The 2017 Women's Health Initiative study and use of hormone therapy: an emulated repeated cross-sectional study.

BACKGROUND: Hormone therapy (HT) use among menopausal women declined after negative information from the 2002 Women's Health Initiative (WHI) HT study. The 2017 post-intervention follow-up WHI study revealed that HT did not increase long-term mortality. However, studies on the effects of the updated WHI findings are lacking. Thus, we assessed the impact of the 2017 WHI findings on HT use in Taiwan. METHODS: We identified 1,869,050 women aged 50-60 years, between June and December 2017, from health insurance claims data to compare HT use in the 3 months preceding and following September 2017. To address the limitations associated with interval-censored data, we employed an emulated repeated cross-sectional design. Using logistic regression analysis, we evaluated the impact of the 2017 WHI study on menopausal symptom-related outpatient visits and HT use. In a scenario analysis, we examined the impact of the 2002 trial on HT use to validate our study design. RESULTS: Study participants' baseline characteristics before and after the 2017 WHI study were not significantly different. Logistic regressions demonstrated that the 2017 study had no significant effect on outpatient visits for menopause-related symptoms or HT use among women with outpatient visits. The scenario analysis confirmed the negative impact of the 2002 WHI trial on HT use. CONCLUSIONS: The 2017 WHI study did not demonstrate any impact on either menopause-related outpatient visits or HT use among middle-aged women in Taiwan. Our emulated cross-sectional study design may be employed in similar population-based policy intervention studies using interval-censored data.

Menopausal Hormone Therapy, an Ever-Present Topic: A Pilot Survey about Women's Experience and Medical Doctors' Approach.

Background and Objective: Menopause can be associated with many clinical manifestations: vasomotor symptoms, urogenital problems, and additional psychological disturbances, such as anxiety, mood changes, and sleep alterations. The prolonged lack of hormones also increases the risk of long-term consequences. Hormone Replacement Treatment (HRT) in menopause consists of the administration of estrogen, alone or associated to progesterone, to relieve these uncomfortable disturbances and to prevent the onset of other pathologic conditions. The aim of this study is to examine the prevalence of HRT use in a sample of menopausal women and their experience with menopause and HRT. This study also investigates the knowledge of general practitioners (GPs) and gynecologists about HRT and its prescription. Materials and Methods: We conducted a cross-sectional population survey on 126 women of 50-59 years in an industrial city in the North of Italy, Vercelli (Novara), in Eastern Piedmont. We also presented a questionnaire on the topic to 54 medical doctors (GPs and gynecologists) of the same area. Results: The prevalence of HRT use in our sample was 11.9%. In total, a good percentage of the users affirmed to be satisfied with HRT. Additionally, a minority of women reported being ideally against the use of replacement hormones, were advised against using HRT by doctors, and did not use it because of the fear of side effects. We found a positive association between patient education, health care attitude, and HRT usage. A significant number of women knew about HRT from the media, and most of them were not informed by a health professional. Despite this, the interviewed doctors considered their knowledge about HRT as 'good' and would recommend HRT: only 5.6% would not prescribe it. Conclusions: Our results highlight the need for information about HRT among patients and health professionals, along with the need for more effective communication, evaluation, and suggestion of treatment.

Association between serum uric acid and carotid atherosclerosis in elderly postmenopausal women: A hospital-based study.

BACKGROUND: Carotid atherosclerosis (CAS) is associated with increased cardiovascular risk and implicated in 20-30% of strokes. METHODS: 504 patients were included in this study. The detailed medical history and the results of physical examination, carotid ultrasound examination, and routine laboratory tests were collected. Logistic regression analyses were conducted to analyze the relationship between the SUA and the presence of carotid plaques. And the relationship between SUA and the progression of CAS was analyzed by multiple linear regression. The effect of hormone replacement therapy (HRT) on CAS has also be evaluated. RESULTS: 412 patients (81.7%) had carotid plaques of different sizes by carotid ultrasound examination. We found a positive association between the level of SUA and the probability of having carotid plaque by univariate logistic regression (OR: 2.01, 95% CI: 1.83-2.19, p = 0.003). At 2 years post-discharge, we found that 1 mg/dL increase in SUA levels was expected to 0.946% increase in plaque score and 0.026 cm increase in carotid intima-media thickness, separately. Moreover, patients treated by long-term HRT (≥5 years) had a lower level of SUA and blood lipid and the less change of plaque score and carotid intima-media thickness than patients without HRT. CONCLUSION: The presence and progression of CAS had significantly positive associations with the level of SUA. And the HRT may have the ability to prevent the presence and progression of CAS. However, the safety and long-term outcome of HRT on CAS should be evaluated in further studies.

Association between menopausal hormone therapy, mammographic density and breast cancer risk: results from the E3N cohort study.

BACKGROUND: Menopausal hormone therapy (MHT) is a risk factor for breast cancer (BC). Evidence suggests that its effect on BC risk could be partly mediated by mammographic density. The aim of this study was to investigate the relationship between MHT, mammographic density and BC risk using data from a prospective study. METHODS: We used data from a case-control study nested within the French cohort E3N including 453 cases and 453 matched controls. Measures of mammographic density, history of MHT use during follow-up and information on potential confounders were available for all women. The association between MHT and mammographic density was evaluated by linear regression models. We applied mediation modelling techniques to estimate, under the hypothesis of a causal model, the proportion of the effect of MHT on BC risk mediated by percent mammographic density (PMD) for BC overall and by hormone receptor status. RESULTS: Among MHT users, 4.2% used exclusively oestrogen alone compared with 68.3% who used exclusively oestrogens plus progestogens. Mammographic density was higher in current users (for a 60-year-old woman, mean PMD 33%; 95% CI 31 to 35%) than in past (29%; 27 to 31%) and never users (24%; 22 to 26%). No statistically significant association was observed between duration of MHT and mammographic density. In past MHT users, mammographic density was negatively associated with time since last use; values similar to those of never users were observed in women who had stopped MHT at least 8 years earlier. The odds ratio of BC for current versus never MHT users, adjusted for age, year of birth, menopausal status at baseline and BMI, was 1.67 (95% CI, 1.04 to 2.68). The proportion of effect mediated by PMD was 34% for any BC and became 48% when the correlation between BMI and PMD was accounted for. These effects were limited to hormone receptor-positive BC. CONCLUSIONS: Our results suggest that, under a causal model, nearly half of the effect of MHT on hormone receptor-positive BC risk is mediated by mammographic density, which appears to be modified by MHT for up to 8 years after MHT termination.

Weight gain and obesity rates in transgender and gender-diverse adults before and during hormone therapy.

BACKGROUND: Obesity rates and weight changes in adults on gender-affirming hormone therapy are lacking or limited by small sample sizes, duration, and location. SUBJECTS/METHODS: This longitudinal study followed the body mass index and body weights of 470 transgender and gender-diverse adult patients (247 transfeminine and 223 transmasculine; mean age, 27.8 years) seen at a Federally Qualified Health Center and an academic endocrinology practice, both in Washington DC USA. Body weight and body mass index were recorded at baseline and at multiple follow-up clinical visits up to 57 months after the initiation of gender-affirming hormone therapy. The outcomes of this study were the changes to body weight and obesity rates following hormone therapy. RESULTS: Within 2-4 months of starting gender-affirming hormone therapy, the mean body weight increased in the transmasculine group by 2.35 (1.15-3.55) kg and further increased beyond 34 months. Among the transfeminine group, the mean body weight was stable for the first 21 months of hormone therapy and then began to steadily increase, particularly in those under 30 years old. The prevalence of obesity at baseline was 25% in the transfeminine group and 39% in the transmasculine group. Following the initiation of hormone therapy, rates of obesity ranged from 42 to 52% among the transmasculine group and 21 to 30% among transfeminine group. Following 11-21 months of hormone therapy, weight gain ≥5 kg was seen among 21% of transfeminine individuals and 30% of transmasculine individuals. CONCLUSIONS: As compared with transfeminine individuals, transmasculine individuals have greater rates of obesity and weight gain before and during hormone therapy. Body weight and body mass index should be routinely monitored before and after the initiation of gender-affirming hormone therapy. Multidisciplinary weight-reduction interventions should be promoted where appropriate.

A Danish nationwide study of risk factors associated with Type I and Type II endometrial cancer.

OBJECTIVE: To examine risk factors for Type I and Type II endometrial cancer (EC) and to directly compare the influence of risk factors for Type II with Type I tumors. Furthermore, to examine whether risk factors for high-grade Type I and Type II tumors differed from low-grade Type I tumors. METHODS: Women with EC diagnosed during 2000-2016 were identified in the Danish Cancer Registry. A case-control analysis was conducted with 1:15 random population controls matched on age and gender. Using conditional logistic regression, odds ratios and 95% confidence intervals on risk factors for Type I and II tumors were estimated. In case-case analyses, risk factors were evaluated in a direct comparison of cases grouped by tumor type and grade. RESULTS: We identified 6958 women with Type I EC and 1206 women with Type II EC. In the case-control analysis, nulliparity and diabetes were associated with increased risk of both tumor types, whereas hormone replacement therapy only increased the risk of Type I EC. When directly comparing Type I and II tumors, the influence of BMI ≥ 30, current smoking, and parity ≥ 3 was strongest for Type I EC. The associations for the majority of risk factors were similar for Type II and high-grade Type I tumors compared with low-grade Type II tumors. CONCLUSIONS: Risk factors for Type I and II tumors were overlapping suggesting that Type II tumors may be less estrogen-independent than previously anticipated. High-grade Type I tumors seemed to resemble Type II tumors more than low-grade Type I tumors.

Reproductive functions and fertility preservation in transgender women: a French case series.

RESEARCH QUESTION: The reproductive potential of transgender people may be impaired by gender-affirming hormone treatment (GAHT) and is obviously suppressed by gender-affirming surgery involving bilateral orchiectomy. The evolution of medical support for transgender people has made fertility preservation strategies possible. Fertility preservation in transgender women mainly relies on sperm cryopreservation. There are few studies on this subject, and the sample sizes are small, and so it difficult to know whether fertility preservation procedures are feasible and effective in trans women. DESIGN: This retrospective study reports the management of fertility preservation in transgender women referred to the study centre for sperm cryopreservation, and the semen parameters of trans women were compared with those of sperm donors. RESULTS: Ninety-six per cent of transgender women who had not started treatment benefitted from sperm cryopreservation, compared with 80% of those who attempted a therapeutic window and 50% of those receiving hormonal treatment at the time of sperm collection. No major impairment of semen parameters was observed in transgender women who had not started GAHT compared with sperm donors. However, even though the frequency of oligozoospermia was no different, two transgender women presented azoospermia. Some transgender women who had started GAHT could benefit from sperm freezing. None of them were treated with gonadotrophin-releasing hormone (GnRH) analogues. CONCLUSIONS: Parenthood strategies for transgender people have long been ignored, but this is an important issue to consider, especially because medical treatments and surgeries may be undertaken in adolescents or very young adults. Fertility preservation should ideally be offered prior to initiation of GAHT.

Comparison of Dosing Schemes for Thyroid Hormone Replacement Therapy After Thyroidectomy.

BACKGROUND: Current thyroid hormone replacement therapy (THRT) is built on weight-based standard calculation of dose. A novel Poisson regression model, which accounts for seven clinical variables, was recently proposed to improve accuracy of THRT. We aimed to compare the accuracy of estimated THRT dose to reach euthyroid and the difference in predicted dose between the Poisson (scheme A) and the weight-based standard (scheme B) in patients following total thyroidectomy for benign disease. METHODS: We retrospectively reviewed medical record of patients who underwent total or completion thyroidectomy for benign disease at a single institution between 2011 and 2019. The THRT dose was calculated using both schemes. We compared the difference between calculated THRT and prediction rates for optimal THRT dosing needed to achieve a euthyroid state between dosing schemes. Patients were evaluated for achieving euthyroid state, defined as TSH 0.45-4.5 mIU/L. We also compared dosing error rates (> 25 mcg over- and underdosing) between schemes. Prediction rates were compared by BMI tertiles to account for the effect of BMI extremes in achieving euthyroid state. The difference in predicted dose between schemes was calculated in both the total sample size and patients that met euthyroid. A measure of agreement, Kappa, was used to estimate agreement between dosing schemes. RESULTS: A total of 406 patients underwent total thyroidectomy for benign disease, with 184 having sufficient follow up data confirming euthyroid state. Of the 184 patients, 85.9% (n = 158) were women, 81% (n = 149) were Hispanic, and 56.5% (n = 104) were obese with a median BMI of 30.8 kg/m2. Scheme A resulted in a higher, but not statistically significant, accuracy rate (A: 60.3%, n = 111 versus B: 53.8%, n = 99; P = 0.21). Overdosing errors were lower with Scheme A (A:17.9% versus B: 32.1%; P = 0.0025) and less extreme > 25 µg (A: 17.9% versus B: 26.1%; P = 0.08). A trend in improved accuracy in patients with a BMI > 35 kg/m2 was noted (A: 46.9% versus B: 34.4%; P = 0.20). Scheme A also resulted in less overdosing errors in obese patients compared to Scheme B (A: 19.2% versus 45.2%; P = 0.0006). The average difference in predicted dose between schemes was an entire dose difference, mean of 16.0 µg and 15.8 µg for the total and euthyroid samples respectively. Furthermore, for the majority of patients the predicted dose did not match between the two dosing schemes for total and euthyroid samples, 76% (n = 311) and 76% (n = 141) respectively. In patients that achieved euthyroid, agreement between dosing schemes was low to moderate (Kappa = 0.360). CONCLUSIONS: Lower rates of overdosing were found for scheme A, particularly with obese patients. No statistically significant differences in predicted THRT dose was observed between schemes. The difference in predicted dose between schemes was on average 15 ug, correlating with an entire dose. The consideration of clinical variables other than weight (scheme A) when determining optimal THRT dosing may be of importance to prevent overdoses, with particular clinical relevance in patients with higher BMIs.

Use of thyroid hormones in hypothyroid and euthyroid patients: A 2020 THESIS questionnaire survey of members of the Danish Endocrine Society.

PURPOSE: The standard treatment of hypothyroidism is levothyroxine (LT4), which is available as tablets or soft-gel capsules in Denmark. This study aimed to investigate Danish endocrinologists' use of thyroid hormones in hypothyroid and euthyroid patients. METHODS: An e-mail with an invitation to participate in an online survey investigating practices about substitution with thyroid hormones was sent to all members of the Danish Endocrine Society (DES). RESULTS: Out of 488 eligible DES members, a total of 152 (31.2%) respondents were included in the analysis. The majority (94.1%) of responding DES members use LT4 as the treatment of choice. Other treatment options for hypothyroidism are also used, as 58.6% prescribe combination therapy with liothyronine (LT3) + LT4 in their clinical practice. LT4 + LT3 combination is preferred in patients with persistent symptoms of hypothyroidism despite biochemical euthyroidism on LT4 treatment. Over half of the respondents answered that thyroid hormone therapy is never indicated for euthyroid patients, but 42.1% will consider it for euthyroid infertile women with high antibody levels. In various conditions that could interfere with the absorption of LT4, most responding Danish endocrinologists prefer tablets and do not expect a significant difference when switching from one type of tablet formulation to another. CONCLUSION: The treatment of choice for hypothyroidism is LT4. Combination therapy with LT4 + LT3 is considered for patients with persistent symptoms. Even in the presence of conditions affecting bioavailability, responding Danish endocrinologists prefer LT4 tablets rather than newer LT4 formulations, such as soft-gel capsules.

Menopausal hormone therapy treatment options and ovarian cancer risk: A Swedish prospective population-based matched-cohort study.

Although menopausal hormone therapy (MHT) seemingly increases the risk of ovarian cancer, evidence is insufficient whether the risk varies between various MHT formulations, regimens and administration modes. With the aim of filling these knowledge gaps, we investigated the effect of different MHT treatment options on the risk of ovarian cancer. This prospective Swedish population-based matched-cohort study included all women ≥40 years having used systemic MHT between 2005 and 2012 (288,950 ever-users), group-level matched (1:3) to 866,546 nonusers. MHT use was ascertained from the Swedish Prescribed Drug Registry and data was linked to several national health data registries. Multivariable conditional logistic regression provided odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for parity, and comorbidities. Current EP-MHT use was associated with a modestly increased risk of ovarian cancer (OR = 1.38, 95% CI 1.18-1.62), while no consistent risk was found among past users (OR = 1.00, 95% CI 0.84-1.18). Current continuous testosterone derived (OR = 1.50, 95% CI 1.15-1.96) regimens increased the risk whereas progesterone derived (OR = 1.48, 95% CI 1.00-2.21) regimens increased the risk marginally. Nonsignificant positive associations were observed for sequential regimens (OR = 1.87, 95% CI 0.70-5.08; OR = 1.54, 95% CI 0.96-2.47, respectively). An inverse relationship was observed for all E-MHT use (OR = 0.25, 95% CI 0.22-0.29), but this association might partly be explained by underreporting of oophorectomies or tubal ligations. Current cutaneous EP-MHT (OR = 1.28, 95% CI 0.81-2.02) suggested a possibly lower risk than oral MHT (OR = 1.48, 95% CI 1.25-1.75). In conclusion EP-MHT, notably continuous regimens, were associated with a modestly increased risk of ovarian cancer. The role of E-MHT requires further clarification.

Hormone replacement therapy and mammographic density: a systematic literature review.

PURPOSE: Hormone replacement therapy (HRT) is used to reduce climacteric symptoms of menopause and prevent osteoporosis; however, it increases risk of breast cancer. Mammographic density (MD) is also a strong risk factor for breast cancer. We conducted this review to investigate the association between HRT use and MD and to assess the effect of different HRT regimens on MD. METHODS: Two of authors examined articles published between 2002 and 2019 from PubMed, Embase, and OVID using Covidence systematic review platform. Any disagreements were discussed until consensus was reached. The protocol used in this review was created in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Quality of each eligible study was assessed using the Oxford Center for Evidence-Based Medicine (OCEBM) hierarchy. RESULTS: Twenty-two studies met the inclusion criteria. Six studies showed that using estrogen plus progestin (E + P) HRT was associated with higher MD than estrogen alone. Four studies reported that continuous estrogen plus progestin (CEP) users had higher MD than sequential estrogen plus progestin (SEP) and estrogen alone users. However, two studies showed that SEP users had slightly higher MD than CEP users and estrogen alone users. CONCLUSIONS: Epidemiological evidence is rather consistent suggesting that there is a positive association between HRT use and MD with the highest increase in MD among current users, and CEP users. Our results suggest that due to increase in MD and masking effect, current E + P users may require additional screening procedures, shorter screening intervals, or using advanced imaging techniques.

The prevalence and demographic determinants of blood donors receiving testosterone replacement therapy at a large USA blood service organization.

BACKGROUND: Blood donors receiving testosterone replacement therapy (TRT) often require therapeutic phlebotomy due to erythrocytosis. Red blood cells (RBCs) donated by eligible TRT donors are approved for collection and transfusion. This study was aimed at defining the prevalence and demographic determinants of TRT donors at a large USA blood service organization. STUDY DESIGN: Donation data from TRT donors and matched controls was collected from a de-identified electronic donor database across 16 blood centers in 2017-2018. Demographic determinants included race, sex, age, hemoglobin (Hb), body mass index (BMI), mean arterial pressure (MAP), and the frequency of donations in the 2-year period. RESULTS: TRT donors comprised 1.6% of the donor population and produced 2.2% of RBC units during 2018. TRT donors were likely to be middle-aged white or Hispanic men, with high prevalence of obesity (50.8% of TRT donors had BMI ≥30 kg/m2 compared with 36.2% in controls) and intensive donation frequency (1 to 29 donations in 2 years vs. 1 to 12 in controls). TRT donors had significantly (p < 0.0001) higher MAP and Hb compared with controls (MAP 99.9 ± 9.81 vs. 96.5 ± 10.1 mmHg; Hb 17.8 ± 1.44 vs. 15.6 ± 1.37 g/dL). One year of donations was associated with significant decreases in MAP and Hb for TRT donors. CONCLUSIONS: TRT is associated with high prevalence of erythrocytosis and obesity that may explain the intensive donation frequency, high MAP, and Hb. Frequent phlebotomies had a moderately positive effect on blood pressure and Hb levels. Potential implications of TRT on the quality of the RBC products require further evaluation.

Menopausal hormone therapy prior to the diagnosis of ovarian cancer is associated with improved survival.

PURPOSE: Prior studies of menopausal hormone therapy (MHT) and ovarian cancer survival have been limited by lack of hormone regimen detail and insufficient sample sizes. To address these limitations, a comprehensive analysis of 6419 post-menopausal women with pathologically confirmed ovarian carcinoma was conducted to examine the association between MHT use prior to diagnosis and survival. METHODS: Data from 15 studies in the Ovarian Cancer Association Consortium were included. MHT use was examined by type (estrogen-only (ET) or estrogen+progestin (EPT)), duration, and recency of use relative to diagnosis. Cox proportional hazards models were used to estimate the association between hormone therapy use and survival. Logistic regression and mediation analysis was used to explore the relationship between MHT use and residual disease following debulking surgery. RESULTS: Use of ET or EPT for at least five years prior to diagnosis was associated with better ovarian cancer survival (hazard ratio, 0.80; 95% CI, 0.74 to 0.87). Among women with advanced stage, high-grade serous carcinoma, those who used MHT were less likely to have any macroscopic residual disease at the time of primary debulking surgery (p for trend <0.01 for duration of MHT use). Residual disease mediated some (17%) of the relationship between MHT and survival. CONCLUSIONS: Pre-diagnosis MHT use for 5+ years was a favorable prognostic factor for women with ovarian cancer. This large study is consistent with prior smaller studies, and further work is needed to understand the underlying mechanism.

Use of antidepressants in women after prophylactic bilateral oophorectomy: A Danish national cohort study.

OBJECTIVE: To investigate the association between prophylactic bilateral oophorectomy and use of antidepressants in women with a family history of cancer. METHODS: Nationwide population-based cohort study using Danish National Registries including women oophorectomized due to a family history of cancer (n = 2,002) and an age matched reference group (n = 18,018). Analyses were stratified by age at time of bilateral oophorectomy and use of hormone replacement therapy (HRT). RESULTS: Women oophorectomized at age ≤ 45 years were more likely to use antidepressants from the first year after bilateral oophorectomy (OR = 1.34; 95 % CI: 1.08-1.65) compared to the reference group. Women oophorectomized at age 46-55 years and at age >55 years had no significantly increased use of antidepressants (OR = 0.90; 95 % CI: 0.68-1.18 and OR = 1.14; 95 % CI: 0.81-1.61). The increased use of antidepressants in women oophorectomized at age ≤ 45 years was limited to women treated with HRT (OR = 1.51; 95 % CI: 1.18-1.94) whereas women oophorectomized at age ≤ 45 years not treated with HRT had no increased use of antidepressants (OR = 1.03; 95 % CI: 0.70-1.51). CONCLUSIONS: Women oophorectomized due to a family history of cancer at age ≤ 45 years were more likely to use antidepressants after bilateral oophorectomy. The increased use of antidepressants was limited to women treated with HRT. The study calls for further large-scale studies to understand how bilateral oophorectomy and concomitant HRT affects risk of depression in women with a family history of cancer.

Insurance Coverage and Use of Hormones Among Transgender Respondents to a National Survey.

PURPOSE: We undertook a study to assess the associations between barriers to insurance coverage for gender-affirming hormones (either lack of insurance or claim denial) and patterns of hormone use among transgender adults. METHODS: We used data from the US Transgender Survey, a large national sample of 27,715 transgender adults, collected from August to September 2015. We calculated weighted proportions and performed multivariate logistic regression analyses. RESULTS: Of 12,037 transgender adults using hormones, 992 (9.17%) were using nonprescription hormones. Among insured respondents, 2,528 (20.81%) reported that their claims were denied. Use of nonprescription hormones was more common among respondents who were uninsured (odds ratio = 2.64; 95% CI, 1.88-3.71; P <.001) or whose claims were denied (odds ratio = 2.53; 95% CI, 1.61-3.97; P <.001). Uninsured respondents were also less likely to be using hormones (odds ratio = 0.37; 95% CI, 0.24-0.56; P <.001). CONCLUSIONS: Lack of insurance coverage for gender-affirming hormones is associated with lower overall odds of hormone use and higher odds of use of nonprescription hormones; such barriers may thus be linked to unmonitored and unsafe medication use, and increase the risks for adverse health outcomes. Ensuring access to hormones can decrease the economic burden transgender people face, and is an important part of harm-reduction strategies.

Adherence to treatment in children with growth hormone deficiency, small for gestational age and Turner syndrome in Mexico: results of the Easypod™ connect observational study (ECOS).

BACKGROUND: Assessing adherence to growth hormone (GH) is challenging. The Easypod™ connect device delivers pre-set doses of recombinant human GH (r-hGH) and stores a digital record of adherence that can be shared with healthcare provider. We assessed adherence to r-hGH delivered with Easypod™ according to the approved pediatric indications for r-hGH: growth hormone deficiency (GHD), born small for gestational age (SGA) who failed to show catch-up growth and Turner syndrome (TS). METHODS: ECOS (NCT01555528) was a multicenter (24 countries), 5-year, longitudinal, observational study, which aimed to evaluate country-specific adherence to r-hGH therapy prescribed via the Easypod™ electronic injection device. The primary endpoint was yearly adherence. Secondary endpoints were height velocity, height velocity standard deviation scores (SDS), height, height SDS and IGF-1 concentrations. Clinical and auxological data were obtained from medical records and adherence from Easypod™ logs. RESULTS: This study included 147 Easypod™-naïve Mexican children assessed during 3 years (mean age: 9.96 ± 3.41 years, 56.8% boys, mean height SDS at baseline: - 2.17 ± 0.97): 118 with GHD, 24 SGA and 5 with TS. A total of 105 (71.4%) patients were GH naïve. Overall median adherence was > 90% over the first year of treatment and > 80% at 3 years. Adherence was not different by r-hGH indication or between GH-naïve or experienced patients. At 1-year follow-up, mean change in height SDS was 0.57 ± 0.34, whereas mean height velocity SDS was 2.85 ± 2.51. In all, 84.7% patients had normal IGF-1 concentrations at 1-year follow-up. Adherence was associated with change in height SDS (r = 0.239, p = 0.005) and height velocity SDS (r = 0.194, p = 0.027). CONCLUSION: Adherence rates with the Easypod™ device are high and maintained over time in GHD, SGA and TS Easypod™-naïve Mexican patients. High adherence is associated with better outcomes. Easypod™ assists physicians in monitoring adherence to r-hGH.

Lung cancer incidence and mortality in relationship to hormone replacement therapy use among women participating in the PLCO trial: a post hoc analysis.

OBJECTIVE: To evaluate the impact of hormone replacement therapy (HRT) on the incidence and mortality of lung cancer among female participants in the prostate, lung, colorectal, and ovary (PLCO) trial. METHODS: All women participating in the PLCO trial with complete information about HRT exposure were included in the current analysis. All study population were aged 55-74 years without prior history of lung cancer at the time of study enrollment. Multivariate Cox regression analysis was used to evaluate the impact of HRT exposure on lung cancer incidence and mortality. For both end points, the model was adjusted for: age, body mass index, study arm, race, cigarette smoking and family history of lung cancer. RESULTS: A total of 77,911 female participants were included in the current analysis, including 27,663 participants who never used HRT before inclusion into the PLCO trial and 50,248 participants who used some form of HRT before inclusion into the PLCO trial. Prior exposure to HRT seems to be protective against the development of lung cancer in a multivariate analysis (hazard ratio for ever exposure versus never exposure 0.876; 95% CI 0.783-0.981; P = 0.022). Similarly, prior exposure to HRT seems also to be protective against death from lung cancer in a multivariate analysis (hazard ratio for ever exposure versus never exposure 0.814; 0.709-0.934; P = 0.003). Further multivariate Cox regression analysis showed that current HRT usage at the time of PLCO trial entry (and not former HRT usage) seemed to be protective against lung cancer development (hazard ratio for current versus never users 0.842; 0.743-0.954; P = 0.007) and lung cancer-specific mortality (hazard ratio for current versus never users 0.800; 0.686-0.932; P = 0.004). CONCLUSION: HRT use at the time of PLCO trial entry seems to be associated with lower probability of lung cancer development and death. Further studies are needed to elucidate the biological mechanisms behind this observation.

Levothyroxine in the treatment of overt or subclinical hypothyroidism: a systematic review and meta-analysis.

The goal of this study was to review relevant randomized controlled trials in order to determine the clinical efficacy of levothyroxine in the treatment of overt or subclinical hypothyroidism. Using appropriate keywords, we identified relevant studies using PubMed, the Cochrane library, and Embase. Key pertinent sources in the literature were also reviewed, and all articles published through December 2019 were considered for inclusion. For each study, we assessed odds ratios (ORs), mean difference (MD), and 95% confidence interval (95%CI) to assess and synthesize outcomes. We included 25 studies with totally 1,735 patients in the meta-analysis. In the patients with hypothyroidism, compared with L-T4, L-T4 plus L-T3 significantly decreased TSH levels and increased FT3 levels. Compared with placebo, L-T4 significantly increased FT4 levels and decreased TSH levels. In patients with subclinical hypothyroidism, compared with placebo, L-T4 significantly decreased SBP, TSH, T3 and TC and increased FT3 and FT4.

Hormone Replacement Therapy Prescription after Premature Surgical Menopause.

STUDY OBJECTIVE: To assess hormone replacement therapy (HRT) prescription pattern in patients undergoing premature surgical menopause on the basis of surgical indication. DESIGN: Retrospective cohort study. SETTING: Academic tertiary care center. PATIENTS: Surgically menopausal patients aged ≤45 years who underwent a minimally invasive hysterectomy with salpingo-oophorectomy. INTERVENTIONS: HRT prescription in the 6-week postoperative period. MEASUREMENTS AND MAIN RESULTS: A total of 63 patients met inclusion criteria. Of these, 52% (n = 33) were prescribed HRT in the 6-week postoperative period. Indications for surgical menopause included pelvic pain or endometriosis (31.7%), gynecologic malignancy (20.6%), BRCA gene mutation (17.4%), breast cancer (9.5%), Lynch syndrome (4.8%), and other (15.8%). In total, 80% of patients with pelvic pain, 25% with gynecologic malignancies, 45% with BRCA gene mutations, 33.3% with breast cancer, and 66.6% with Lynch syndrome used HRT postoperatively. In patients who used HRT postoperatively, 76% were offered preoperative HRT counseling. This is in contrast with those patients who did not use HRT postoperatively, of whom only 33% were offered HRT counseling (p <.001). Perioperative complications were not predictive of HRT use postoperatively. In patients who did not use HRT postoperatively, 13.3% used alternative nonhormonal therapy. CONCLUSION: In patients who underwent premature surgical menopause, 52% used HRT postoperatively. Patients with pelvic pain and Lynch syndrome were more likely to use HRT, whereas those with gynecologic or breast malignancies and BRCA gene mutations were less likely to use HRT. Preoperative HRT counseling was associated with postoperative HRT use.

Hormone Therapy and Discrimination in the Labor Market: Emerging Experimental Evidence on the Economics of Endocrinology.

BACKGROUND: Gender transitioning is increasingly common, but little is known about the extent to which individuals in transition and fully transitioned suffer from wage discrimination. Methods: Managers in the United States (n=204) were shown photos of white and Asian male and female "employees" at different stages of simulated hormone therapy and were asked to estimate their actual hourly wages based on appearance. RESULTS: The results suggest that Asian men and women "in transition" and fully transitioned do not suffer from significant wage discrimination. However, among the white stimuli, gender atypical ("in transition" and fully transitioned) men and women are estimated to earn significantly less than their gender typical (sexually dimorphic) counterparts, with some gender-specific nuances. CONCLUSIONS: The effects of hormone therapy may have a deleterious impact on the wages of white transgender individuals.