Abstract
Context
A novel formulation of oral testosterone (T) undecanoate (TU) was evaluated in a phase 3 clinical trial.
Objective
Determine efficacy, short-term safety, and alignment of new oral TU ...formulation with current US approval standards for T replacement therapy.
Design
Randomized, active-controlled, open-label study.
Setting and Patients
Academic and private clinical practice sites; enrolled patients were clinically hypogonadal men 18 to 65 years old.
Methods
Patients were randomized 3:1 to oral TU, as prescribed (JATENZO®; n = 166) or a topical T product once daily (Axiron®; n = 56) for 3 to 4 months. Dose titration was based on average T levels (Cavg) calculated from serial pharmacokinetic (PK) samples. T was assayed by liquid chromatography–mass spectrometry/mass spectrometry. Patients had 2 dose adjustment opportunities prior to final PK visit. Safety was assessed by standard clinical measures, including ambulatory blood pressure (BP).
Results
87% of patients in both groups achieved mean T Cavg in the eugonadal range. Sodium fluoride-ethylenediamine tetra-acetate plasma T Cavg (mean ± standard deviation) for the oral TU group was 403 ± 128 ng/dL (~14 ± 4 nmol/L); serum T equivalent, ~489 ± 155 ng/dL (17 ± 5 nmol/L); and topical T, 391 ± 140 ng/dL (~14 ± 5 nmol/L). Modeling/simulation of T PK data demonstrated that dose titration based on a single blood sample 4 to 6 h after oral TU dose yielded efficacy (93%) equivalent to Cavg-based titration (87%). Safety profiles were similar in both groups, but oral TU was associated with a mean increase in systolic BP of 3 to 5 mm Hg.
Conclusion
A new oral TU formulation effectively restored T to mid-eugonadal levels in hypogonadal patients.
Estrogen, Estrogen Receptor and Lung Cancer Hsu, Li-Han; Chu, Nei-Min; Kao, Shu-Huei
International journal of molecular sciences,
08/2017, Letnik:
18, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Estrogen has been postulated as a contributor for lung cancer development and progression. We reviewed the current knowledge about the expression and prognostic implications of the estrogen receptors ...(ER) in lung cancer, the effect and signaling pathway of estrogen on lung cancer, the hormone replacement therapy and lung cancer risk and survival, the mechanistic relationship between the ER and the epidermal growth factor receptor (EGFR), and the relevant clinical trials combining the ER antagonist and the EGFR antagonist, to investigate the role of estrogen in lung cancer. Estrogen and its receptor have the potential to become a prognosticator and a therapeutic target in lung cancer. On the other hand, tobacco smoking aggravates the effect of estrogen and endocrine disruptive chemicals from the environment targeting ER may well contribute to the lung carcinogenesis. They have gradually become important issues in the course of preventive medicine.
The incidence of pancreatic cancer is leveling between sexes. Smoking, high age and heredity are established risk factors, but evidence regarding the influence of hormonal factors is unclear. In this ...study, we investigated the associations of reproductive factors, use of oral contraceptives (OC) and hormone replacement therapy (HRT) with pancreatic cancer risk in the Malmö Diet and Cancer Study, a prospective, population‐based cohort encompassing 17,035 women. Up until 31 December 2015, 110 women were identified with incident pancreatic cancer through the Swedish Cancer Registry. Higher age at menarche was significantly associated with pancreatic cancer risk (age‐adjusted hazard ratio HR = 1.17; 95% confidence interval CI 1.04–1.32, and fully adjusted HR = 1.17; 95% CI 1.04–1.32). Ever use of OC was not significantly associated with pancreatic cancer risk but ever use of HRT was significantly associated with a decreased risk of pancreatic cancer (age‐adjusted HR = 0.47, 95% CI 0.23–0.97, and fully adjusted HR = 0.48, 95% CI 0.23–1.00), in particular use of estrogen‐only regimen (age‐adjusted HR = 0.21; 95% CI 0.05–0.87 and fully adjusted HR = 0.22; 95% CI 0.05–0.90). Age at menopause or first childbirth, parity and breastfeeding history were not significantly associated with pancreatic cancer risk. Collectively, these findings suggest a protective role of female hormones against pancreatic cancer. Further studies are needed, and potential modifying genetic factors and indirect hazardous effects of smoking should also be considered.
What's new?
Female hormones appear to protect against pancreatic cancer, at least in Sweden. Numerous studies have investigated the relationship between the two, but no clear picture has yet emerged. These authors used data from the Malmö Diet and Cancer study, looking for correlations between hormone levels and cancer risk. They found that a younger start to menstruation—indicating an earlier boost in estrogen—correlated with less chance of developing pancreatic cancer. Use of hormone replacement therapy, particularly estrogen‐only therapy, significantly reduced risk among postmenopausal women. Breastfeeding, oral contraceptive use and parity did not appear to affect pancreatic cancer risk.
Hypothyroidism in Pregnancy Taylor, Peter N; Lazarus, John H
Endocrinology and metabolism clinics of North America,
09/2019, Letnik:
48, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Thyroid hormone is essential for pregnancy and ensuring fetal development. Pregnancy also places substantial demands on the thyroid axis. Overt hypothyroidism is associated with substantial adverse ...obstetric and offspring outcomes and requires treatment. Borderline thyroid dysfunction is common in women and associated with adverse obstetric and offspring outcomes, although benefits of screening for and treating borderline thyroid function are unclear. Many women are established on thyroid hormone replacement before pregnancy and doses need increasing during pregnancy. Care is taken to prevent overreplacement. Universal thyroid screening in pregnancy is being undertaken in several countries, although it remains a matter of debate.
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.
What's new?
While menopausal hormone therapy (MHT) appears to influence ovarian cancer risk, whether the risk varies between various MHT treatment options remains unknown. In this Swedish population‐based matched‐cohort study, including all MHT receivers during 2005–2012, we found notable differences between MHT regimens. In addition, cutaneous EP‐MHT suggested for less risk than the most commonly prescribed oral MHT. These findings are important for choosing a MHT treatment option, which involves less excess ovarian cancer risk.
Context:
Testosterone's effects on muscle strength and physical function in older men have been inconsistent; its effects on muscle power and fatigability have not been studied.
Objective:
To ...determine the effects of testosterone administration for 3 years in older men on muscle strength, power, fatigability and physical function
Study Design:
In this double-blind, placebo-controlled, randomized trial, healthy men ≥60 years with total testosterone 100–400 ng/dL or free testosterone <50 pg/mL, were randomized to 7.5-g 1% testosterone or placebo gel daily for 3 years.
Outcomes:
Loaded and unloaded stair-climbing power, muscle strength, power, and fatigability in leg press and chest press exercises, and lean mass at baseline, 6, 18, and 36 months.
Results:
The groups were similar at baseline. Testosterone administration for 3 years was associated with significantly greater performance in unloaded and loaded stair-climbing power than placebo (mean (95% CI) estimated between-group difference 10.7W (-4.0,25.5; P=0.026) and 22.4W (4.6,40.3) P=0.027), respectively. Changes in chest press strength (estimated mean difference 16.3N (95% CI 5.5,27.1; P<0.001) and power (mean (95%CI) difference 22.5W (7.5,37.5); P<0.001), and leg press power were significantly greater in men randomized to testosterone than in those randomized to placebo. Lean body mass significantly increased more in the testosterone group.
Conclusion:
Compared to placebo, testosterone replacement in older men for 3 years was associated with modest but significantly greater improvements in stair-climbing power, muscle mass and power. Clinical meaningfulness of these treatment effects and their impact on disability in older adults with functional limitations remains to be studied.
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