Nanostructured transdermal hormone replacement therapy for relieving menopausal symptoms: a confocal Raman spectroscopy study

OBJECTIVE: To determine the safety and efficacy of a transdermal nanostructured formulation of progesterone (10%) combined with estriol (0.1%) + estradiol (0.25%) for relieving postmenopausal symptoms. METHODS: A total of 66 postmenopausal Brazilian women with climacteric symptoms of natural menopause received transdermal nanostructured formulations of progesterone and estrogens in the forearm daily for 60 months to mimic the normal ovarian secretory pattern. Confocal Raman spectroscopy of hormones in skin layers was performed. Clinical parameters, serum concentrations of estradiol and follicle-stimulating hormone, blood pressure, BI-RADS classification from bilateral mammography, and symptomatic relief were compared between baseline and 60 months post-treatment. Clinicaltrials.gov: NCT02033512. RESULTS: An improvement in climacteric symptoms was reported in 92.5% of women evaluated before and after 60 months of treatment. The serum concentrations of estradiol and follicle-stimulating hormone changed significantly (p<0.05) after treatment; the values of serum follicle-stimulating hormone decreased after 60 months from 82.04±4.9 to 57.12±4.1 IU/mL. A bilateral mammography assessment of the breasts revealed normal results in all women. No adverse health-related events were attributed to this hormone replacement therapy protocol. CONCLUSION: The nanostructured formulation is safe and effective in re-establishing optimal serum levels of estradiol and follicle-stimulating hormone and relieving the symptoms of menopause. This transdermal hormone replacement therapy may alleviate climacteric symptoms in postmenopausal women

Long-term dietary change in Atlantic and Mediterranean Iberia with the introduction of agriculture : a stable isotope perspective

The Neolithic expansion in the Iberian Peninsula is marked by the introduction of livestock and domesticated crops which modified subsistence strategies in an unprecedented manner. Bulk collagen stable carbon and nitrogen isotope analysis has been essential to track these changes, which have largely been discussed in relation to particular geographic areas or single case studies. This paper reviews the available isotope literature to provide a regional, long-term synthesis of dietary changes associated with the expansion of the Neolithic and the establishment of farming economy in the Iberian Peninsula. Bulk collagen stable carbon and nitrogen isotope values of 763 human individuals and 283 faunal remains from the Mesolithic to the Late Neolithic period in Iberia (ca. 8000–3000 cal BC) were collated and analysed using a Bayesian mixing model. The results show that Mesolithic diets were isotopically diverse in both the Atlantic and Mediterranean regions of the Iberian Peninsula, and that a significant decrease in variability happened with the Neolithisation, culminating with the establishment of farming economies and reliance on terrestrial resources in the Late Neolithic