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.

The Transdermal Delivery System (BIOLIPID B2®) is a nanoemulsion that can be applied directly to the skin by a metered pump to deliver hormones into the systemic circulation. The aims of this study were to assess the efficacy of BIOLIPID B2® to deliver testosterone systemically and evaluate the short-term effects on Thyroid-Stimulating Hormone (TSH), C-reactive protein (CRP) serum levels and blood pressure in middle aged men with testosterone deficiency. An open label randomized prospective study enrolled 14 Brazilian middle aged men with testosterone deficiency. The volunteers received in the forearm 50mg of transdermal BIOLIPID B2®-testosterone nanostructured formulation daily for 3 months. Confocal Raman Spectroscopy (CRS) was used to determine depth and concentration of testosterone on skin layers. Clinical parameters and serum concentrations were compared between the baseline and 3 months after treatment. Serum concentrations of testosterone, CPR and TSH changed significantly (p<0.05) after treatment. There was, also a significant change in the waist circumference, weight and body mass index (p>0.05) and no changes were observed in the blood pressure. No adverse events were attributed to this transdermal hormone replacement therapy protocol. The BIOLIPID B2® nanoemulsion formulation is safe and effective in reestablishing testosterone and Thyroid-Stimulating Hormone (TSH) serum levels. This transdermal protocol may serve as a strategy for hormone replacement therapy in middle aged men.

OBJECTIVE: The present study aimed to measure in-vivo the depth and the percentage of testosterone in human skin. METHOD: Two healthy young Brazilian volunteers were evaluated through a Confocal Raman Spectroscopy probe on the right volar forearm. Testosterone spectroscopy of was performed on the Stratum Corneum, Viable Epidermis and Dermis; the percentage concentration of testosterone was compared between the baseline and one hour after local application of a transdermal nanostructured testosterone (5%) formulation. RESULTS: To the best of our knowledge, this is the first time that the depth and percentage of testosterone has been evaluated non-invasively in-vivo. No adverse events were attributed to this protocol. The method is effective in differentially measuring testosterone in the skin layers. CONCLUSION: This protocol may serve as a good choice for rapid hormone quantification for forensic or medical purposes.