Evaluation of transdermal gels in the delivery of hormone replacement therapy
DOI:
https://doi.org/10.33448/rsd-v10i16.23891Keywords:
Estrogen; Progesterone; Testosterone; Transdermal.Abstract
Hormone replacement therapy (HRT) has been increasingly used in people who have low hormone levels. In menopausal women, the therapy is well known for the association of estrogens and progestin’s, while in hypogonadal men, the therapy is carried out through testosterone replacement. For a safer administration of these hormones, the transdermal route has been used to promote a modified release of the active, in addition to avoiding the first-pass effect of the drugs. However, there is much debate about the effectiveness of transdermal formulations in achieving physiological hormonal serum levels compatible with therapeutic levels. The study aimed to conduct a literature review on the safety and efficacy of transdermal gels in the delivery of sex steroid hormones: estrogen, progesterone, and testosterone, used in HRT. The following platforms were used: Academic Google, PubMed, and Capes Periodicals. The use of the transdermal route for the formulation of gels in the delivery of testosterone achieved efficacy, but safety was not guaranteed by the instability of serum hormone levels in the systemic circulation, while progesterone was not effective, as it was not able to reach ideal physiological levels, while estrogen was well tolerable and effective, being the best alternative compared to oral formulations in efficacy and safer for the patient undergoing HRT.
References
Allen, JR. L. V., Popovich, N.G., & Ansel, H.C. (2007). Formas farmacêuticas e sistemas de liberação de fármacos. (8a ed.), Artmed.
Archer, D. F., Pickar, J. H., MacAllister, D. C., & Warren, M. P. (2012). Transdermal estradiol gel for the treatment of symptomatic postmenopausal women. Menopause, 19(6), 622–629. https://doi.org/10.1097/gme.0b013e31823b8867.
Belkoff, L., Brock, G., Carrara, D., Neijber, A., Ando, M., & Mitchel, J. (2018). Efficacy and safety of testosterone replacement gel for treating hypogonadism in men: Phase III open-label studies. Andrologia, 50(1), 1–7. https://doi.org/10.1111/and.12801.
Brkic, M., Vujovic, S., Ivanisevic, M. F., Ivovic, M., Gajic, M. T., Marina, L., Barac, M., Barac, B., Djogo, A., Malesevic, G., & Franic, D. (2016). The Influence of Progesterone Gel Therapy in the Treatment of Fibrocystic Breast Disease. April, 334–341.
Canonico, M., Carcaillon, L., Plu-Bureau, G., Oger, E., Singh-Manoux, A., Tubert-Bitter, P., Elbaz, A., & Scarabin, P. Y. (2016). Postmenopausal hormone therapy and risk of stroke: Impact of the route of estrogen administration and type of progestogen. Stroke, 47(7), 1734–1741. https://doi.org/10.1161/STROKEAHA.116.013052
Carniél, M. A. (2013). Formulações tópicas magistrais para terapia de reposição hormonal em mulheres no período pós-menopausa e a aplicação da atenção farmacêutica. Trabalho de Conclusão de Curso. Faculdade de farmácia, Universidade Federal do Rio Grande do Sul. https://www.lume.ufrgs.br/handle/10183/144024.
Cauley, J. A. (2015). Estrogen and bone health in men and women. Steroids, 99(Part A), 11–15. https://doi.org/10.1016/j.steroids.2014.12.010.
Cunha, I. V. N. (2020). Uma revisão dos principais sistemas transdérmicos de testosterona utilizados em terapias de reposição hormonal. Trabalho de Conclusão de Curso. Departamento de ciências farmacêuticas, Universidade Federal de Santa Catarina. https://repositorio.ufsc.br/handle/123456789/209575.
Dobs, A. S., Mcgettigan, J., Norwood, P., Howell, J., Waldie, E., & Chen, Y. (2012). A novel testosterone 2% gel for the treatment of hypogonadal males. Journal of Andrology, 33(4), 601–607. https://doi.org/10.2164/jandrol.111.014308.
Du, J. Y., Sanchez, P., Kim, L., Azen, C. G., Zava, D. T., & Stanczyk, F. Z. (2013). Percutaneous progesterone delivery via cream or gel application in postmenopausal women: a randomized cross-over study of progesterone levels in serum, whole blood, saliva, and capillary blood. Menopause (New York, N.Y.), 20(11), 1169–1175. https://doi.org/10.1097/GME.0b013e31828d39a2.
Efros, M., Carrara, D., & Neijber, A. (2016). The efficacy, bioavailability and safety of a novel hydroalcoholic testosterone gel 2% in hypogonadal men: results from phase II open-label studies. Andrologia, 48(6), 637–645. https://doi.org/10.1111/and.12493.
Farwell, W. R., Jette, A. M., Ph, D., Eder, R., Tennstedt, S., Ph, D., Mazer, N. A., Ph, D., Miciek, R., Krasnoff, J., Ph, D., Elmi, A., Knapp, P. E., Brooks, B., Appleman, E., Aggarwal, S., Bhasin, G., Hede-brierley, L., Bhatia, A., & Bhasin, S. (2010). New england journal. 109–122.
Gomes, F. P., & Boldo, M. E. (2020). Investigation of in vitro permeation and release assays of semi-solid topical formulations to standardization of quality requirements on a pharmaceutical industry. Research, Society and Development, 9 (11), e59491110210. https://rsdjournal.org/index.php/rsd/article/view/10210.
Hadgraft, J., & Lane, M. E. (2015). Transdermal delivery of testosterone. European Journal of Pharmaceutics and Biopharmaceutics, 92 (February), 42–48. https://doi.org/10.1016/j.ejpb.2015.02.015.
Johansen, N., Lindén Hirschberg, A., & Moen, M. H. (2020). The role of testosterone in menopausal hormone treatment. What is the evidence? Acta Obstetricia et Gynecologica Scandinavica, 99(8), 966–969. https://doi.org/10.1111/aogs.13819.
Kamal, N. S., Alayoubia, A., Elfakhria, K. H., Ibrahimb, S., Seggel, M., Ashraf, M., Zidan, A. (2020). Effects of formulation variables on the in vitro performance of testosterone transdermal gel. International Journal of Pharmaceutics, 590, 119951 -119965. https://doi.org/10.1016/j.ijpharm.2020.119951
Kaufman, J. M., Miller, M. G., Garwin, J. L., Fitzpatrick, S., Mcwhirter, C., & Brennan, J. J. (2011). Efficacy and Safety Study of 1.62% Testosterone Gel for the Treatment of Hypogonadal Men. Journal of Sexual Medicine, 8(7), 2079–2089. https://doi.org/10.1111/j.1743-6109.2011.02265.x.
Kim, H. J., Oh, Y. K., Lee, J. S., Lee, D.-Y., Choi, D., & Yoon, B.-K. (2014). Effect of Transdermal Estrogen Therapy on Bone Mineral Density in Postmenopausal Korean Women. Journal of Menopausal Medicine, 20(3), 111. https://doi.org/10.6118/jmm.2014.20.3.111.
Kim, H. K., Jeon, S. H., Ryu, K.-J., Kim, T., & Park, H. (2019). Comparison of the Efficacy of Tibolone and Transdermal Estrogen in Treating Menopausal Symptoms in Postmenopausal Women. Journal of Menopausal Medicine, 25(3), 123. https://doi.org/10.6118/jmm.19205
Kumar, A., Banerjee, A., Singh, D., Thakur, G., Kasarpalkar, N., Gavali, S., Gadkar, S., Madan, T., Mahale, S. D., Balasinor, N. H., & Sachdeva, G. (2018). Estradiol : A Steroid with Multiple Facets I Estrogens in Normal Physiology Estrogen synthesis. Hormones Metabolism Research, 50(5), 359–374.
Lima, J. V. de O., Cavalcante, L. C. da S.; Lima, D. C. dos S.; Barbosa, M. C. N. A.; Silva, I. P.; Luz, A. L. R.; Costa, M. H. de A. da; Nunes, M. H.; Batista, M. de K. P.; Júnior, J. L. P.; Cavalcante, G. L. (2020). Risk-benefit of hormone replacement therapy in menopausal women. Research, Society and Development, 9, 5, e07952283. https://rsdjournal.org/index.php/rsd/article/view/2283.
L’Hermite, M. (2017). Bioidentical menopausal hormone therapy: registered hormones (non-oral estradiol ± progesterone) are optimal. Climacteric, 20(4), 331–338. https://doi.org/10.1080/13697137.2017.1291607.
Matsui, R., Ueda, O., Uchida, S., & Namiki, N. (2015). Transdermal absorption of natural progesterone from alcoholic gel formulations with hydrophilic surfactant. Drug Development and Industrial Pharmacy, 41(6), 1026–1029. https://doi.org/10.3109/03639045.2014.925915.
Melo, I. A. C.; Sousa, P. E. L.; Lemos-Jordão, A. J. J. M. Estrogen and progesterone in postmenopausal hormone therapy: a systematic review of influence in cognitive domain. Research, Society and Development, 10 (12), e64101220075, 2021. https://rsdjournal.org/index.php/rsd/article/view/20075.
Mizunuma, H. (2011). Clinical usefulness of a low-dose maintenance therapy with transdermal estradiol gel in Japanese women with estrogen deficiency symptoms. Climacteric, 14(5), 581–589. https://doi.org/10.3109/13697137.2011.570388.
Mohamad, N. (2016). Uma revisão concisa da testosterona e saúde óssea. 1317–1324.
Pardini, D. (2014). Terapia de reposição hormonal na menopausa Hormone replacement therapy in menopause. Arq Bras Endocrinol Metab, 58(2), 10. 172-181. https://doi.org/10.1590/0004-2730000003044.
Piette, P. (2018). The history of natural progesterone, the never-ending story. Climacteric, 21(4), 308–314. https://doi.org/10.1080/13697137.2018.1462792
Polonini, H. C., Brandão, M. A. F., & Raposo, N. R. B. (2011). a Terapia De Reposição Hormonal E a Saúde Da Mulher No Climatério: Riscos E Benefícios. Revista de APS, 14(3), 354–361.
Renoux, C., Dell’aniello, S., & Suissa, S. (2010). Hormone replacement therapy and the risk of venous thromboembolism: A population-based study. Journal of Thrombosis and Haemostasis, 8(5), 979–986. https://doi.org/10.1111/j.1538-7836.2010.03839.x.
Sansone, A., Sansone, M., Selleri, R., Schiavo, A., Gianfrilli, D., Pozza, C., Zitzmann, M., Lenzi, A., & Romanelli, F. (2019). Monitoring testosterone replacement therapy with transdermal gel: when and how? Journal of Endocrinological Investigation, 42(12), 1491–1496. https://doi.org/10.1007/s40618-019-01082-x.
Schulster, M., Bernie, A. M., & Ramasamy, R. (2016). The role of estradiol in male reproductive function. Asian Journal of Andrology, 18(3), 435–440. https://doi.org/10.4103/1008-682X.173932.
Singh, D., Pradhan, M., Nag, M., & Singh, M. R. (2015). Vesicular system: Versatile carrier for transdermal delivery of bioactives. Artificial Cells, Nanomedicine and Biotechnology, 43(4), 282–290. https://doi.org/10.3109/21691401.2014.883401.
Stanczyk, F. Z. (2014). Treatment of postmenopausal women with topical progesterone creams and gels: Are they effective? Climacteric, 17(Suppl 2), 8–11. https://doi.org/10.3109/13697137.2014.944496.
Stute, P., Neulen, J., & Wildt, L. (2016). The impact of micronized progesterone on the endometrium: a systematic review. 7137. https://doi.org/10.1080/13697137.2016.1187123.
Taraborrelli, S. (2015). Physiology, production and action of progesterone. Acta Obstetricia et Gynecologica Scandinavica, 94, 8–16. https://doi.org/10.1111/aogs.12771.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2021 Stephany de Melo Mesquita; Zaida Maria Faria de Freitas; Mariana Sato de Souza Bustamante Monteiro
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
1) Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
2) Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
3) Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.
