Benefits and risks of testosterone pellets in women: A systematic review of the literature
Cover of our Vol. 11, Issue 2, 2024
PDF (Español (España))

Keywords

Androgens
Testosterone
Drug Implants
Efficacy
Health Risk
Safety
Women

How to Cite

Espitia de la Hoz, F. . (2024). Benefits and risks of testosterone pellets in women: A systematic review of the literature. Revista Colombiana De Endocrinología, Diabetes &Amp; Metabolismo, 11(2). https://doi.org/10.53853/encr.11.2.802

Abstract

Background: testosterone implants can increase serum testosterone levels.

Purpose: to evaluate the benefits and risks of testosterone implants in women, through a systematic review of the literature.

Methodology: a systematic review of the literature was carried out about the benefits and risks of the use of testosterone implants in women. The search was carried out in different electronic databases (Medline, Central, Embase, among others), with free and standardized search terms. In the benefits, the reactivation of sexual desire was considered as the primary outcome; and in the risks the proportion of acne, spotting, clitoromegaly and hirsutism.

Results: seventy-nine publications were included. We found no randomized controlled trials evaluating the benefits and risks of testosterone implants in women. In few retrospective observational publications, the use of testosterone implants in women was associated with improvement in several domains of sexual function and personal distress. Data on long-term efficacy and safety are scarce and the quality of evidence is low. Common risks and adverse effects were found: acne, alopecia and hirsutism, as well as erythrocytosis (polycythemia), extrusion, cellulitis/infection and hematomas.

Conclusions: The benefits of testosterone implants in women are outweighed by the risks, and the incidence of irreversible adverse effects may be much higher than has been reported. Close monitoring of the rational use of testosterone implants in women is necessary.

https://doi.org/10.53853/encr.11.2.802
PDF (Español (España))

References

Lobo RA. Androgens in postmenopausal women: production, possible role, and replacement options. Obstet Gynecol Surv. 2001 jun.;56(6):361-76. https://doi.org/10.1097/00006254-200106000-00022

Simpson ER, Davis SR. Minireview: aromatase and the regulation of estrogen biosynthesis--some new perspectives. Endocrinology. 2001 nov.;142(11):4589-94. https://doi.org/10.1210/en.142.11.4589

Labrie F, Luu-The V, Lin SX, Simard J, Labrie C, El-Alfy M, et al. Intracrinology: role of the family of 17 beta-hydroxysteroid dehydrogenases in human physiology and disease. J Mol Endocrinol. 2000 ag.;25(1):1-16. https://doi.org/10.1677/jme.0.0250001

Subramanian A, Salhab M, Mokbel K. Oestrogen producing enzymes and mammary carcinogenesis: a review. Breast Cancer Res Treat. 2008 sept.;111(2):191-202. https://doi.org/10.1007/s10549-007-9788-0

Davison SL, Bell R, Donath S, Montalto JG, Davis SR. Androgen levels in adult females: changes with age, menopause, and oophorectomy. J Clin Endocrinol Metab. 2005 jul.;90(7):3847-53. https://doi.org/10.1210/jc.2005-0212

Espitia De La Hoz FJ. Eficacia y seguridad de la testosterona en el tratamiento del deseo sexual hipoactivo en mujeres: ¿qué dice la evidencia? Rev Int Androl. 2023;21(1):100328. https://doi.org/10.1016/j.androl.2021.09.002

Baillargeon J, Urban RJ, Ottenbacher KJ, Pierson KS, Goodwin JS. Trends in androgen prescribing in the United States, 2001 to 2011. JAMA Intern Med. 2013 ag. 12;173(15):1465-6. https://doi.org/10.1001/jamainternmed.2013.6895. Fe de errata en: JAMA Intern Med. 2013 ag. 12;173(15):1477.

Irwig MS, Fleseriu M, Jonklaas J, Tritos NA, Yuen KCJ, Correa R, et al. Off-label use and misuse of testosterone, growth hormone, thyroid hormone, and adrenal supplements: risks and costs of a growing problem. Endocr Pract. 2020 mzo.;26(3):340-53. https://doi.org/10.4158/PS-2019-0540

Glaser R, York AE, Dimitrakakis C. Beneficial effects of testosterone therapy in women measured by the validated Menopause Rating Scale (MRS). Maturitas. 2011 abr.;68(4):355-61. https://doi.org/10.1016/j.maturitas.2010.12.001

Greenblatt RB, Suran RR. Indications for hormonal pellets in the therapy of endocrine and gynecic disorders. Am J Obstet Gynecol. 1949 febr.;57(2):294-301. https://doi.org/10.1016/0002-9378(49)90429-9

Donovitz GS. Low complication rates of testosterone and estradiol implants for androgen and estrogen replacement therapy in over 1 million procedures. Ther Adv Endocrinol Metab. 2021 my. 27;12:20420188211015238. https://doi.org/10.1177/20420188211015238

Glaser RL, Dimitrakakis C. Reduced breast cancer incidence in women treated with subcutaneous testosterone, or testosterone with anastrozole: a prospective, observational study. Maturitas. 2013 dic.;76(4):342-9. https://doi.org/10.1016/j.maturitas.2013.08.002

Donovitz G, Cotten M. Breast cancer incidence reduction in women treated with subcutaneous testosterone: Testosterone Therapy and Breast Cancer Incidence Study. Eur J Breast Health. 2021 mzo. 31;17(2):150-6. https://doi.org/10.4274/ejbh.galenos.2021.6213

Glaser RL, York AE, Dimitrakakis C. Incidence of invasive breast cancer in women treated with testosterone implants: a prospective 10-year cohort study. BMC Cancer. 2019 dic. 30;19(1):1271. https://doi.org/10.1186/s12885-019-6457-8

Parish SJ, Simon JA, Davis SR, Giraldi A, Goldstein I, Goldstein SW, et al. International society for the study of women's sexual health clinical practice guideline for the use of systemic testosterone for hypoactive sexual desire disorder in women. J Sex Med. 2021 my.;18(5):849-67. https://doi.org/10.1016/j.jsxm.2020.10.009

Davis SR, Baber R, Panay N, Bitzer J, Perez SC, Islam RM, et al. Global consensus position statement on the use of testosterone therapy for women. J Clin Endocrinol Metab. 2019 oct. 1;104(10):4660-6. https://doi.org/10.1210/jc.2019-01603

Riva JJ, Malik KM, Burnie SJ, Endicott AR, Busse JW. What is your research question? An introduction to the PICOT format for clinicians. J Can Chiropr Assoc. 2012 sept.;56(3):167-71.

Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane collaboration's tool for assessing risk of bias in randomised trials. BMJ. 2011 oct. 18;343:d5928. https://doi.org/10.1136/bmj.d5928

Schuneman H, Brozek J, Guyatt G, Oxman A. GRADE Handbook [internet]. 2013 (citado 2022 oct. 21). https://gdt.gradepro.org/app/handbook/handbook.html

Ministerio de Salud. Resolución 8430 de 1993. https://www.minsalud.gov.co/sites/rid/Lists/BibliotecaDigital/RIDE/DE/DIJ/RESOLUCION-8430-DE-1993.pdf

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021 mzo. 29;372:n71. https://doi.org/10.1136/bmj.n71

Bancroft J. Sexual effects of androgens in women: some theoretical considerations. Fertil Steril. 2002 abr.;77(supl. 4):S55-9. https://doi.org/10.1016/S0015-0282(02)02961-8

Davis SR, Davison SL, Donath S, Bell RJ. Circulating androgen levels and self-reported sexual function in women. JAMA. 2005 jul. 6;294(1):91-6. https://doi.org/10.1001/jama.294.1.91

Davis SR, Braunstein GD. Efficacy and safety of testosterone in the management of hypoactive sexual desire disorder in postmenopausal women. J Sex Med. 2012 abr.;9(4):1134-48. https://doi.org/10.1111/j.1743-6109.2011.02634.x

Islam RM, Bell RJ, Green S, Page MJ, Davis SR. Safety and efficacy of testosterone for women: a systematic review and meta-analysis of randomised controlled trial data. Lancet Diabetes Endocrinol. 2019 oct.;7(10):754-66. https://doi.org/10.1016/S2213-8587(19)30189-5

Somboonporn W, Davis S, Seif MW, Bell R. Testosterone for peri- and postmenopausal women. Cochrane Database Syst Rev. 2005 oct. 19;(4):CD004509. https://doi.org/10.1002/14651858.CD004509.pub2

Snabes MC, Simes SM. Approved hormonal treatments for HSDD: an unmet medical need. J Sex Med. 2009 jul.;6(7):1846-9. https://doi.org/10.1111/j.1743-6109.2009.01294.x

Krapf JM, Simon JA. A sex-specific dose-response curve for testosterone: could excessive testosterone limit sexual interaction in women? Menopause. 2017 abr.;24(4):462-70. https://doi.org/10.1097/GME.0000000000000863

Donovitz GS. A personal prospective on testosterone therapy in women-what we know in 2022. J Pers Med. 2022 jul. 22;12(8):1194. https://doi.org/10.3390/jpm12081194

Grober ED, Garbens A, Božovi? A, Kulasingam V, Fanipour M, Diamandis EP. Accuracy of testosterone concentrations in compounded testosterone products. J Sex Med. 2015 jun.;12(6):1381-8. https://doi.org/10.1111/jsm.12898

Chen W, Thiboutot D, Zouboulis CC. Cutaneous androgen metabolism: basic research and clinical perspectives. J Invest Dermatol. 2002 nov.;119(5):992-1007. https://doi.org/10.1046/j.1523-1747.2002.00613.x

Kircik LH. Androgens and acne: perspectives on clascoterone, the first topical androgen receptor antagonist. Expert Opin Pharmacother. 2021 sept.;22(13):1801-6. https://doi.org/10.1080/14656566.2021.1918100

Elraiyah T, Sonbol MB, Wang Z, Khairalseed T, Asi N, Undavalli C, et al. Clinical review: The benefits and harms of systemic testosterone therapy in postmenopausal women with normal adrenal function: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2014 oct.;99(10):3543-50. https://doi.org/10.1210/jc.2014-2262

Mesbah F, Bordbar H, Talaei Khozani T, Dehghani F, Mirkhani H. The non-preventive effects of human menopausal gonadotropins on ovarian tissues in Nandrolone decanoate-treated female rats: A histochemical and ultra-structural study. Int J Reprod Biomed. 2018 mzo.;16(3):159-74. https://doi.org/10.29252/ijrm.16.3.159

Andrade GHB, Simão VA, Souza BR, Chuffa LGA, Camargo ICC. Sex steroid receptors profiling is influenced by nandrolone decanoate in the ampulla of the fallopian tube: Post-treatment and post-recovery analyses. Tissue Cell. 2018 febr.;50:79-88. https://doi.org/10.1016/j.tice.2018.01.001

de Almeida Chuffa LG, de Souza RB, Frei F, de Fátima Paccola Mesquita S, Camargo IC. Nandrolone decanoate and physical effort: histological and morphometrical assessment in adult rat uterus. Anat Rec (Hoboken). 2011 febr.;294(2):335-41. https://doi.org/10.1002/ar.21314

Ferriman D, Gallwey JD. Clinical assessment of body hair growth in women. J Clin Endocrinol Metab. 1961 nov.;21:1440-7. https://doi.org/10.1210/jcem-21-11-1440

Barth JH, Catalan J, Cherry CA, Day A. Psychological morbidity in women referred for treatment of hirsutism. J Psychosom Res. 1993 sept.;37(6):615-9. https://doi.org/10.1016/0022-3999(93)90056-L

Rosenfield RL. Clinical practice. Hirsutism. N Engl J Med. 2005 dic. 15;353(24):2578-88. https://doi.org/10.1056/NEJMcp033496

Hawryluk EB, English III JC. Female adolescent hair disorders. J Pediatr Adolesc Gynecol. 2009 ag.;22(4):271-81. https://doi.org/10.1016/j.jpag.2009.03.007

Azziz R, Carmina E, Sawaya ME. Idiopathic hirsutism. Endocr Rev. 2000 ag.;21(4):347-62. https://doi.org/10.1210/edrv.21.4.0401

Mihailidis J, Dermesropian R, Taxel P, Luthra P, Grant-Kels JM. Endocrine evaluation of hirsutism. Int J Womens Dermatol. 2015 jun. 4;1(2):90-4. https://doi.org/10.1016/j.ijwd.2015.04.003

Taheri S, Zararsiz G, Karaburgu S, Borlu M, Ozgun MT, Karaca Z, et al. Is idiopathic hirsutism (IH) really idiopathic? mRNA expressions of skin steroidogenic enzymes in women with IH. Eur J Endocrinol. 2015 oct.;173(4):447-54. https://doi.org/10.1530/EJE-15-0460

Unluhizarci K, Hacioglu A, Taheri S, Karaca Z, Kelestimur F. Idiopathic hirsutism: Is it really idiopathic or is it misnomer? World J Clin Cases. 2023 Jan 16;11(2):292-298. https://doi.org/10.12998/wjcc.v11.i2.292

Maroulis GB. Evaluation of hirsutism and hyperandrogenemia. Fertil Steril. 1981 Sep;36(3):273-305. https://doi.org/10.1016/S0015-0282(16)45728-6

Grimstad F, Boskey ER, Taghinia A, Estrada CR, Ganor O. The role of androgens in clitorophallus development and possible applications to transgender patients. Andrology. 2021 Nov;9(6):1719-1728. https://doi.org/10.1111/andr.13016

Fernández-Balsells MM, Murad MH, Lane M, Lampropulos JF, Albuquerque F, Mullan RJ, et al. Clinical review 1: Adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2010 jun.;95(6):2560-75. https://doi.org/10.1210/jc.2009-2575

Wierman ME, Arlt W, Basson R, Davis SR, Miller KK, Murad MH, et al. Androgen therapy in women: a reappraisal: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2014 oct.;99(10):3489-510. https://doi.org/10.1210/jc.2014-2260

Espitia De La Hoz FJ. Sexo ilimitado / El vuelo hacia una sexualidad más placentera. Bogotá D.C.: Editorial Bolívar; 2015.

Dunsmoor-Su R, Fuller A, Voedisch A. Testosterone therapy in women: a clinical challenge. Obstet Gynecol. 2021 nov. 1;138(5):809-12. https://doi.org/10.1097/AOG.0000000000004566

Simon JA, Kapner MD. The saga of testosterone for menopausal women at the Food and Drug Administration (FDA). J Sex Med. 2020 abr.;17(4):826-9. https://doi.org/10.1016/j.jsxm.2020.01.009

Kanakis GA, Tsametis CP, Goulis DG. Measuring testosterone in women and men. Maturitas. 2019 jul.;125:41-4. https://doi.org/10.1016/j.maturitas.2019.04.203

Kelm RC, Adotama P, Stratton JS, Levin JI. Testosterone pellet-induced generalized drug eruption. Cutis. 2020 dic.;106(6):E15-6. https://doi.org/10.12788/cutis.0158

Heldt Manica LA, Cohen PR. Testosterone pellet associated dermatitis: report and review of testopel-related cutaneous adverse effects. Cureus. 2017 ag. 11;9(8):e1560. doi: 10.7759/cureus.1560.

Bachmann G, Bancroft J, Braunstein G, Burger H, Davis S, Dennerstein L, et al. Female androgen insufficiency: the Princeton consensus statement on definition, classification, and assessment. Fertil Steril. 2002 abr.;77(4):660-5. https://doi.org/10.1016/S0015-0282(02)02969-2

Jang C, Boyle JA, Vincent A. Global consensus statement on testosterone therapy for women: an Australian perspective. Med J Aust. 2020 nov.;213(10):449-52.e1. https://doi.org/10.5694/mja2.50837

Dennis C. Brain development: the most important sexual organ. Nature. 2004 en. 29;427(6973):390-2. https://doi.org/10.1038/427390a

Pettigrew JA, Novick AM. Hypoactive sexual desire disorder in women: physiology, assessment, diagnosis, and treatment. J Midwifery Women Health. 2021 nov.;66(6):740-8. https://doi.org/10.1111/jmwh.13283

Achilli C, Pundir J, Ramanathan P, Sabatini L, Hamoda H, Panay N. Efficacy and safety of transdermal testosterone in postmenopausal women with hypoactive sexual desire disorder: a systematic review and meta-analysis. Fertil Steril. 2017 febr.;107(2):475-82.e15. https://doi.org/10.1016/j.fertnstert.2016.10.028

Espitia De La Hoz FJ. Terapia de reemplazo hormonal combinada con testosterona para el tratamiento del trastorno del deseo sexual hipoactivo en mujeres en climaterio. Arch Med (Manizales). 2020;20(1):71-85. https://doi.org/10.30554/archmed.20.1.3388.2020

Espitia de la Hoz FJ, Marega O, Orozco Gallego H. Manejo farmacológico de la disfunción sexual femenina en la postmenopausia, con tibolona y testosterona. Rev Sexología. 2016;5(2):9-18.

Donovitz G, Schwartz E, Miller C, Barber M, Comite F, Janson K, et al. Testosterone insufficiency and treatment in women: international expert consensus. MSP Medicina Salud Publica. https://medicinaysaludpublica.com/testosterone-insufficiency-and-treatment-in-women-international-expert-consensus/

Bhasin S, Basaria S. Diagnosis and treatment of hypogonadism in men. Best Pract Res Clin Endocrinol Metab. 2011 abr.;25(2):251-70. https://doi.org/10.1016/j.beem.2010.12.002

Jick SS, Hagberg KW. The risk of adverse outcomes in association with use of testosterone products: a cohort study using the UK-based general practice research database. Br J Clin Pharmacol. 2013 en.;75(1):260-70. https://doi.org/10.1111/j.1365-2125.2012.04326.x

Davis SR. What is the position of testosterone in the care of women? Climacteric. 2019 oct.;22(5):427-8. https://doi.org/10.1080/13697137.2019.1635581

Traish AM, Feeley RJ, Guay AT. Testosterone therapy in women with gynecological and sexual disorders: a triumph of clinical endocrinology from 1938 to 2008. J Sex Med. 2009 febr.;6(2):334-51. https://doi.org/10.1111/j.1743-6109.2008.01121.x

Bancroft J. The endocrinology of sexual arousal. J Endocrinol. 2005 sept.;186(3):411-27. https://doi.org/10.1677/joe.1.06233

Reis SL, Abdo CH. Benefits and risks of testosterone treatment for hypoactive sexual desire disorder in women: a critical review of studies published in the decades preceding and succeeding the advent of phosphodiesterase type 5 inhibitors. Clinics (Sao Paulo). 2014;69(4):294-303. https://doi.org/10.6061/clinics/2014(04)11

Schwenkhagen A, Studd J. Role of testosterone in the treatment of hypoactive sexual desire disorder. Maturitas. 2009 jun. 20;63(2):152-9. https://doi.org/10.1016/j.maturitas.2009.02.011

Aub JC. The use of testosterone. N Engl J Med 1940;222:877-81. https://doi.org/10.1056/NEJM194005232222104

Greenblatt RB. Testosterone propionate pellet implantation in genecic disorders. JAMA. 1943;121(1):17-24. https://doi.org/10.1001/jama.1943.02840010019004

Salinger SL, Weber AA, Borth R. Proliferative effect of testosterone propionate on human vaginal epithelium. Acta Endocrinol (Copenh). 1950;4(3):265-84. https://doi.org/10.1530/acta.0.0040265

Morgentaler A, Traish A. The History of Testosterone and the Evolution of its Therapeutic Potential. Sex Med Rev. 2020 abr.;8(2):286-96. https://doi.org/10.1016/j.sxmr.2018.03.002

Espitia De La Hoz FJ. El sexo: arte y placer. Bogotá D.C.: Editorial Bolívar; 2020.

Uloko M, Rahman F, Puri LI, Rubin RS. The clinical management of testosterone replacement therapy in postmenopausal women with hypoactive sexual desire disorder: a review. Int J Impot Res. 2022 oct. 5. https://doi.org/10.1038/s41443-022-00613-0

Schover LR. Androgen therapy for loss of desire in women: is the benefit worth the breast cancer risk? Fertil Steril. 2008 jul.;90(1):129-40. https://doi.org/10.1016/j.fertnstert.2007.05.057

Martínez-García A, Davis SR. Testosterone use in postmenopausal women. Climacteric. 2021 febr.;24(1):46-50. https://doi.org/10.1080/13697137.2020.1796961

Acuña-San Martín MA., Gallardo-González RP. Implante de testosterona para la mujer, evaluación de seguridad y efectividad en esta vía de administración. Rev Chil Obstet Ginecol. 2021; 86(6):516-20. https://doi.org/10.24875/RECHOG.M21000039

Gouveia M, Sanches R, Andrade S, Carmona S, Ferreira C. O Papel da Testosterona na Melhoria do Desejo Sexual da Mulher Pós-Menopáusica: Uma Revisão Baseada na Evidência [The Role of Testosterone in The Improvement of Sexual Desire in Postmenopausal Women: An Evidence-Based Clinical Review]. Acta Med Port. 2018 nov. 30;31(11):680-90. Portuguese. https://doi.org/10.20344/amp.9277

Ministerio de Salud y Protección Social. Alerta sanitaria: dirección de medicamentos y productos biológicos. Invima. https://app.invima.gov.co/alertas/ckfinder/userfiles/files/ALERTAS%20SANITARIAS/medicamentos_pbiologicos/2023/Mayo/Alerta%20sanitaria_150-2023_REJUVCHIP%C2%AE%20-%20PELLETS%20DE%20TESTOSTERONA.pdf

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Copyright (c) 2024 Revista Colombiana de Endocrinología, Diabetes & Metabolismo

Dimensions


PlumX


Downloads

Download data is not yet available.