This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Javanbakht, M. Articles by Bhasin, S. Search for Related Content PubMed PubMed Citation Articles by Javanbakht, M. Articles by Bhasin, S.

Pharmacokinetics of a Novel Testosterone Matrix Transdermal System in Healthy, Premenopausal Women and Women Infected with the Human Immunodeficiency Virus¹

Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, California 90059; Harbor-University of California-Los Angeles Medical Center, Torrance, California 90509; and Watson Laboratories, Inc.-Utah, Salt Lake City, Utah 84108

Address all correspondence and requests for reprints to: Shalender Bhasin, M.D., University of California School of Medicine, Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, 1731 East 120th Street, Los Angeles, California 90059.

The clinical consequences of androgen deficiency in human immunodeficiency virus (HIV)-infected women remain underappreciated. The pharmacokinetics of transdermally administered testosterone in premenopausal women and HIV-infected women have not been studied. In this study we compared the pharmacokinetics of a novel testosterone matrix transdermal system (TMTDS) in healthy premenopausal women and women infected with HIV. Eight menstruating HIV-infected women, 18–50 yr of age, who had been receiving stable antiretroviral therapy, including a protease inhibitor, for at least 12 weeks and nine healthy, menstruating women of comparable age were enrolled. After baseline sampling during a 24-h control period in the early follicular phase (days 1–6), two TMTDS patches were applied with an expected delivery rate of 300 µg testosterone daily over an application period of 3–4 days. After 72 h, the patches were removed, a second set of two patches was applied, and blood samples were drawn over 96 h.

Baseline serum total and free testosterone levels were lower in HIV-infected women than in healthy women. A diurnal rhythm of testosterone secretion, with higher levels in the morning and lower levels in the late afternoon, was apparent in both groups of women. Free testosterone levels were in the midnormal range at baseline in healthy women and increased above the upper limit of normal during TMTDS application. In HIV-infected women, free testosterone levels were in the low normal range at baseline and rose into the upper normal range during patch application. Serum total testosterone levels increased into the midnormal range in HIV-infected women and into the upper normal range in healthy women during patch application. The mean increments in free and total testosterone levels were significantly lower in HIV-infected women than in healthy women. Testosterone bioavailability, expressed as the mean ± SEM baseline-subtracted area under the total testosterone curve, was significantly greater in healthy women than in HIV-infected women [3323 ± 566 ng/dL·h (115 ± 20 nmol/L·h) vs. 1506 ± 316 ng/dL·h (52 ± 11 nmol/L·h); P = 0.016]. Assuming a daily testosterone delivery rate of 300 µg/day, the apparent plasma clearance was significantly higher in HIV-infected women than in healthy women (2531 ± 469 vs. 1127 ± 217 L/dayl P = 0.022), respectively. There was no significant change from baseline in serum LH, sex hormone-binding globulin, and estradiol levels in either group. Serum FSH levels showed a greater decrease from baseline in healthy women.

A regimen of two testosterone patches applied twice a week can maintain serum total and free testosterone levels in the mid- to upper normal range, respectively, in HIV-infected women with low testosterone levels. During TMTDS application, the increments in serum total and free testosterone levels are lower in HIV-infected women than in healthy women, presumably due to increased plasma clearance or decreased absorption. Further studies are needed to assess the effects of physiological androgen replacement in HIV-infected women.

This article has been cited by other articles:

				S. Bhasin, R. A. Parker, F. Sattler, R. Haubrich, B. Alston, T. Umbleja, C. M. Shikuma, and for the AIDS Clinical Trials Group Protocol A5079 Effects of Testosterone Supplementation on Whole Body and Regional Fat Mass and Distribution in Human Immunodeficiency Virus-Infected Men with Abdominal Obesity J. Clin. Endocrinol. Metab., March 1, 2007; 92(3): 1049 - 1057. [Abstract] [Full Text] [PDF]

				A. R. Cappola, S. J. Ratcliffe, S. Bhasin, M. R. Blackman, J. Cauley, J. Robbins, J. M. Zmuda, T. Harris, and L. P. Fried Determinants of Serum Total and Free Testosterone Levels in Women over the Age of 65 Years J. Clin. Endocrinol. Metab., February 1, 2007; 92(2): 509 - 516. [Abstract] [Full Text] [PDF]

				M. E. Wierman, R. Basson, S. R. Davis, S. Khosla, K. K. Miller, W. Rosner, and N. Santoro Androgen Therapy in Women: An Endocrine Society Clinical Practice Guideline J. Clin. Endocrinol. Metab., October 1, 2006; 91(10): 3697 - 3710. [Abstract] [Full Text] [PDF]

				A. B. Singh, M. L. Lee, I. Sinha-Hikim, M. Kushnir, W. Meikle, A. Rockwood, S. Afework, and S. Bhasin Pharmacokinetics of a Testosterone Gel in Healthy Postmenopausal Women J. Clin. Endocrinol. Metab., January 1, 2006; 91(1): 136 - 144. [Abstract] [Full Text] [PDF]

				S. N. Kalantaridou, K. A. Calis, N. A. Mazer, H. Godoy, and L. M. Nelson A Pilot Study of an Investigational Testosterone Transdermal Patch System in Young Women with Spontaneous Premature Ovarian Failure J. Clin. Endocrinol. Metab., December 1, 2005; 90(12): 6549 - 6552. [Abstract] [Full Text] [PDF]

				H. H. Choi, P. B. Gray, T. W. Storer, O. M. Calof, L. Woodhouse, A. B. Singh, C. Padero, R. P. Mac, I. Sinha-Hikim, R. Shen, et al. Effects of Testosterone Replacement in Human Immunodeficiency Virus-Infected Women with Weight Loss J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1531 - 1541. [Abstract] [Full Text] [PDF]

				S. Davison, J. Thipphawong, J. Blanchard, K. Liu, R. Morishige, I. Gonda, J. Okikawa, J. Adams, A. Evans, B. Otulana, et al. Pharmacokinetics and Acute Safety of Inhaled Testosterone in Postmenopausal Women J. Clin. Pharmacol., February 1, 2005; 45(2): 177 - 184. [Abstract] [Full Text] [PDF]

				S. Grinspoon, C. Corcoran, T. Stanley, J. Rabe, and S. Wilkie Mechanisms of Androgen Deficiency in Human Immunodeficiency Virus-Infected Women with the Wasting Syndrome J. Clin. Endocrinol. Metab., September 1, 2001; 86(9): 4120 - 4126. [Abstract] [Full Text] [PDF]

				J. C. Lo and M. Schambelan Reproductive Function in Human Immunodeficiency Virus Infection J. Clin. Endocrinol. Metab., June 1, 2001; 86(6): 2338 - 2343. [Full Text] [PDF]