Decreased androgen levels and improved menstrual pattern after angiotensin II receptor antagonist telmisartan treatment in four hypertensive patients with polycystic ovary syndrome: case series

Mojca Jensterle, Andrej Janez, Bojan Vrtovec, Helena Meden-Vrtovec, Marija Pfeifer, Janez Prezelj, Tomaz Kocjan, Mojca Jensterle, Andrej Janez, Bojan Vrtovec, Helena Meden-Vrtovec, Marija Pfeifer, Janez Prezelj, Tomaz Kocjan

Abstract

We describe 4 consecutive hypertensive women with polycystic ovary syndrome, classified according to the National Institute of Child Health and Human Development (NICHD) criteria, treated with telmisartan 40 mg/d for six months. Blood pressure, menstrual pattern, body mass index (BMI), homeostasis model assessment of insulin resistance, testosterone, dehydroepiandrosterone sulfate (DHEAS), and androstenedione were recorded and measured before and after telmisartan treatment. Obese hypertensive polycystic ovary syndrome patients had a decrease in systolic blood pressure. Marked drop-off in serum androgen concentrations was observed in all four patients. Three patients improved their menstrual cyclicity. The improvements were independent of changes in weight. The reduction of androgen concentrations and improvement in menstrual pattern was achieved despite a non-significant change of fasting insulin levels in patients, who were not considered severely insulin resistant at baseline. These findings may provide a new basis for a proper choice of the antihypertensive drug in hypertensive women with polycystic ovary syndrome.

References

    1. Glueck CJ, Papanna R, Wang P, Goldenberg N, Sieve-Smith L. Incidence and treatment of metabolic syndrome in newly referred women with confirmed polycystic ovarian syndrome. Metabolism. 2003;52:908–15. doi: 10.1016/S0026-0495(03)00104-5.
    1. Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev. 1997;18:774–800. doi: 10.1210/er.18.6.774.
    1. Ehrmann DA, Liljenquist DR, Kasza K, Azziz R, Legro RS, Ghazzi MN. Prevalence and predictors of the metabolic syndrome in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2006;91:48–53. doi: 10.1210/jc.2005-1329.
    1. Legro RS, Kunselman AR, Dodson WC, Dunaif A. Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women. J Clin Endocrinol Metab. 1999;84:165–9. doi: 10.1210/jc.84.1.165.
    1. Legro RS, Kunselman AR, Dunaif A. Prevalence and predictors of dyslipidemia in women with polycystic ovary syndrome. Am J Med. 2001;111:607–13. doi: 10.1016/S0002-9343(01)00948-2.
    1. Guzick DS, Talbott EO, Sutton-Tyrrell K, Herzog HC, Kuller LH, Wolfson SK., Jr Carotid atherosclerosis in women with polycystic ovary syndrome: initial results from a case-control study. Am J Obstet Gynecol. 1996;174:1224–9. doi: 10.1016/S0002-9378(96)70665-8.
    1. Harborne L, Fleming R, Lyall H, Norman J, Sattar N. Descriptive review of the evidence for the use of metformin in polycystic ovary syndrome. Lancet. 2003;361:1894–901. doi: 10.1016/S0140-6736(03)13493-9.
    1. Lord JM, Flight IH, Norman RJ. Metformin in polycystic ovary syndrome: systematic review and meta-analysis. BMJ. 2003;327:951–3. doi: 10.1136/bmj.327.7421.951.
    1. Costello MF, Eden JA. A systematic review of the reproductive system effects of metformin in patients with polycystic ovary syndrome. Fertil Steril. 2003;79:1–3. doi: 10.1016/S0015-0282(02)04554-5.
    1. Azziz R, Ehrmann D, Legro RS, Whitcomb RW, Hanley R, Fereshetian AG, et al. Troglitazone improves ovulation and hirsutism in the polycystic ovary syndrome: a multicenter, double blind, placebo-controlled trial. J Clin Endocrinol Metab. 2001;86:1626–32. doi: 10.1210/jc.86.4.1626.
    1. Sepilian V, Nagamani M. Effects of rosiglitazone in obese women with polycystic ovary syndrome and severe insulin resistance. J Clin Endocrinol Metab. 2005;90:60–5. doi: 10.1210/jc.2004-1376.
    1. Ghazeeri G, Kutteh WH, Bryer-Ash M, Haas D, Ke RW. Effect of rosiglitazone on spontaneous and clomiphene citrate-induced ovulation in women with polycystic ovary syndrome. Fertil Steril. 2003;79:562–6. doi: 10.1016/S0015-0282(02)04843-4.
    1. Cataldo NA, Abbasi F, McLaughlin TL, Basina M, Fechner PY, Giudice LC, et al. Metabolic and ovarian effects of rosiglitazone treatment for 12 weeks in insulin-resistant women with polycystic ovary syndrome. Hum Reprod. 2006;21:109–20. doi: 10.1093/humrep/dei289.
    1. Benson SC, Pershadsingh HA, Ho CI, Chittiboyina A, Desai P, Pravenec M, et al. Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPARgamma-modulating activity. Hypertension. 2004;43:993–1002. doi: 10.1161/01.HYP.0000123072.34629.57.
    1. Pershadsingh HA, Kurtz TW. Insulin-sensitizing effects of telmisartan: implications for treating insulin-resistant hypertension and cardiovascular disease. Diabetes Care. 2004;27:1015. doi: 10.2337/diacare.27.4.1015.
    1. Kurtz TW, Pravenec M. Antidiabetic mechanisms of angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists: beyond the renin-angiotensin system. J Hypertens. 2004;22:2253–61. doi: 10.1097/00004872-200412000-00003.
    1. Kurtz TW. Treating the metabolic syndrome: telmisartan as a peroxisome proliferator-activated receptor-gamma activator. Acta Diabetol. 2005;42(Suppl 1):S9–16. doi: 10.1007/s00592-005-0176-0.
    1. Kurtz TW. New treatment strategies for patients with hypertension and insulin resistance. Am J Med. 2006;119(5) Suppl 1:S24–30. doi: 10.1016/j.amjmed.2006.01.011.
    1. Zawadzki JK, Dunaif A. Diagnostic criteria for polycystic ovary syndrome: towards a rational approach. In: Dunaif A, Givens JR, Haseltine F, Merriam GR, editors. Polycystic ovary syndrome. Boston (MA): Blackwell 1992. p. 377-84.
    1. Chobanian AV, Bakris GL, Black HR, Cushman WC. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289:2560–70. doi: 10.1001/jama.289.19.2560.
    1. Moncada E. Familial study of hirsutism. J Clin Endocrinol Metab. 1970;31:556–64.
    1. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–9. doi: 10.1007/BF00280883.
    1. Rautio K, Tapanainen JS, Ruokonen A, Morin-Papunen LC. Endocrine and metabolic effects of rosiglitazone in overweight women with PCOS: a randomized placebo-controlled study. Hum Reprod. 2006;21:1400–7. doi: 10.1093/humrep/dei505.
    1. Dereli D, Dereli T, Bayraktar F, Ozgen AG, Yilmaz C. Endocrine and metabolic effects of rosiglitazone in non-obese women with polycystic ovary disease. Endocr J. 2005;52:299–308. doi: 10.1507/endocrj.52.299.
    1. Kumari AS, Haq A, Jayasundaram R, Abdel-Wareth LO, Al Haija SA, Alvares M. Metformin monotherapy in lean women with polycystic ovary syndrome. Reprod Biomed Online. 2005;10:100–4.
    1. Yilmaz M, Biri A, Karakoc A, Toruner F, Bingol B, Cakir N, et al. The effects of rosiglitazone and metformin on insulin resistance and serum androgen levels in obese and lean patients with polycystic ovary syndrome. J Endocrinol Invest. 2005;28:1003–8.
    1. Mitwally MF, Witchel SF, Casper RF. Troglitazone: a possible modulator of ovarian steroidogenesis. J Soc Gynecol Investig. 2002;9:163–7. doi: 10.1016/S1071-5576(02)00149-1.
    1. Furnsinn C, Nowotny P, Brunmair B, Gras F, Roden M, Waldhausl W, et al. Thiazolidinediones influence plasma steroids of male obese Zucker rats. Endocrinology. 2002;143:327. doi: 10.1210/en.143.1.327.
    1. Vierhapper H, Nowotny P, Waldhausl W. Reduced production rates of testosterone and dihydrotestosterone in healthy men treated with rosiglitazone. Metabolism. 2003;52:230–2. doi: 10.1053/meta.2003.50028.
    1. Gasic S, Bodenburg Y, Nagamani M, Green A, Urban RJ. Troglitazone inhibits progesterone production in porcine granulosa cells. Endocrinology. 1998;139:4962–6. doi: 10.1210/en.139.12.4962.
    1. Gasic S, Nagamani M, Green A, Urban RJ. Troglitazone is a competitive inhibitor of 3beta-hydroxysteroid dehydrogenase enzyme in the ovary. Am J Obstet Gynecol. 2001;184:575–9. doi: 10.1067/mob.2001.111242.
    1. Mu YM, Yanase T, Nishi Y, Waseda N, Oda T, Tanaka A, et al. Insulin sensitizer, troglitazone, directly inhibits aromatase activity in human ovarian granulosa cells. Biochem Biophys Res Commun. 2000;271:710–3. doi: 10.1006/bbrc.2000.2701.
    1. Arlt W, Auchus RJ, Miller WL. Thiazolidinediones but not metformin directly inhibit the steroidogenic enzymes P450c17 and 3beta -hydroxysteroid dehydrogenase. J Biol Chem. 2001;276:16767–71. doi: 10.1074/jbc.M100040200.
    1. Seto-Young D, Paliou M, Schlosser J, Avtanski D, Park A, Patel P, et al. Direct thiazolidinedione action in the human ovary: insulin-independent and insulin-sensitizing effects on steroidogenesis and insulin-like growth factor binding protein-1 production. J Clin Endocrinol Metab. 2005;90:6099–105. doi: 10.1210/jc.2005-0469.

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit