Hostname: page-component-745bb68f8f-f46jp Total loading time: 0 Render date: 2025-02-05T23:54:14.553Z Has data issue: false hasContentIssue false
  • English
  • Français

Pathogenesis and treatment of hirsutism in late-onset congenital adrenal hyperplasia

Published online by Cambridge University Press:  03 June 2009

E Carmina
E Carmina*
Affiliation:
Department of Endocrinology, University of Palermo, Palermo, Italy
*
Visiting Research Scientist, Department of Obstetrics and Gynecology, Columbia University Medical Centre, 622 W 168th Street, New York, NY 10032, USA.
Get access Rights & Permissions [Opens in a new window]

Extract

Late-onset or nonclassic hyperandrogenic congenital adrenal hyperplasia (CAH) is an attenuated deficiency of 21-hydroxylase, 3β-ol-hydroxysteroid dehydrogenase or 11β-hydroxylase which presents during childhood or adolescence and leads to an increased secretion of adrenal androgens. Many reviews of the genetic or hormonal characteristics of these syndromes have been published, but relatively little attention has been paid to the pathogenesis and treatment of hirsutism which, in most young women, is the main complaint. In fact, it is generally assumed that the hirsutism is strictly related to the increased secretion of adrenal androgens and that glucocorticoids are the treatment of choice. However, some recent studies have shown that the ovary contributes to the hyperandrogenism of these patients and some alternative therapies have been proposed. This forms the matter of the present review.

Type
Articles
Information
Reproductive Medicine Review , Volume 4 , Issue 3 , October 1995 , pp. 179 - 187
Copyright
Copyright © Cambridge University Press 1995

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1New, MI. Non classical 21-hydroxylase deficiency. In: Dunaif, A, Givens, JR, Haseltine, FP, Merriam, GR eds. Polycystic ovary syndrome. Oxford: Blackwell Scientific, 1992: 145–61.Google Scholar
2Lobo, RA, Goebelsmann, U. Adult manifestation of congenital adrenal hyperplasia due to incomplete 21-hydroxylase deficiency mimicking polycystic ovarian disease. Am J Obstet Gynecol 1980; 138: 720–26.CrossRefGoogle ScholarPubMed
3Bouchard, P, Kuttenn, F, Mowszowicz, I, Schaison, G, Raux-Eurin, MC, Mauvais-Jarvis, P. Congenital adrenal hyperplasia due to a partial 21-hydroxylase deficiency, a study of five cases. Acta Endocrinol (Copenh) 1981; 96: 107–11.Google ScholarPubMed
4Carmina, E, Gagliano, AM, Rosato, F, Maggiore, M, Jannì, A. The endocrine pattern of late onset adrenal hyperplasia (21-hydroxylase deficiency). J Endocrinol Invest 1984; 7: 89–92.CrossRefGoogle ScholarPubMed
5Dewailly, D, Vantyghem-Haudiquet, MC, Sainsard, C et al. Clinical and biological phenotypes in late onset 21-hydroxylase deficiency. J Clin Endocrinol Metab 1986; 63: 418–23.CrossRefGoogle ScholarPubMed
6Speiser, PW, New, MI. Genotype and hormonal phenotype in nonclassical 21-hydroxylase deficiency. J Clin Endocrinol Metab 1987; 64: 86–91.CrossRefGoogle ScholarPubMed
7Lobo, RA, Goebelsmann, U. Evidence for reduced 3-beta-ol-hydroxysteroid-dehydrogenase activity in some hirsute women thought to have polycystic ovary syndrome. J Clin Endocrinol Metab 1981; 53: 394–98.CrossRefGoogle ScholarPubMed
8Pang, S, Lerner, AJ, Stoner, E et al. Late onset adrenal steroid 3β-hydroxysteroid-dehydrogenase deficiency. A cause of hirsutism in pubertal and postpubertal women. J Clin Endocrinol Metab 1985; 60: 426–38.CrossRefGoogle Scholar
9Carmina, E, Rosato, F, Caputo, A, Jannì, A. Late onset 3β-ol-hydroxysteroid dehydrogenase deficiency: prevalence, clinical presentation and endocrine pattern. Acta Eur Fertil 1985; 16: 427–30.Google Scholar
10Chatelineau, G, Breralt, J, Fiet, J, Julian, R, Dreux, C, Canivet, J. Adrenocortical 11β-hydroxylase defect in adult women with postmenarchial onset of symptoms. J Clin Endocrinol Metab 1980; 51; 287–92Google Scholar
11Carmina, E, Malizia, G, Pagano, M, Jannì, A. Prevalence of late onset 11β-hydroxylase deficiency in hirsute patients. J Endocrinol Invest 1988; 11: 595–98.CrossRefGoogle Scholar
12Carmina, E, Lobo, RA. Ovarian suppression reduces clinical and endocrine expression of late-onset congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Fertil Steril 1994; 62: 738–43.CrossRefGoogle ScholarPubMed
13Carmina, E, Stanczyk, FZ, Chang, L, Miles, RA, Lobo, RA. The ratio of androstenedione: 11-hydroxyandrostenedione is an important marker of adrenal androgen excess in women. Fertil Steril 1992; 58; 148–52.CrossRefGoogle ScholarPubMed
14Gadir, AA, Khatim, MS, Mowafi, RS, Alnase, HMI, Muharib, NS, Shaw, RW. Implications of ultrasonically diagnosed polycystic ovaries. II. Studies of dynamics and pulsatile hormonal patterns. Hum Reprod 1992; 7: 458–61.CrossRefGoogle ScholarPubMed
15Lobo, RA. The syndrome of hyperandrogenic chronic anovulation. In: Mishell, DR, Davajan, V, Lobo, RA eds. Infertility, contraception and reproductive endocrinology. Oxford: Blackwell Scientific, 1991: 447–87.Google Scholar
16Polson, DW, Adams, J, Wadsworth, J, Franks, S. Polycystic ovaries – a common finding in normal women. Lancet 1988; i: 870–73.CrossRefGoogle Scholar
17Levin, JH, Carmina, E, Lobo, RA. Is the inappropriate gonadotropin secretion of patients with polycystic ovary syndrome similar to that of patients with adult onset congenital adrenal hyperplasia? Fertil Steril 1991; 56: 635–40.CrossRefGoogle ScholarPubMed
18Lobo, RA, Granger, L, Goebelsmann, U, Mishell, DR Jr. Elevations in unbound serum estradiol as a possible mechanism for inappropriate gonadotropin secretion in women with polycystic ovary syndrome. J Clin Endocrinol Metab 1981; 52: 156–61.CrossRefGoogle Scholar
19Speiser, PW, Serrat, J, New, MI, Gertner, JM. Insulin insensitivity in adrenal hyperplasia due to nonclassical steroid 21-hydroxylase deficiency. J Clin Endocrinol Metab 1992; 75: 1421–24.Google ScholarPubMed
20Barbieri, RL, Smith, S, Ryan, KJ. The role of hyperinsulinemia in the pathogenesis of ovarian hyperandrogenism. Fertil Steril 1988; 50: 197–202.Google ScholarPubMed
21Cara, JF, Rosenfield, RL. Insulin-like growth factor I and insulin potentiate luteinizing hormone induced androgen synthesis by rat ovarian thecal-interstitial cells. Endocrinology 1988; 123: 733–39.CrossRefGoogle ScholarPubMed
22Suikkari, AM, Koivisto, V, Rutanen, EM, Yki, Jarvinen H, Karonen, SL, Seppala, M. Insulin regulates the serum levels of low molecular weight insulin-like growth factor binding protein. J Clin Endocrinol Metab 1988; 66: 266–72.CrossRefGoogle ScholarPubMed
23Carmina, E, Lobo, RA. Pituitary-adrenal responses to corticotropin-releasing factor in late onset 21-hydroxylase deficiency. Fertil Steril 1990; 54: 79–83.CrossRefGoogle ScholarPubMed
24Ditkoff, EC, Fruzzetti, F, Chang, L, Stanczyk, FZ, Lobo, RA. The impact of estrogen on adrenal androgen sensitivity and secretion in polycystic ovary syndrome. J Clin Endocrinol Metab 1995; 80: 603–607.Google ScholarPubMed
25Casson, PR, Buster, JE, Anderson, RN. Activin inhibits adrenal steroidogenesis in a bovine cell culture modal. 41st Annual Meeting of the Society Gynecological Investigation, Chicago, IL, USA, 1994: Abstract 235, pg 312.Google Scholar
26Penhoat, A, Jaillard, C, Saez, JM. Synergistic effects of corticotropin and insulin-like growth factor I on corticotropin receptors and corticotropin responsiveness in cultured bovine adenomatose cells. Biochem Biophys Res Commun 1989; 165: 355–59.CrossRefGoogle Scholar
27Mesuiano, S, Fujimoto, V, Nelson, LR, Jaffe, RB. ACTH and insulin-like growth factor II modulate ACTH receptor expression in human fetal adrenal cortical cells. 41st Annual Meeting of the Society of Gynecological Investigation, Chicago, IL, USA, 1994: Abstract 21, pg 97.Google Scholar
28Mauvais, Jarvis P. Regulation of androgen receptor and 5α-reductase in the skin of normal and hirsute women. Clin Endocrinol Metab 1986; 15: 307–17.CrossRefGoogle Scholar
29Lobo, RA: Hirsutism, alopecia and acne. In: Becker, KL ed. Principles and practice of endocrinology and metabolism. Philadelphia, PA: Lippincott, 1990: 834–918.Google Scholar
30Wahe, M, Antonipillai, I, Horton, R. TGF-β superfamily have different effects on steroid 5α-reductase activity. 75th Annual Meeting of the Endocrinology Society, Las Vegas, NV, USA, 1993: Abstract 1936, pg 534.Google Scholar
31Kuttenn, F, Coullin, PH, Girard, F et al. Late onset adrenal hyperplasia in hirsutism. N Engl J Med 1985; 313: 224–28.CrossRefGoogle ScholarPubMed
32Pang, S, Wang, M, Jeffries, S, Riddick, L, Clark, A, Estrada, E. Normal and elevated 3α-androstenediol glucuronide concentrations in women with various causes of hirsutism and its correlation with degree of hirsutism and androgen levels. J Clin Endocrinol Metab 1992; 75: 243–48.Google Scholar
33Carmina, E, Gentzschein, E, Standczyk, FZ, Lobo, RA. Substrate dependency of C19 conjugates in hirsute hyperandrogenic women and the influence of adrenal androgen. Hum Reprod 1995; 10: 299–303.CrossRefGoogle ScholarPubMed
34Hatch, R, Rosenfield, RL, Kim, MH, Trodway, D.Hirsutism: implications, etiology and treatment. Am J Obstet Gynecol 1981; 140: 815–30.CrossRefGoogle Scholar
35Spitzer, P, Billaud, L, Thalabard, JC, Birman, P, Mowszowicz, I, Raux-Demay, MC. Cyproterone acetate versus hydrocortisone treatment in late onset adrenal hyperplasia. J Clin Endocrinol Metab 1990; 70: 642–46.CrossRefGoogle Scholar
36Azziz, R, Zacur, HA. 21-Hydroxylase deficiency in female hyperandrogenism: screening and diagnosis. J Clin Endocrinol Metab 1989; 69: 577–83.CrossRefGoogle ScholarPubMed
37Rittmaster, RS, Loriaux, DL, Cutler, GB. Sensitivity of cortisol and adrenal androgens to dexamethasone suppression in hirsute women. J Clin Endocrinol Metab 1985; 61: 462–66.CrossRefGoogle ScholarPubMed
38Carmina, E, Caputo, A, Malizia, G, Jann`, A. Long term dexamethasone treatment of hirsutism. In: Genazzani, AR, Volpe, A, Facchinetti, F eds. Research on gynecologycal endocrinology. Carnforth, UK: Parthenon, 1987: 205–208.Google Scholar
39Carmina, E, Lobo, RA. Peripheral androgen blockade versus glandular suppression in the treatment of hirsutism. Obstet Gynecol 1991; 78: 845–49.Google ScholarPubMed
40Pittaway, DE, Mason, WS, Colston-Wentz, A. Spironolactone in combination drug therapy for unresponsive hirsutism. Fertil Steril 1985; 43: 878–82.CrossRefGoogle ScholarPubMed
41Carmina, E, Jannì, A, Lobo, RA. Physiological estrogen replacement may enhance the effectiveness of the gonadotropin releasing hormone agonist in the treatment of hirsutism. J Clin Endocrinol Metab 1994; 78: 126–30.Google ScholarPubMed
42Carr, BB, Breslau, NA, Givens, C, Byrd, W, Barnett-Hamm, C, Marshburn, PB. Oral contraceptive pills, gonadotropin releasing hormone agonists, or use in combination for treatment of hirsutism/a clinical research center study. J Clin Endocrinol Metab 1995; 80: 1169–78.Google ScholarPubMed
43Kuttenn, F, Rigaud, C, Wright, F, Mauvais-Jarvis, P. Treatment of hirsutism by oral cyproterone acetate and percutaneous estradiol. J Clin Endocrinol Metab 1980; 51: 1107–11.CrossRefGoogle ScholarPubMed
44Marconides, JAM, Wajchenberg, BL, Minanni, SL, Samojmik, E, Luthold, WW, Kirschner, MA. Treatment of hirsutism in women with flutamide. Fertil Steril 1992; 57: 543–47.CrossRefGoogle Scholar
45Wong, IL, Morris, RS, Chang, L, Spahn, MA, Stanczyk, FZ, Lobo, RA. A prospective randomized trial comparing finasteride to spironolactone in the treatment of hirsute women. J Clin Endocrinol Metab 1995; 80: 233–38.Google ScholarPubMed