17 alpha hydroxyprogesterone


Summary: A metabolite of PROGESTERONE with a hydroxyl group at the 17-alpha position. It serves as an intermediate in the biosynthesis of HYDROCORTISONE and GONADAL STEROID HORMONES.

Top Publications

  1. Rojas Marcos P, David R, Kohn B. Hormonal effects in infants conceived by assisted reproductive technology. Pediatrics. 2005;116:190-4 pubmed
  2. Rossi R, Tauchmanova L, Luciano A, Di Martino M, Battista C, del Viscovo L, et al. Subclinical Cushing's syndrome in patients with adrenal incidentaloma: clinical and biochemical features. J Clin Endocrinol Metab. 2000;85:1440-8 pubmed
    ..These findings support the hypothesis that clinically silent hypercortisolism is probably not completely asymptomatic. ..
  3. Joy S, Rhea D, Istwan N, Desch C, Stanziano G. The risk for preterm labor in women receiving 17 alpha-hydroxyprogesterone caproate prophylaxis for preterm birth prevention. Am J Perinatol. 2010;27:343-8 pubmed publisher
    ..5 [1.1, 2.1]). Women receiving 17P prophylaxis remain at increased risk for PTL and preterm birth. Patient education and surveillance for PTL symptoms may be warranted in women with a history of more than one prior preterm delivery. ..
  4. Lando V, Batista M, Nakamura I, Mazi C, Mendonca B, Brito V. Effects of long-term storage of filter paper blood samples on neonatal thyroid stimulating hormone, thyroxin and 17-alpha-hydroxyprogesterone measurements. J Med Screen. 2008;15:109-11 pubmed publisher
  5. Predieri B, Luisi S, Casarosa E, De Simone M, Balli F, Bernasconi S, et al. High basal serum allopregnanolone levels in overweight girls. Int J Obes (Lond). 2007;31:543-9 pubmed
    ..We can also speculate that in OW girls, who could manifest emotional and behavioral problems, a part of higher levels of this neuroactive steroid might act as gamma-aminobutyric acid agonist producing anxiolytic-sedative effects. ..
  6. Fedotcheva N, Teplova V, Fedotcheva T, Rzheznikov V, Shimanovskii N. Effect of progesterone and its synthetic analogues on the activity of mitochondrial permeability transition pore in isolated rat liver mitochondria. Biochem Pharmacol. 2009;78:1060-8 pubmed publisher
  7. Frisch H, Battelino T, Schober E, Baumgartner Parzer S, Nowotny P, Vierhapper H. Salt wasting in simple virilizing congenital adrenal hyperplasia. J Pediatr Endocrinol Metab. 2001;14:1649-55 pubmed
    ..Additional mineralocorticoid therapy should be considered in order to suppress PRC and reduce the glucocorticoid dose required for adequate control. ..
  8. Claahsen van der Grinten H, Otten B, Takahashi S, Meuleman E, Hulsbergen van de Kaa C, Sweep F, et al. Testicular adrenal rest tumors in adult males with congenital adrenal hyperplasia: evaluation of pituitary-gonadal function before and after successful testis-sparing surgery in eight patients. J Clin Endocrinol Metab. 2007;92:612-5 pubmed
    ..Intensifying glucocorticoid therapy does not always lead to tumor regression and improvement of testicular function. Recently, testis-sparing surgery was introduced for treatment of TART...
  9. Lee C, Tung Y, Hsiao P, Lee J, Tsai W. Clinical characteristics of Taiwanese children with congenital adrenal hyperplasia caused by 21-hydroxylase deficiency in the pre-screening era. J Formos Med Assoc. 2010;109:148-55 pubmed publisher
    ..Laboratory tests, including serum 17-hydroxyprogesterone, androstenedione, and testosterone levels are more sensitive than serum cortisol or dehydroepiandrosterone sulfate levels for diagnosing 21-OHD in prepubertal children. ..

More Information


  1. Korkhov V, Lesik E, Petrosian M, Ivanov A, Tapil skasia N. [Experimental progestogenic activity of novel derivatives of 17alpha-hydroxyprogesterone]. Eksp Klin Farmakol. 2003;66:36-8 pubmed
    ..In particular, AMOL isopropyl ester is capable of maintaining pregnancy in ovariectomized animals (Corner-Allen assay). ..
  2. Spong C, Meis P, Thom E, Sibai B, Dombrowski M, Moawad A, et al. Progesterone for prevention of recurrent preterm birth: impact of gestational age at previous delivery. Am J Obstet Gynecol. 2005;193:1127-31 pubmed
    ..17-OHP caproate therapy given to prevent recurrent PTB is associated with a prolongation of pregnancy overall, and especially for women with a previous spontaneous PTB at <34 weeks. ..
  3. Ludwig A, Goharian L, Dietze T, Tauchert S, Rudolf S, Diedrich K, et al. Impact of glycemic variations on the regulation of androgen metabolism in obese women with polycystic ovary syndrome. Fertil Steril. 2009;92:271-6 pubmed publisher
    ..This supports a gender difference regarding the counterregulatory hormone response to hypoglycemia. ..
  4. Straub R, Weidler C, Demmel B, Herrmann M, Kees F, Schmidt M, et al. Renal clearance and daily excretion of cortisol and adrenal androgens in patients with rheumatoid arthritis and systemic lupus erythematosus. Ann Rheum Dis. 2004;63:961-8 pubmed
    ..Decreased adrenal production or increased conversion or conjugation to downstream hormones are the most likely causes of inadequately low serum levels of adrenal hormones in RA and SLE. ..
  5. Minutti C, Lacey J, Magera M, Hahn S, McCann M, Schulze A, et al. Steroid profiling by tandem mass spectrometry improves the positive predictive value of newborn screening for congenital adrenal hyperplasia. J Clin Endocrinol Metab. 2004;89:3687-93 pubmed
    ..This would prevent unnecessary blood draws, medical evaluations, and stress to families. ..
  6. Panidis D, Farmakiotis D, Koliakos G, Rousso D, Kourtis A, Katsikis I, et al. Comparative study of plasma ghrelin levels in women with polycystic ovary syndrome, in hyperandrogenic women and in normal controls. Hum Reprod. 2005;20:2127-32 pubmed
    ..It is also likely that different clinical and biochemical manifestations of the syndrome are also associated with different ghrelin concentrations. ..
  7. Bonoli M, Varjo S, Wiedmer S, Riekkola M. Cationic lipid vesicles as coating precursors in capillary electrochromatography: separation of basic proteins and neutral steroids. J Chromatogr A. 2006;1119:163-9 pubmed
    ..In addition to basic proteins the DOTAP coating was found suitable under acidic conditions for the repeatable separation of neutral steroids. The potential of DOTAP as a carrier in background electrolyte solution was studied. ..
  8. Arase M, Waterman M, Kagawa N. Purification and characterization of bovine steroid 21-hydroxylase (P450c21) efficiently expressed in Escherichia coli. Biochem Biophys Res Commun. 2006;344:400-5 pubmed
    ..Truncation of the membrane anchor increases solubility of P450c21 facilitating expression of this protein in E. coli yielding sufficient quantities for both biochemical and biophysical studies. ..
  9. Lindén M, Holopainen J, Laukkanen A, Riekkola M, Wiedmer S. Cholesterol-rich membrane coatings for interaction studies in capillary electrophoresis: application to red blood cell lipid extracts. Electrophoresis. 2006;27:3988-98 pubmed
    ..Finally, the electrophoretic measurements revealed that a stable coating is formed when capillaries are coated with liposomes of RBC ghost lipids. ..
  10. Jeffcoate W. Assessment of corticosteroid replacement therapy in adults with adrenal insufficiency. Ann Clin Biochem. 1999;36 ( Pt 2):151-7 pubmed
    ..In such circumstances, a cortisol day curve is likely to be of more value than measurement of UFC. ..
  11. Järvelä I, Ruokonen A, Tekay A. Effect of rising hCG levels on the human corpus luteum during early pregnancy. Hum Reprod. 2008;23:2775-81 pubmed publisher
    ..The activity of the CL during pregnancy may be measured non-invasively by assessing its vasculature with three-dimensional ultrasonography. ..
  12. Cavarzere P, Samara Boustani D, Flechtner I, Dechaux M, Elie C, Tardy V, et al. Transient hyper-17-hydroxyprogesteronemia: a clinical subgroup of patients diagnosed at neonatal screening for congenital adrenal hyperplasia. Eur J Endocrinol. 2009;161:285-92 pubmed publisher
    ..No further investigations are necessary after birth in these newborns if 17-OHP levels decrease, other confirmatory tests such as ACTH-stimulation test or genotyping analysis are necessary only if symptoms appear. ..
  13. Lawnicka H, Kowalewicz Kulbat M, Sicinska P, Kazimierczuk Z, Grieb P, Stepien H. Anti-neoplastic effect of protein kinase CK2 inhibitor, 2-dimethylamino-4,5,6,7-tetrabromobenzimidazole (DMAT), on growth and hormonal activity of human adrenocortical carcinoma cell line (H295R) in vitro. Cell Tissue Res. 2010;340:371-9 pubmed publisher
    ..Thus, CK2 kinase activity is probably involved in human ACC endocrine activity and growth...
  14. Escobar Morreale H, San Millan J, Smith R, Sancho J, Witchel S. The presence of the 21-hydroxylase deficiency carrier status in hirsute women: phenotype-genotype correlations. Fertil Steril. 1999;72:629-38 pubmed
    ..The response of serum 17-hydroxyprogesterone to ACTH does not predict CYP21 carrier status. No clear concordance was found between the CYP21 genotype and the functional origin of androgen excess. ..
  15. Cutolo M, Straub R, Foppiani L, Prete C, Pulsatelli L, Sulli A, et al. Adrenal gland hypofunction in active polymyalgia rheumatica. effect of glucocorticoid treatment on adrenal hormones and interleukin 6. J Rheumatol. 2002;29:748-56 pubmed
    ..e., increased 17-OHP), at least in untreated patients. The 12 month glucocorticoid treatment of patients reduced the production of inflammatory mediators (i.e., IL-6) in a stable manner that persisted after glucocorticoids were tapered. ..
  16. Tsagarakis S, Tsigos C, Vassiliou V, Tsiotra P, Pratsinis H, Kletsas D, et al. Food-dependent androgen and cortisol secretion by a gastric inhibitory polypeptide-receptor expressive adrenocortical adenoma leading to hirsutism and subclinical Cushing's syndrome: in vivo and in vitro studies. J Clin Endocrinol Metab. 2001;86:583-9 pubmed
    ..Thus, aberrant expression of the GIP receptor does not exclusively involve cells of a zona fasciculata phenotype, as previously reported, but may also occur in other types of differentiated adrenocortical cells. ..
  17. Straub R, Härle P, Yamana S, Matsuda T, Takasugi K, Kishimoto T, et al. Anti-interleukin-6 receptor antibody therapy favors adrenal androgen secretion in patients with rheumatoid arthritis: a randomized, double-blind, placebo-controlled study. Arthritis Rheum. 2006;54:1778-85 pubmed
    ..This is another important indication that proinflammatory cytokines interfere with adrenal androgen steroidogenesis in patients with RA. ..
  18. Schneider F, Brüssow K, Kanitz E, Otten W, Tuchscherer A. Maternal reproductive hormone levels after repeated ACTH application to pregnant gilts. Anim Reprod Sci. 2004;81:313-27 pubmed
    ..However, these findings demonstrate that stress-related effects are dependent on the stage of pregnancy. The detected changes may affect feto-maternal interactions and, as a result, fetal reproductive development. ..
  19. Rauh M, Gröschl M, Rascher W, Dörr H. Automated, fast and sensitive quantification of 17 alpha-hydroxy-progesterone, androstenedione and testosterone by tandem mass spectrometry with on-line extraction. Steroids. 2006;71:450-8 pubmed
    ..The sensitivity and specificity of the LC-MS/MS method offer advantages over routine immunoassays due to the elimination of interferences especially for newborns, high throughput and short chromatographic run time. ..
  20. Hoepffner W, Schulze E, Bennek J, Keller E, Willgerodt H. Pregnancies in patients with congenital adrenal hyperplasia with complete or almost complete impairment of 21-hydroxylase activity. Fertil Steril. 2004;81:1314-21 pubmed
    ..Only the women treated with hydrocortisone alone did not become pregnant. When treated with a combination of glucocorticoids and mineralocorticoids, sexually active patients with the classic phenotype of CAH can become pregnant. ..
  21. Combs C, Garite T, Maurel K, Das A, Porto M. Failure of 17-hydroxyprogesterone to reduce neonatal morbidity or prolong triplet pregnancy: a double-blind, randomized clinical trial. Am J Obstet Gynecol. 2010;203:248.e1-9 pubmed publisher
    ..02). In triplet pregnancy, prophylactic treatment with 17P did not reduce neonatal morbidity or prolong gestation but was associated with increased midtrimester fetal loss. ..
  22. Falsetti L, Gambera A, Andrico S, Sartori E. Acne and hirsutism in polycystic ovary syndrome: clinical, endocrine-metabolic and ultrasonographic differences. Gynecol Endocrinol. 2002;16:275-84 pubmed
    ..Acne was associated only with the lowest 3alpha-androstanediol glucuronide levels. Therefore, two different pathogenetic mechanisms may play a role in the onset of acne and hirsutism. ..
  23. Bajpai A, Singhal T, Kabra M, Menon P. CNS germinoma in a boy with simple virilizing 21-hydroxylase deficiency and precocious puberty. J Pediatr Endocrinol Metab. 2002;15:335-7 pubmed
    ..Serum and CSF levels of human chorionic gonadotropin (hCG) and alphafetoprotein (AFP) were elevated, confirming the diagnosis of germinoma. ..
  24. Christakoudi S, Cowan D, Taylor N. Steroids excreted in urine by neonates with 21-hydroxylase deficiency: characterization, using GC-MS and GC-MS/MS, of the D-ring and side chain structure of pregnanes and pregnenes. Steroids. 2010;75:34-52 pubmed publisher
    ..We conclude that GC-MS combined with GC-MS/MS allows reliable identification of the structure of the D-ring and side chain of pregnane(ene)s without prior isolation, even when in low concentrations in urine. ..
  25. Wikiera B, B Wasikowa R. [Adrenal function in girls with hirsutism]. Endokrynol Diabetol Chor Przemiany Materii Wieku Rozw. 2005;11:27-31 pubmed
    ..High 17OHP and normal cortisol level after Synacthen administration in PCOS girls point that activity of enzymes involved in 17OHP production is augmented. ..
  26. Groschl M, Rauh M, Schmid P, Dorr H. Relationship between salivary progesterone, 17-hydroxyprogesterone, and cortisol levels throughout the normal menstrual cycle of healthy postmenarcheal girls. Fertil Steril. 2001;76:615-7 pubmed
    ..74; P<.001), although F did not show any correlation to P or 17-OHP. Changes in salivary 17-OHP levels throughout the menstrual cycle reflect ovarian but not adrenal function. ..
  27. Longui C, Zlochevsky E, Bachega T, Monte O. Adrenal steroids synthesis during acute infectious diseases in infants. J Pediatr Endocrinol Metab. 2002;15:1515-23 pubmed
    ..We suggest that if 17OHP elevation is not characteristic of SL-CAH, glucocorticoid therapy should be started and an ACTH test should be performed after recovery before ruling out this pathology. ..
  28. Shibayama Y, Higashi T, Shimada K, Kashimada K, Onishi T, Ono M, et al. Liquid chromatography-tandem mass spectrometric method for determination of salivary 17alpha-hydroxyprogesterone: a noninvasive tool for evaluating efficacy of hormone replacement therapy in congenital adrenal hyperplasia. J Chromatogr B Analyt Technol Biomed Life Sci. 2008;867:49-56 pubmed publisher
    ..The result from the salivary 17OHP measurement in patients with congenital adrenal hyperplasia demonstrated that the proposed method is very useful for monitoring of the therapeutic efficacy during hormone replacement therapy. ..
  29. Bruining H, Bootsma A, Koper J, Bonjer J, de Jong F, Lamberts S. Fertility and body composition after laparoscopic bilateral adrenalectomy in a 30-year-old female with congenital adrenal hyperplasia. J Clin Endocrinol Metab. 2001;86:482-4 pubmed
    ..The introduction of laparoscopic techniques may give an impulse to the application of surgical therapy at a larger scale in patients with 21-hydroxylase deficiency who are difficult to treat with adrenal suppression therapy. ..
  30. Speiser P. Improving neonatal screening for congenital adrenal hyperplasia. J Clin Endocrinol Metab. 2004;89:3685-6 pubmed
  31. Järvelä I, Niinimäki M, Martikainen H, Ruokonen A, Tapanainen J. Ovarian response to the human chorionic gonadotrophin stimulation test in normal ovulatory women: the impact of regressing corpus luteum. Fertil Steril. 2007;87:1122-30 pubmed
  32. Dissen G, Garcia Rudaz C, Paredes A, Mayer C, Mayerhofer A, Ojeda S. Excessive ovarian production of nerve growth factor facilitates development of cystic ovarian morphology in mice and is a feature of polycystic ovarian syndrome in humans. Endocrinology. 2009;150:2906-14 pubmed publisher
  33. Hugues J, Theron Gerard L, Coussieu C, Pasquier M, Dewailly D, Cedrin Durnerin I. Assessment of theca cell function prior to controlled ovarian stimulation: the predictive value of serum basal/stimulated steroid levels. Hum Reprod. 2010;25:228-34 pubmed publisher
    ..Serum androgen levels following GAST are correlated with AFC and ovarian response to FSH. Serum T is a less sensitive marker of theca cell function than 17-OHP. ..
  34. Caputo V, Fiorella S, Curiale S, Caputo A, Niceta M. Refractory acne and 21-hydroxylase deficiency in a selected group of female patients. Dermatology. 2010;220:121-7 pubmed publisher
    ..Persistent acne can be the unique presenting sign of non-classical 21-OHD. Evaluation of CYP21 gene mutations may identify female carriers or patients for genetic counselling. ..
  35. Manuck T. 17-alpha hydroxyprogesterone caproate for preterm birth prevention: Where have we been, how did we get here, and where are we going?. Semin Perinatol. 2017;41:461-467 pubmed publisher
  36. Orvieto R, Yulzari Roll V, La Marca A, Ashkenazi J, Fisch B. Serum androgen levels in patients undergoing controlled ovarian hyperstimulation for in vitro fertilization cycles. Gynecol Endocrinol. 2005;21:218-22 pubmed
    ..Although the E(2)/testosterone ratio correlates with the number of oocytes retrieved, androgen levels do not. ..
  37. Cragun D, Trumpy S, Shackleton C, Kelley R, Leslie N, Mulrooney N, et al. Undetectable maternal serum uE3 and postnatal abnormal sterol and steroid metabolism in Antley-Bixler syndrome. Am J Med Genet A. 2004;129A:1-7 pubmed
  38. Völkl T, Simm D, Körner A, Rascher W, Kiess W, Kratzsch J, et al. Does an altered leptin axis play a role in obesity among children and adolescents with classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency?. Eur J Endocrinol. 2009;160:239-47 pubmed publisher
    ..Our data show that an altered leptin axis with normal serum leptin concentrations but decreased sOB-R serum levels may contribute to the increased risk of overweight and obesity in CAH. ..
  39. Li L, Lin T. Interacting influence of potassium and polychlorinated biphenyl on cortisol and aldosterone biosynthesis. Toxicol Appl Pharmacol. 2007;220:252-61 pubmed
    ..These data demonstrated that potassium differentially enhanced the potency of PCB126 to induce CYP11B1- and CYP11B2-mediated steroidogenesis. ..
  40. Trakakis E, Chryssikopoulos A, Sarandakou A, Phocas I, Rizos D, Gregoriou O, et al. Hypothalamic-pituitary-thyroidal axis dysfunction and cortisol secretion in patients with nonclassical congenital adrenal hyperplasia. Int J Fertil Womens Med. 2001;46:37-41 pubmed
    ..The results of this study support a dysfunction of the hypothalamic-pituitary-thyroidal axis due to altered ACTH secretion patterns. ..
  41. Kizildere S, Gluck T, Zietz B, Scholmerich J, Straub R. During a corticotropin-releasing hormone test in healthy subjects, administration of a beta-adrenergic antagonist induced secretion of cortisol and dehydroepiandrosterone sulfate and inhibited secretion of ACTH. Eur J Endocrinol. 2003;148:45-53 pubmed
    ..Sympathetic hyperactivity may be a common denominator for low levels of DHEAS in inflammatory and non-inflammatory diseases. ..
  42. Pall M, Azziz R, Beires J, Pignatelli D. The phenotype of hirsute women: a comparison of polycystic ovary syndrome and 21-hydroxylase-deficient nonclassic adrenal hyperplasia. Fertil Steril. 2010;94:684-9 pubmed publisher
  43. Naiki Y, Nanao K, Hasegawa Y. Adrenocorticotropic hormone and 17-hydroxyprogesterone levels during high-dose glucocorticoid supplement for the management of clitoroplasty of CYP21A2 deficiency. Endocr J. 2004;51:367-73 pubmed
    ..ACTH and 17OHP levels were completely suppressed throughout operation, indicating that this kind of additional pretreatment is more effective approach. ..
  44. Dauber A, Kellogg M, Majzoub J. Monitoring of therapy in congenital adrenal hyperplasia. Clin Chem. 2010;56:1245-51 pubmed publisher
    ..Assays of daily hormonal profiles from saliva or blood spots offer a more detailed assessment of therapeutic control, although salivary assays have variable quality. ..
  45. Uncu G, Sözer M, Develioglu O, Cengiz C. The role of plasma renin activity in distinguishing patients with polycystic ovary syndrome (PCOS) from oligomenorrheic patients without PCOS. Gynecol Endocrinol. 2002;16:447-52 pubmed
    ..However, it can be used together with other variables to diagnose women with PCOS and to distinguish non-PCOS oligomenorrheic women from those with PCOS. ..
  46. Strowitzki T, Halser B, Demant T. Body fat distribution, insulin sensitivity, ovarian dysfunction and serum lipoproteins in patients with polycystic ovary syndrome. Gynecol Endocrinol. 2002;16:45-51 pubmed
    ..It is concluded that PCOS patients show metabolic abnormalities combined with a more adroid type of adiposity when compared to cyclic controls of similar BMI. ..
  47. Nordenstrom A, Wedell A, Hagenfeldt L, Marcus C, Larsson A. Neonatal screening for congenital adrenal hyperplasia: 17-hydroxyprogesterone levels and CYP21 genotypes in preterm infants. Pediatrics. 2001;108:E68 pubmed
    ..It is clear that neonatal screening cannot detect all infants with CAH. Some milder forms of the disease, just like in the past, will have to be diagnosed on the basis of clinical signs and symptoms. ..
  48. Piltonen T, Koivunen R, Ruokonen A, Tapanainen J. Ovarian age-related responsiveness to human chorionic gonadotropin. J Clin Endocrinol Metab. 2003;88:3327-32 pubmed
    ..Despite that, circulating E(2) levels remain normal for years, possibly due to compensatory mechanisms, reflected by the gradual rise in serum FSH levels. ..
  49. Chang R. A practical approach to the diagnosis of polycystic ovary syndrome. Am J Obstet Gynecol. 2004;191:713-7 pubmed
    ..In addition, in the obese individual, determinations of glucose and insulin levels, as well as a lipid profile, are highly recommended. ..
  50. Kreze A. [Adrenal gland incidentaloma]. Vnitr Lek. 2001;47:840-6 pubmed
    ..2% (2 patients) a pheochromocytoma and in one patient (1.6%) impaired secretion of 17-hydroxyprogesterone. Functionally active incidentalomas accounted for one quarter of the investigated group. ..
  51. Straub R, Tanko L, Christiansen C, Larsen P, Jessop D. Higher physical activity is associated with increased androgens, low interleukin 6 and less aortic calcification in peripheral obese elderly women. J Endocrinol. 2008;199:61-8 pubmed publisher
    ..Since androgens inhibit IL6 secretion, the activity-induced increase of these hormones might be an anti-atherogenic signal. ..
  52. Dumic M, Ille J, Zunec R, Plavsic V, Francetic I, Skrabic V, et al. Nonclassic 21-hydroxylase deficiency in Croatia. J Pediatr Endocrinol Metab. 2004;17:157-64 pubmed
    ..Clinical and genetic analysis confirmed nonclassic 21-OH deficiency in our Croatian sample of ten males and eight females. This study shows that genotype does not necessarily predict fertility status in our group of affected patients. ..
  53. Atzeni F, Straub R, Cutolo M, Sarzi Puttini P. Psoriatic arthritis: clinical improvement and correlation with hormone axes in etanercept-treated patients. Ann N Y Acad Sci. 2010;1193:176-8 pubmed publisher
    ..However, the greater increase in serum cortisol in comparison with serum 17OHP or ASD was related to clinical improvement, which indicates that the improvement was more related to the higher cortisol levels...