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Gender Differences in Studies of Thyroid Function and Major Depression
CITATION:  MacQueen, G.M. and Joffe, R.T.  (2002). A Review of Gender Differences in Studies of Thyroid Function and Major Depression. Psychiatric Annals; Aug 32, 8.

ABSTRACT:   Women have a greater lifetime risk of depression than men, and they appear to be more vulnerable to mood changes during times of known hormonal fluctuation, such as the luteal phase of the menstrual cycle,' the postpartum period,'- and possibly during menopause.3 Women also have an increased vulnerability to thyroid disease when significant hormonal adjustments occur.' Additionally, thyroid illness is commonly known to induce mood symptoms.' This has led to considerable study on the relationship between depression, sex, and thyroid function, with a number of studies highlighting differences between depressed men and women on both response to thyroid challenge during depression and use of thyroid hormones as adjunctive treatments in depression. It has also led to interest in the possible association of thyroid dysfunction and depression related to women's reproductive phases, such as late luteal phase disorder and postpartum depression. Studies examining these relationships are reviewed below.

The strongest data for an association between sex, thyroid function, and depression are found in TRH stimulation studies (where men more often demonstrate a blunted response) and in T3 acceleration studies, in which women are more likely to respond if T3 supplements an antidepressant at initiation.


1. Dalton K. The Premenstrual Syndrome. London: Heineman Medical; 1964.

2. Broekington IF, Kumar R. Motherhood and Mental Illness. London: Academic Press; 1982.

3. Winokur G. Depression in the menopause. Am J Psychiatry. 1973;130:92-96.

4. Wieck A. Endocrine aspects of postnatal disorders. Ballieres Best Pract Res Clin Obstet Gynaecol. 1989;3:857-877.

5. Whybrow P Prange Al. A hypothesis of thyroid-catecholamine-receptor interaction: its relevance to affective illness. Arch Gen Psychiatry. 1981;38:106-113.

6. Kastin Al, Ehrensing RH, Schlach DS, Anderson MS. Improvement in mental depression with decreased thyrotropin response after administration of thyrotropinreleasing hormone. Lancet. 1972;2:740-742.

7. Loosen PT, Prange Al Jr. Serum thyrotropin response to thyrotropin-releasing hormone in psychiatric patients: a review. Am J Psychiatry. 1982;31:1369-1374.

8. Loosen PT. The TRH-induced TSH response in psychiatric patients: a possible neuroendocrine marker. Ps ychoneu roendocri nology. 1985;10:237-260.

9. Nemeroff CB, Bissette G, Martin J13, Brazeau P, Vale W, Kizer JS, et al. Effect of chronic treatment with thyrotropin-releasing hormone (TRH) or an analog of TRH (linear beta-alanine TRH) on the hypothalamic-pituitarythyroid axis. Neuroendocrinology. 1980;30:193-199.

10. Hinkle PM, Tashjian AH Jr. Thyrotropin-releasing hormone regulates the number of its own receptors in the GH3 strain of pituitary cells in culture. Biochemistry. 1975;14:3845-3851.

11. Roy A, Karoum F, Linnoila M. Thyrotropin releasing hormone test in unipolar depressed patients and controls: relationship to clinical and biologic variables. Acta Psychiatr Scand. 1988;77:155-159.

12. Unden F, Ljunggren JG, Kjellman BF, Beck-Friis J, Wetterberg L. Unaltered 24 h serum PRL levels and PRL response to TRH in contrast to decreased 24 h serum TSH levels and TSH response to TRH in major depressive disorder. Acta Psychiatr Scand. 1987;75:131-138.

13. Gold PW, Goodwin FK, Wehr T, Rebar R. Pituitary thyrotropin response to thyrotropin-releasing hormone in affective illness: relationship to spinal fluid amine metabolites. Ain J Psychiatry. 1977;134:1028-1031.

14. Extein I, Pottash AL, Gold MS, Silver JM. Thyroid-stimulating hormone response to thyrotropin-releasing hormone in unipolar depression before and after clinical improvement. Psychiatry Research. 1982;6:161-169.

15. Kirkegaard C, Bjorum N, Cohn D, Faber J, Lauridsen UB, Nekup J. Studies on the influence of biogenic amines and psychoactive drugs on the prognostic value of the TRH stimulation test in endogenous depression. Ps yehoneuroendocrinology. 1977;2:131-136.

16. Kirkegaard C, Faber J. Influence of free thyroid levels on the TSH response to TRH in endogenous depression. Psychoendocri nol ogy. 1986;11;491-497.

17. Langer G, Koinig G, Hatzinger R, Shonbeck G, Resch F, Aschauer H, et al. Response to thyrotropin and thyrotropin-releasing hormone as predictor of treatment out-come: prediction of recovery and relapse in treatment with antidepressants and neuroleptics. Arch Gen Psychiatry. 1986;43:861-868.

18. Levy A, Stern S. DST and TRH stimulation test in mood disorder subtypes. Am J Psychiatry. 1987;144:472-475.

19. Orth DN, Shelton RC, Nicholson WE, Beck-Peccoz P, Tomarken AJ, Persani L, et al. Serum thvrotropin concentrations and bioactivity during sleep deprivation in depression. Arch Getz Psychiatry. 2001;58:77-83.

20. Unden F, Ljunggren JG, Kjellman B, Beck-Friis J, Wetterberg L. Twentv-four-hour serum levels of T; and T3 in relation to decreased TSH serum levels and decreased TSH response to TRH in affective disorders. Acta Psychiatr Scand. 1986;73:358-365.

21. Wolkin A, Peselow ED, Smith M, Lautin A, Kahn I, Rotrosen J. TRH test abnormalities in psychiatric disorders. ],Affect Disord. 1984;6:273-281.

22. Garbutt JC, Mayo JP, Little KY, Gillette GM, Mason GA, Dew B, et al. Dose-response studies with protirelin. Arch Gen Psychiatry. 1994;51:875-883.

21 Mongioi A, Aliffi A, Vicari E, Coniglione F, Scapagnini U, D'Agata R. Down-regulation of prolactin secretion in men during continuous thyrotropin-releasing hormone infusion: evidence for induction of pituitary desensitization by continuous TRH administration. J Clin Endocrinol Metab. 1983;56:904-907.

24. Frey HM, Haug E. Effect of prolonged oral administration of TRH on plasma levels of thyrotrophin and prolactin in normal individuals and in patients with primary hypothyroidism. Acta Endocrinologica (Copenh). 1977;85:744-752.

25. Roy-Byrne PP, Rubinow DR, Hoban MC, Grover GN, Blank D. TSH and prolactin responses to TRH in patients with premenstrual syndrome. Am J Psychiatry. 1987;144:480-484.

26. Casper RF, Patel-Christopher A, Powell AM. Thyrotropin and prolactin responses to thyrotropin-releasing hormone in premenstrual syndrome. J Clin Endocrinol Metab. 1989;68:608-612.

27. Nikolai TF, Mulligan GM, Gribble RK, Harkins PG, Meier PR, Roberts RC. Thyroid function and treatment in pre-menstrual syndrome. J Clin Endocrinol Metab. 1990;70:1108-1113.

28. Brayshaw NB, Brayshaw DD. Thyroid hypofunction in
premenstrual syndrome. N Engl J Med. 1986;315:1486-1487.

29. Korzekwa MI, Lamont JA, Steiner M. Late luteal phase
dysphoric disorder and the thyroid axis revisited. J ClinEndocrinol Metab. 1996;81:2280-2284.

30. Tunbridge WM, Evered DC, Hall R, Appleton D, Brewis M, Clark F, et al. The spectrum of thyroid disease in a community: the Whickham survey. Clin Endocrinol Qxf). 1977;7:481-493.

31. Pedersen CA, Stern RA, Pate J, Senger MA, Bowes WA, Mason GA. Thyroid and adrenal measures during late pregnancy and the puerperium in women who have been major depressed or who become dysphoric postpartum. J Affect Disord. 1993,29:201-211.

32. Hopkins J, Marcus M, Campbell SB. Postpartum depression: a critical review. Psychol Bull. 1984;95:498-515.

33. Inwood DG, ed. The spectrum of postpartum psychiatric disorders: In: Recent Advances in Postpartum Psychiatric Disorders. Washington, DC: American Psychiatric Association; 1985:1-18.

34. Paffenbarger RA. Epidemiological aspects of mental illness associated with childbearing. In: Brockington IF, Kumar R, eds. Motherhood and Mental Illness. Philadelphia: WB Saunders, 1982.

35. Hendrick V, Altshuler LL, Suri R. Hormonal changes in the postpartum and implications for postpartum depression. Psychosomatics. 1998;39:93-101.

36. Gotlib IH, Whitten VE, Mount JH, Milne K, Corsy NI. Prevalence rates and demographic characteristics associated with depression in pregnancy and the postpartum state. J Consult Clin Psychol. 1989;2:69-74.

37. O'Hara MW, Zekoski EM, Philipps LH, Wright EJ. Controlled prospective study of postpartum mood disorders: comparison of childbearing and nonchildbearing women. J Abnorm Psychol. 1990;99:3-15.

38. Pfost KS, Stevens MJ, Lum CU. The relationship of demo-graphic variables, antepartum depression, and stress to postpartum depression. J Clin Psychol. 1990;46:588-592.

39. Zuckerman BS, Beardslee WR. Maternal depression: a concern for pediatricians. Pediatrics. 1987;79:110-117.

40. O'Hara MW, Schlechte JA, Lewis DA, Varner MW. Controlled prospective study of postpartum mood disorders: psychological, environmental and hormonal variables. J Abnorm Psychol. 1991;100:63-73.

41. Paykel ES, Emms EM, Fletcher J, Rassaby ES. Life events and social support in puerperal depression. Br J Psychiatry. 1980;136:339-346.

42. Stewart DE, Addison AM, Robinson GE, Joffe R, Burrow GN, Olmsted MP Thyroid function in psychosis following childbirth. Am J Psychiatry. 1988;145:1579-1581.

43. Harris B, Fung H, Johns S, Kologlu M, Bhatti R, McGregor AM, et al. Transient post-partum thyroid dysfunction and thyroid antibodies and postnatal depression. J Affect Disord. 1989,17:243-249.

44. Pop VJ, deRooy HA, Vader HL, van der Heide D, van Son M, Komproe IH, et al. Postpartum thyroid dysfunction and depression in an unelected population [published correction appears in N Eng J Med. 1991;325:371]. N Eng J Med. 1991;324:1815-1816.

45. Harris B, Othman S, Davies JA, Weppner GJ, Richards CJ, Newcombe RG, et al. Association between postpartum thyroid dysfunction and thyroid antibodies and depression. Br Med J. 1992;305:152-156.

46. Kent GN, Stuckey BG, Allen JR, Lambert T, Gee V. Postpartum thyroid dysfunction: clinical assessment and relationship to psychiatric affective morbidity. Clin Endocrinol (Ox f). 1999;51:429-438.

47. Lucas A, Pizarro E, Granada ML, Salinas I, Foz M, Sanmarti A. Postpartum thyroiditis: epidemiology and
clinical evolution in a nonsetected population. Thyroid. 2000;10:71-77.

48. Muller AF, Drexhage HA, Berhout A. Postpartum thyroiditis and autoimmune thyroiditis in women of child-bearing age: recent insights and consequences for antenatal and postnatal care. Endocrine Reviews. 2001;22:605-630.

49. Stuckey BGA, Kent GN, Allen JR. The biochemical and clinical course of postpartum thyroid dysfunction: the treatment decision. Clin Endocrinol (Oxf). 2001;54:377-383.

50. Haddow JE, Palomaki GE, Allan WC, Williams JR, Knight GJ, Gagnon J, et al. Maternal thyoid deficiency during pregnancy and subsequent neuropsychological development of the child. N Eng J Med. 1999;341:549-555.

51. Nikfar S, Koren G. Managing hypothyroidism during pregnancy. Can Fam Physician. 2001;47:1555-1556.

52. Phoojaroenchanachai M, Sriussadaporn S, Peerapatdit T, Vannassaeng S, Nitiyanant W, Boonnamsiri V, Vichayanrat A. Effect of maternal hyperthyroidism during late pregnancy on the risk of neonatal low birth weight. Clin Endocrinol (Ox). 2001;54:365-370.

53. Hendrick V, Altshsuler LL, Whvbrow P. Psychoendocrinology of mood disorders: the hypothalamic-pituitary-thyroid axis. Psychiatr Clin North Am. 1998;21:277-292.

54. Mallett P, Andrew M, Hunter C, Smith J, Richards C, Othman S, et al. Cognitive function, thyroid status and postpartum depression. Acta Psychiatr Scand. 1995;91:243-246.

55. Kupperman HS, Wetchler BB, Blatt MHG. Contemporary therapy of the menopausal syndrome. Journal of the American Medical Association. 1959;171:1627-1637.

56. Thompson B, Hart SA, Durno D. Menospausal age and symptomatology in a general practice. J Biosoc Sci. 1973;5:71-82.

57. McKinlay SM, Jefferys M. The menopausal syndrome. British Journal of Preventive and Social Medicine. 1974;28:108-115.

58. Wood C. Menopausal myths. Med J Aust. 1979;1:496-499.

59. Ballingeer CB, Browning MCK, Smith AHW. Hormone
profiles and psychological symptoms in peri-menopausal women. Maturitas. 1987;9:235-251.

60. Coppen A, Whybrow PC, Noguera R, Maggs R, Prange Al. The comparative antidepressant value of L-tryptophan and imipramine with and without attempted potentiation by liothyronine. Arch Gen Psychiatry. 1972;26:234-241.

61. Wheatley D. Potentiation of amitryptilene by thyroid hormone. Arch Gen Psychiatry. 1972;26:229-233.

62. Feighner JP, King LJ, Schukit MA, Croughan HJ, Briscoe W. Hormonal potentiation of imipramine and ECT in primary depression. Am J Psychiatry. 1972;26:234-241.

63. Prange AJ, Wilson IC, Rabon AM, Lipton MA. Enhancement of imipramine antidepressant activity by thyroid hormone. Ain J Psychiatry. 1969;126:39-51.

64. Wilson IC, Prange AJ, McClane TK, Rabon AM, Lipton M. Thyroid hormone enhancement in nonretarded depressions. N Eng J Med. 1970;282:1063-1067.

65. Wilson IC, Prange AJ, Lara PP. L-triiodothyronine alone and with imipramine in the treatment of depressed women. In: Prange AJ, ed. The Thyroid Axis, Drugs and Behavior. New York: Raven Press; 1974:49-62.

66. Altshuler LL, Bauer M, Gitlin MJ, Mintz J, Szuba MP, Leight KL, et al. Does thyroid supplementation accelerate tricyclic antidepressant response? A review and meta-analysis of the literature. Am J Psychiatry. 2001;158:1617-1622.

67. Goodwin FK, Prange AJ Jr, Post RM, Muscettola G, Lipton MA. Potentiation of antidepressant effects by L-triiodothyronine in tricylcic nonresponders. Am J Psychiatry. 1982;139:34-38.

68. Joffe RT. Triiodthyronine (T3) and lithium potentiation of tricyclic antidepressants. Am J Psychiatry. 1988;145:1317-1318.

69. Joffe RT, Singer W. A comparison of triiodothyronine and thyroxine in the potentiation of tricyclic antidepressants. Psychiatry Research. 1990;32:241-252.

70. Aronson R, Offman HJ, Joffe RT, Naylor CD. Tri-iodothyronine augmentation in the treatment of refractory depression: a meta-analysis. Arch Gen Psychiatry. 1996;53:842-848.