61, 95% CI 1.22-2.15; p = 0.001) and the transfer of a poor EQ decreased the odds of OP (OR 0.73, 95% CI 0.55-0.97; p = 0.029). CONCLUSION: In HRT FET cycle, using LPS with 300 mg/day MVP and 30 mg/day DYD, it appears that serum P4 measurement and increase of MVP in patients with P4 < 10 ng/ml are not necessary.

Testosterone Replacement Therapy in Orthopaedic Surgery.

Testosterone replacement therapy (TRT) is an indicated treatment of several medical conditions including late-onset hypogonadism, congenital syndromes, and gender affirmation hormonal therapy. Increasing population age, medical benefits, and public awareness of TRT have resulted in increased prevalence of its utilization. However, TRT is not without concern for adverse risks including venous thromboembolic complications, cardiovascular events, and prostate issues. In the field of orthopaedic surgery, research is beginning to delineate the complex relationship between TRT and the development of orthopaedic conditions and potential effects on surgical interventions and outcomes. In this review, we discuss current literature surrounding TRT and subsequent development of osteoarthritis, incidence of total joint arthroplasty, musculotendinous pathology, postoperative infection risk, improvements in postoperative rehabilitation metrics, enhancement of osseous healing, and increased bone-implant integration. The authors suggest future areas of investigation that may provide guidance on how surgeons can mitigate adverse risks while optimizing benefits of TRT in the orthopaedic patient.

Assessment of knowledge, understanding and awareness of Chinese women clinical staff towards menopause hormone therapy: a survey study.

Menopausal Hormone Therapy (MHT) is recommended for climacteric peri- and postmenopausal symptoms. The rate of use of MHT in China is much lower than the western regions. Therefore, a survey was conducted for the understanding and utilization of MHT among clinical staff in various hospitals of China. A total of 3216 eligible questionnaires were included for the evaluation. According to 19.2% participant opinion, MHT could relieve menopausal symptoms, whereas the majority had no knowledge of the benefits and risks of MHT. The most common concern about MHT was the risk of cancer and about 430 (13.4%) and 176 (5.5%) participants were apprehensive that MHT could increase the risk of breast and endometrial cancer, respectively. This survey demonstrated that the knowledge of clinical staff was not comprehensive and they should be educated more about the use of MHT so that this knowledge can be imbibed into the general population.Impact StatementWhat is already known on this subject? Menopausal Hormone Therapy (MHT) is recommended for climacteric peri- and postmenopausal symptoms. The rate of use of MHT in China is much lower than the western regions.What do the results of this study add? Only 19.2% of the respondents were of the opinion that MHT could relieve menopausal symptoms. The most common concern about MHT was the risk of cancer and about 430 (13.4%) and 176 (5.5%) participants were apprehensive that MHT could increase the risk of breast and endometrial cancer.What are the implications of these findings for clinical practice and/or further research? The survey demonstrated that Chinese medical professionals had some understanding about MHT, but their knowledge was not comprehensive. Thus, it is necessary to educate these medical professionals which in turn will help them to imbibe this knowledge among the general population.

A rare case of a 34-year-old patient diagnosed late with Kallmann syndrome: case report.

Kallmann syndrome (KS) is a rare genetic disorder manifested by the combination of hypogonadotropic-hypogonadism and olfactory dysfunction. It is usually diagnosed at 14 - 16 years of age due to delayed puberty. However, delays in diagnosis have been reported in a few cases. We presented a 34-year-old man presented with primary infertility as the chief complaint. Physical examination revealed bilateral gynecomastia, Tanner stage 2, and anosmia. Hormonal studies show a hypogonadotropic hypogonadism profile. Genetic testing revealed a normal male karyotype. Abdominal ultrasonography (USG) revealed a small prostate, and testicular USG demonstrated small testicles. Neuroimaging study revealed olfactory bulb agenesis and hypoplasia of the olfactory sulcus. Treatment was done by testosterone replacement therapy, and the patient is now on a regular follow-up. In conclusion, suspected clinical features of KS may guide the diagnosis with comprehensive hormonal and imaging studies. However, the reported patient was diagnosed extremely late.

Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Persons: US Preventive Services Task Force Recommendation Statement.

Importance: Menopause is defined as the cessation of a person's menstrual cycle. It is defined retrospectively, 12 months after the final menstrual period. Perimenopause, or the menopausal transition, is the few-year time period preceding a person's final menstrual period and is characterized by increasing menstrual cycle length variability and periods of amenorrhea, and often symptoms such as vasomotor dysfunction. The prevalence and incidence of most chronic diseases (eg, cardiovascular disease, cancer, osteoporosis, and fracture) increase with age, and US persons who reach menopause are expected on average to live more than another 30 years. Objective: To update its 2017 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the benefits and harms of systemic (ie, oral or transdermal) hormone therapy for the prevention of chronic conditions in postmenopausal persons and whether outcomes vary by age or by timing of intervention after menopause. Population: Asymptomatic postmenopausal persons who are considering hormone therapy for the primary prevention of chronic medical conditions. Evidence Assessment: The USPSTF concludes with moderate certainty that the use of combined estrogen and progestin for the primary prevention of chronic conditions in postmenopausal persons with an intact uterus has no net benefit. The USPSTF concludes with moderate certainty that the use of estrogen alone for the primary prevention of chronic conditions in postmenopausal persons who have had a hysterectomy has no net benefit. Recommendation: The USPSTF recommends against the use of combined estrogen and progestin for the primary prevention of chronic conditions in postmenopausal persons. (D recommendation) The USPSTF recommends against the use of estrogen alone for the primary prevention of chronic conditions in postmenopausal persons who have had a hysterectomy. (D recommendation).

Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Persons: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: It is uncertain whether hormone therapy should be used for the primary prevention of chronic conditions such as heart disease, osteoporosis, or some types of cancers. Objective: To update evidence for the US Preventive Services Task Force on the benefits and harms of hormone therapy in reducing risks for chronic conditions. Data Sources: PubMed/MEDLINE, Cochrane Library, EMBASE, and trial registries from January 1, 2016, through October 12, 2021; surveillance through July 2022. Study Selection: English-language randomized clinical trials and prospective cohort studies of fair or good quality. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality; meta-analyses when at least 3 similar studies were available. Main Outcomes and Measures: Morbidity and mortality related to chronic conditions; health-related quality of life. Results: Twenty trials (N = 39 145) and 3 cohort studies (N = 1 155 410) were included. Participants using estrogen only compared with placebo had significantly lower risks for diabetes over 7.1 years (1050 vs 903 cases; 134 fewer [95% CI, 18-237]) and fractures over 7.2 years (1024 vs 1413 cases; 388 fewer [95% CI, 277-489]) per 10 000 persons. Risks per 10 000 persons were statistically significantly increased for gallbladder disease over 7.1 years (1113 vs 737 cases; 377 more [95% CI, 234-540]), stroke over 7.2 years (318 vs 239 cases; 79 more [95% CI, 15-159]), venous thromboembolism over 7.2 years (258 vs 181 cases; 77 more [95% CI, 19-153]), and urinary incontinence over 1 year (2331 vs 1446 cases; 885 more [95% CI, 659-1135]). Participants using estrogen plus progestin compared with placebo experienced significantly lower risks, per 10 000 persons, for colorectal cancer over 5.6 years (59 vs 93 cases; 34 fewer [95% CI, 9-51]), diabetes over 5.6 years (403 vs 482 cases; 78 fewer [95% CI, 15-133]), and fractures over 5 years (864 vs 1094 cases; 230 fewer [95% CI, 66-372]). Risks, per 10 000 persons, were significantly increased for invasive breast cancer (242 vs 191 cases; 51 more [95% CI, 6-106]), gallbladder disease (723 vs 463 cases; 260 more [95% CI, 169-364]), stroke (187 vs 135 cases; 52 more [95% CI, 12-104]), and venous thromboembolism (246 vs 126 cases; 120 more [95% CI, 68-185]) over 5.6 years; probable dementia (179 vs 91 cases; 88 more [95% CI, 15-212]) over 4.0 years; and urinary incontinence (1707 vs 1145 cases; 562 more [95% CI, 412-726]) over 1 year. Conclusions and Relevance: Use of hormone therapy in postmenopausal persons for the primary prevention of chronic conditions was associated with some benefits but also with an increased risk of harms.

From hormone replacement therapy to regenerative scaffolds: A review of current and novel primary hypothyroidism therapeutics.

Primary hypothyroidism severely impacts the quality of life of patients through a decrease in the production of the thyroid hormones T3 and T4, leading to symptoms affecting cardiovascular, neurological, cognitive, and metabolic function. The incidence rate of primary hypothyroidism is expected to increase in the near future, partially due to increasing survival of patients that have undergone radiotherapy for head and neck cancer, which induces this disease in over half of those treated. The current standard of care encompasses thyroid hormone replacement therapy, traditionally in the form of synthetic T4. However, there is mounting evidence that this is unable to restore thyroid hormone signaling in all tissues due to often persistent symptoms. Additional complications are also present in the form of dosage difficulties, extensive drug interactions and poor patience compliance. The alternative therapeutic approach employed in the past is combination therapy, which consists of administration of both T3 and T4, either synthetic or in the form of desiccated thyroid extract. Here, issues are present regarding the lack of regulation concerning formulation and lack of data regarding safety and efficacy of these treatment methods. Tissue engineering and regenerative medicine have been applied in conjunction with each other to restore function of various tissues. Recently, these techniques have been adapted for thyroid tissue, primarily through the fabrication of regenerative scaffolds. Those currently under investigation are composed of either biopolymers or native decellularized extracellular matrix (dECM) in conjunction with either primary thyrocytes or stem cells which have undergone directed thyroid differentiation. Multiple of these scaffolds have successfully restored an athyroid phenotype in vivo. However, further work is needed until clinical translation can be achieved. This is proposed in the form of exploration and combination of materials used to fabricate these scaffolds, the addition of peptides which can aid restoration of tissue homeostasis and additional in vivo experimentation providing data on safety and efficacy of these implants.

Relationship between the type of hormone replacement therapy and incidence of breast cancer in Korea.

OBJECTIVE: This study aimed to investigate the relationship between hormone replacement therapy (HRT) types and breast cancer (BC) incidence in postmenopausal women in Korea. METHODS: The nested case-control study used data from the National Health Insurance Service database. Among the women aged ≥50 years who menopaused between 2004 and 2007, BC incidence up to 2017 was analyzed in 36,446 women using or having used HRT for >1 year and in 36,446 women who did not use any HRT for more than 1 year. HRT types and duration were classified into three categories. RESULTS: BC risk (BCR) decreased with tibolone use for all ages. With HRT initiation in women aged ≥50 years, BCR was lower with tibolone and estrogen-progestogen therapy. HRT for <3 years showed lower BCR with tibolone, while higher BCR was observed with estrogen-only therapy. BCR was lower in women of all ages on HRT for >5 years than in the control group. CONCLUSIONS: For women in their 50s, tibolone use lowers BCR; for all ages, the use of any HRT for >5 years showed lower BCR in Korea. These divergent results from western countries could be associated with the specific characteristics of BC in Korea.

Long-term survival of nonlocalized epithelial ovarian cancer among women using menopausal hormone therapy prior to diagnosis: The extreme study.

Prediagnostic use of menopausal hormone therapy (MHT) has been suggested to be associated with improved survival of epithelial ovarian cancer (EOC). We investigated the potential long-term survival benefit of prediagnostic MHT use in women ≥50 years with nonlocalized EOC using the Extreme study including all women in Denmark registered with nonlocalized EOC during 2000 to 2014 (N = 3776). We obtained individual-level information on prediagnostic use of systemic estrogen therapy (ET) and estrogen plus progestin therapy (EPT) from the National Prescription Registry and estimated absolute and relative 5- and 10-year survival probabilities with 95% confidence intervals (CIs) using pseudo-values, taking into account histology, comorbidity, income and residual disease. Among women not having used prediagnostic MHT, 5- and 10-year absolute survival probabilities were 19% and 11%, respectively. Compared to MHT nonusers, prediagnostic systemic ET use for 3 to 4 years and ≥ 5 years was associated with 1.43 (95% CI: 1.01-2.02) and 1.22 (95% CI: 0.96-1.55) times higher 5-year survival probabilities, respectively. Ten-year survival probabilities were also increased but not statistically significantly. Among prediagnostic EPT users, increased 5-year (1.14, 95% CI: 0.85-1.53) and 10-year (1.38, 95% CI: 0.91-2.08) survival probabilities were observed after use for 3 to 4 years compared to MHT nonuse, whereas EPT use for ≥5 years was not associated with long-term survival of nonlocalized EOC. Our findings may suggest a better long-term survival of nonlocalized EOC in women having used long-term prediagnostic ET. However, the statistical precision of our results did not allow firm conclusions and more studies are needed.

Hormone therapy and Hypertension in Postmenopausal Women: Results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). / Terapia Hormonal e Hipertensão em Mulheres na Pós-Menopausa: Resultados do Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil).

BACKGROUND: Hypertension is a major risk factor for cardiovascular morbidity and mortality in post-menopausal women. Although menopausal hormone therapy (MHT) is a very effective treatment for vasomotor symptoms during this period, the influence of this therapy on blood pressure is not yet clear. OBJECTIVE: To evaluate the relationship between the use of MHT and hypertension in participants of the ELSA-Brasil. METHODS: A cross-sectional study using the baseline ELSA-Brasil data in a cohort of 2,138 women who had experienced natural menopause. This study analyzed hypertension, defined as arterial pressure ≥140/90 mmHg or previous antihypertensive use, and use of MHT, with participants being classified into never, past, and current users. Associations were assessed using an adjusted logistic regression model, with statistical significance set at p<0.05. RESULTS: Overall, 1,492 women (69.8%) had never used MHT, 457 (21.4%) had used it in the past, and 189 (8.8%) were current users. The use of MHT was more common in women who had a body mass index (BMI) <25 kg/m2and triglyceride levels <150 mg/dl, and who were physically less inactive, non-smokers, and non-diabetics. Current MHT users were less likely to have hypertension (OR=0.59; 95% CI: 0.41-0.85) compared to those who had never used MHT. In most cases, MHT was started at or before 59 years of age, within 10 years of becoming menopausal, and its use lasted for up to five years. CONCLUSION: Current MHT use was not related to hypertension, particularly in healthy women and in those under 60 years of age.

FUNDAMENTO: A hipertensão arterial é considerada um importante fator de risco de morbidade e mortalidade cardiovascular em mulheres na pós-menopausa. Embora a terapia hormonal da menopausa (THM) seja um tratamento muito eficiente para sintomas vasomotores nesse período, a influência dessa terapia na pressão arterial ainda não está clara. OBJETIVO: Avaliar a relação entre o uso de THM e a hipertensão em participantes do ELSA-Brasil. MÉTODOS: Um estudo transversal usando dados da linha de base da coorte ELSA-Brasil, com 2.138 mulheres que passaram por menopausa natural. Neste estudo, foi analisado a hipertensão, definida como pressão arterial ≥140/90 mmHg ou uso anterior de anti-hipertensivo, e o uso da THM, com participantes sendo classificadas em grupos daquelas que nunca usaram, que já usaram e que estavam em uso atual. As associações foram avaliadas usando-se um modelo de regressão logística multivariada com uma significância estatística definida em p<0,05. RESULTADOS: No total, 1.492 mulheres (69,8%) nunca tinham usado a THM, 457 (21,4%) tinham usado no passado, e 189 (8,8%) estavam em uso atual. O uso de THM foi mais comum em mulheres que tinham índice de massa corporal <25 kg/m2 e níveis de triglicérides <150 mg/dl, que eram fisicamente menos inativas, não fumantes e não diabéticas. As mulheres em uso atual da THM apresentaram menores chances de ter hipertensão (OR=0,59; IC 95%: 0,41-0,85), em comparação com as que nunca a usaram. Na maioria dos casos, a THM foi iniciada com idade até 59 anos, com menos de 10 anos de menopausa e o uso durou até cinco anos. CONCLUSÃO: O uso atual da THM não esteve relacionado à hipertensão, especialmente em mulheres saudáveis e que tinham menos de 60 anos de idade.

Approach to the Patient: Management of Pituitary Hormone Replacement Through Transition.

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.

Somatropin therapy in italian adults with growth hormone deficiency.

BACKGROUND: In adult population, Growth Hormone Deficiency (GHD) is a complex clinical condition with heterogeneity of causes and duration. Growth Hormone (GH) replacement therapy has beneficial effects entailing a chronic and expensive use. Therefore, entity, appropriateness and standardization of GHD treatment need to be accurately analysed. In Italy, the epidemiological surveillance on somatropin therapy is entrusted to the National Register of Growth Hormone Therapy (Registro Nazionale degli Assuntori dell'Ormone della Crescita-RNAOC) by the Italian Regulation, in accordance of which the RNAOC-database is collecting the notifications of somatropin prescriptions. METHODS: Aim of this study is to analyse data on somatropin-treated adult population communicated to the RNAOC by the specialist centres of 15 Italian regions and 2 autonomous provinces. RESULTS: From 2011 to 2019, the somatropin-treated adults were 970 with 4061 examinations (1.21 ± 0.33 visits/year). The diagnoses were: hypopituitarism (n = 579); hypophysectomy (n = 383); and congenital GHD (n = 3). Five subjects were addressed with diagnoses not included in the regulation. The starting posology of somatropin was 0.320 (± 0.212) mg/day, 0.292 (± 0.167) mg/day in male and 0.360 (± 0.258) in female patients, with 7 administrations/week in 70.31% of the prescriptions. The differences in posology by gender persisted at 10th year of the follow-up. Starting dosage was higher in patients diagnosed with adult GHD before the age of 30 (0.420 ± 0.225 mg/day), with a progressive decrease of the dosage during the follow-up. CONCLUSIONS: This is the first report on adult GH treatment, describing numbers, diagnoses, and pharmaceutical prescriptions associated to somatropin therapy in a large cohort of Italian GHD-adults.