Prolactin Deficiency



In the vast majority of prolactin deficiency states, the deficiency occurs secondary to general anterior pituitary dysfunction. The most commonly associated condition is postpartum pituitary necrosis (Sheehan syndrome); however, prolactin deficiency can also be caused by anterior pituitary impairment secondary to pituitary (or extrapituitary) tumor or treatment of tumor, parasellar diseases, head injury, infection (eg, tuberculosis, histoplasmosis), or infiltrative diseases (eg, sarcoidosis, hemochromatosis, lymphocytic hypophysitis).[1, 2, 3]

Partial isolated prolactin deficiency is rare, and case reports of total isolated prolactin deficiency are rarer still and may have a genetic component (ie, familial puerperal alactogenesis).[4, 5, 6] Although the endocrine and metabolic function of prolactin is not fully understood, the clinical manifestation of prolactin deficiency is probably limited to puerperal alactogenesis.[4]


Prolactin deficiency is characterized by the inability of pituitary lactotrophs to secrete prolactin and by the resulting lack of puerperal lactogenesis. Other pathophysiologic mechanisms have not been fully established. Prolactin is principally regulated by tonic inhibition rather than by intermittent stimulation. Its principal inhibitory regulator is dopamine. Prolactin enhances dopamine secretion and thus exhibits feedback inhibition of its own secretion. The only other known physiologic inhibitors include triiodothyronine (T3) and somatostatin.[7]

Menstrual disorders, delayed puberty, infertility, and subfertility have been associated with hypoprolactinemia, through mechanisms that are not entirely clear. Prolactin concentration in follicular fluid during in vitro fertilization (IVF) correlates with the oocyte maturation level and fertilization rate. Further, in a randomized human trial, bromocriptine-induced hypoprolactinemia during IVF resulted in decreased fertilization and cleavage rate compared with a hyperprolactinemic cycle group. A partial prolactin deficiency may result in inadequate lactation. Further, a possibility exists that male factor infertility may be associated with hypoprolactinemia. Serum prolactin levels that were suppressed by bromocriptine resulted in decreased spermatogenesis and decreased testosterone production in healthy male volunteers.[8]

Some data support the idea that prolactin is also an immunoregulating hormone. Prolactin receptors have been found on human T lymphocytes and B lymphocytes, and some data support T-lymphocyte dependence on prolactin for maintenance of immune competence.[9] In research using a mouse model, inhibition of prolactin release impaired lymphocyte function and depressed macrophage activation.[10] Further, the study's mice had a decreased tolerance for bacterial exposure; this reduced tolerance was manifested by death from a normally nonlethal dose of bacteria.

Part of the immunosuppressive effects of cyclosporine may be mediated through a competitive antagonistic action at the prolactin receptor site. Further evidence is found in the observation of the immunosuppressant effects of bromocriptine, which has been shown to be an effective adjuvant (immunosuppressant) in patients after transplantation and in patients with autoimmune disease.[11, 12]

Because prolactin release is inversely related to dopamine levels in the anterior pituitary, critically ill patients on prolonged dopamine infusion have resultant prolactin deficiency. It has been hypothesized that this causes impairment of the T-lymphocyte proliferation response; this impairment occurs in patients in intensive care units (ICUs) and may be an important cause of infection susceptibility in this group. However, no data support the hypothesis that lack of prolactin in otherwise healthy patients results in immunodeficiency.

Several studies have found a correlation in preterm infants between hypoprolactinemia and increased mortality.[13] The precise pathophysiologic mechanism is unknown, but it is speculated to be associated with the effects of prolactin on surfactant synthesis, whole-body water regulation, or gastrointestinal maturation.[14]



United States

In association with other anterior pituitary dysfunction, prolactin deficiency is uncommon except with pituitary infarction (Sheehan syndrome). In isolation, partial prolactin deficiency occurs rarely, and total isolated prolactin deficiency is limited to case reports.[5, 6]


No fatalities resulting from prolactin deficiency in adults have been documented. In preterm infants, however, increased mortality may be associated with hypoprolactinemia.[13]


No race predilection exists for prolactin deficiency.


Clinical manifestations occur only in females (puerperal alactogenesis). Excluding women with Sheehan syndrome, incidence in males and females is probably equal.


The prevalence of hypoprolactinemia parallels the prevalence of all causes of hypopituitarism. Obviously, Sheehan syndrome is possible only in women of reproductive age.


The most important historical finding in prolactin deficiency is puerperal alactogenesis. A history of anterior pituitary dysfunction is also important.


No specific physical findings are associated with hypoprolactinemia other than puerperal alactogenesis. The most common symptom complex of anterior pituitary dysfunction in men and women is secondary hypogonadism caused by deficiencies of luteinizing hormone (LH) and follicle-stimulating hormone (FSH).


The most common causes of prolactin deficiency include postpartum pituitary necrosis (Sheehan syndrome)[15, 16] and all other causes of anterior pituitary dysfunction.[17]

Laboratory Studies

The prolactin level following administration of thyrotropin may be the best screening test for Sheehan syndrome.

Usually, no workup is necessary, because supplemental prolactin is not yet available for treatment; however, suspicion of the disease can be confirmed by administering thyrotropin-releasing hormone or an antidopaminergic agent (eg, metoclopramide) and measuring prolactin levels. Failure to respond (rise in the level of prolactin) in the setting of the challenge is diagnostic.

The following tests can also be performed: prolactin assay in the third trimester or in peripartum women; LH, FSH, thyrotropin, and free thyroxine; and other tests as necessary to diagnose anterior hypopituitarism.

The author recommends that female patients who are interested in lactation and have suspected anterior pituitary dysfunction have prolactin measured in the third trimester of pregnancy or peripartum. This test can then be used to ascertain the possibility of puerperal alactogenesis. In this way, the patient can be forewarned of her inability to support lactation, and a recommendation for formula and bottle-feeding can be made. This enables the patient to avoid the often traumatic experience of waiting for her milk to come in, with this event instead being predicted by a simple laboratory test. Third trimester prolactin levels in normal pregnancies are often 150-250 mcg/L.

Normal baseline serum prolactin levels are less than 20 mcg/L in nongravid women and are usually less than 10 mcg/L in men. During pregnancy, serum levels may reach 200-500 mcg/L.

Imaging Studies

Consider pituitary imaging if anterior pituitary dysfunction is suspected. Magnetic resonance imaging (MRI) is the usual imaging procedure.

Medical Care

Generally, formula and/or bottle-feeding of infants are recommended for women with puerperal hypoprolactinemia and insufficient milk supply. Drugs to increase milk output generally are not effective.


Consult an endocrinologist.

Medication Summary

Currently, no medication exists to treat prolactin deficiency; however, experimental recombinant human prolactin has been formulated and has been shown to be effective in correcting lactational performance in rats treated with bromocriptine.

Inadequate lactation may respond to antidopaminergic agents that block the dopamine-induced hypothalamic inhibitory control of prolactin. Metoclopramide has been shown in prospective, placebo-controlled studies to significantly increase milk yield in patients with inadequate lactation.[24, 25, 26, 27, 28, 29] Subfertility caused by hypoprolactinemia may be treated with clomiphene citrate (50 mg/d for 5 d) or with gonadotropins (LH, FSH; dose varies).

Metoclopramide (Clopra, Maxolon, Reglan)

Clinical Context:  GI prokinetic agent used for the treatment of diabetic gastroparesis and gastroesophageal reflux, as well as for the prevention of nausea associated with chemotherapy. Metoclopramide has been shown to increase milk yield in patients with inadequate lactation.

Class Summary

These block dopamine-induced inhibitory control of prolactin at the hypothalamic level.

Further Inpatient Care

Typically, prolactin deficiency is not managed in the hospital setting.

Patient Education

If hypoprolactinemia is established, educate the patient about the reality of not being able to breast-feed her baby.

For excellent patient education resources, visit eMedicineHealth's Women's Health Center. Also, see eMedicineHealth's patient education article Breastfeeding.


Charles T Benson, MD, PhD, Medical Fellow, Eli Lilly and Company, UK

Disclosure: Received salary from Eli Lilly & Co for employment.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Yoram Shenker, MD, Chief of Endocrinology Section, Veterans Affairs Medical Center of Madison; Interim Chief, Associate Professor, Department of Internal Medicine, Section of Endocrinology, Diabetes and Metabolism, University of Wisconsin at Madison

Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD, Professor Emeritus of Medicine, St Louis University School of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Frederick H Ziel, MD, Associate Professor of Medicine, University of California, Los Angeles, David Geffen School of Medicine; Physician-In-Charge, Endocrinology/Diabetes Center, Director of Medical Education, Kaiser Permanente Woodland Hills; Chair of Endocrinology, Co-Chair of Diabetes Complete Care Program, Southern California Permanente Medical Group

Disclosure: Nothing to disclose.


  1. Cosman F, Post KD, Holub DA, et al. Lymphocytic hypophysitis. Report of 3 new cases and review of the literature. Medicine (Baltimore). 1989 Jul. 68(4):240-56. [View Abstract]
  2. Thodou E, Asa SL, Kontogeorgos G, et al. Clinical case seminar: lymphocytic hypophysitis: clinicopathological findings. J Clin Endocrinol Metab. 1995 Aug. 80(8):2302-11. [View Abstract]
  3. Toledano Y, Lubetsky A, Shimon I. Acquired prolactin deficiency in patients with disorders of the hypothalamic-pituitary axis. J Endocrinol Invest. 2007 Apr. 30(4):268-73. [View Abstract]
  4. Zargar AH, Masoodi SR, Laway BA, et al. Familial puerperal alactogenesis: possibility of a genetically transmitted isolated prolactin deficiency. Br J Obstet Gynaecol. 1997 May. 104(5):629-31. [View Abstract]
  5. Falk RJ. Isolated prolactin deficiency: a case report. Fertil Steril. 1992 Nov. 58(5):1060-2. [View Abstract]
  6. Kauppila A, Chatelain P, Kirkinen P, et al. Isolated prolactin deficiency in a woman with puerperal alactogenesis. J Clin Endocrinol Metab. 1987 Feb. 64(2):309-12. [View Abstract]
  7. Swaminathan G, Varghese B, Thangavel C, et al. Prolactin stimulates ubiquitination, initial internalization, and degradation of its receptor via catalytic activation of Janus kinase 2. J Endocrinol. 2008 Feb. 196(2):R1-7. [View Abstract]
  8. Oseko F, Nakano A, Morikawa K, et al. Effects of chronic bromocriptine-induced hypoprolactinemia on plasma testosterone responses to human chorionic gonadotropin stimulation in normal men. Fertil Steril. 1991 Feb. 55(2):355-7. [View Abstract]
  9. Russell DH, Kibler R, Matrisian L, et al. Prolactin receptors on human T and B lymphocytes: antagonism of prolactin binding by cyclosporine. J Immunol. 1985 May. 134(5):3027-31. [View Abstract]
  10. Bernton EW, Meltzer MS, Holaday JW. Suppression of macrophage activation and T-lymphocyte function in hypoprolactinemic mice. Science. 1988 Jan 22. 239(4838):401-4. [View Abstract]
  11. Carrier M, Wild J, Pelletier LC, et al. Bromocriptine as an adjuvant to cyclosporine immunosuppression after heart transplantation. Ann Thorac Surg. 1990 Jan. 49(1):129-32. [View Abstract]
  12. Palestine AG, Nussenblatt RB, Gelato M. Therapy for human autoimmune uveitis with low-dose cyclosporine plus bromocriptine. Transplant Proc. 1988 Jun. 20(3 Suppl 4):131-5. [View Abstract]
  13. Lucas A, Baker BA, Cole TJ. Plasma prolactin and clinical outcome in preterm infants. Arch Dis Child. 1990 Sep. 65(9):977-83. [View Abstract]
  14. Bonomo IT, Lisboa PC, Pereira AR, et al. Prolactin inhibition in dams during lactation programs for overweight and leptin resistance in adult offspring. J Endocrinol. 2007 Feb. 192(2):339-44. [View Abstract]
  15. Laway BA, Mir SA, Gojwari T, Shah TR, Zargar AH. Selective preservation of anterior pituitary functions in patients with Sheehan's syndrome. Indian J Endocrinol Metab. 2011 Sep. 15 Suppl 3:S238-41. [View Abstract]
  16. Shivaprasad C. Sheehan's syndrome: Newer advances. Indian J Endocrinol Metab. 2011 Sep. 15 Suppl 3:S203-7. [View Abstract]
  17. Leng L, Zhang Y. Effects of an estrogen receptor antagonist on proliferation, prolactin secretion and growth factor expression in the MMQ pituitary prolactinoma cell line. J Clin Neurosci. 2011 Oct 18. [View Abstract]
  18. Fofanova O, Takamura N, Kinoshita E, et al. Compound heterozygous deletion of the PROP-1 gene in children with combined pituitary hormone deficiency. J Clin Endocrinol Metab. 1998 Jul. 83(7):2601-4. [View Abstract]
  19. Rosenbloom AL, Almonte AS, Brown MR, et al. Clinical and biochemical phenotype of familial anterior hypopituitarism from mutation of the PROP1 gene. J Clin Endocrinol Metab. 1999 Jan. 84(1):50-7. [View Abstract]
  20. Yang H, Dixit VD, Patel K, et al. Reduction in hypophyseal growth hormone and prolactin expression due to deficiency in ghrelin receptor signaling is associated with Pit-1 suppression: relevance to the immune system. Brain Behav Immun. 2008 Jun 17. [View Abstract]
  21. Samuels MH, Henry P, Kleinschmidt-Demasters B, et al. Pulsatile prolactin secretion in hyperprolactinemia due to presumed pituitary stalk interruption. J Clin Endocrinol Metab. 1991 Dec. 73(6):1289-93. [View Abstract]
  22. Diaz S, Seron-Ferre M, Cardenas H, et al. Circadian variation of basal plasma prolactin, prolactin response to suckling, and length of amenorrhea in nursing women. J Clin Endocrinol Metab. 1989 May. 68(5):946-55. [View Abstract]
  23. Stawerska R, Lewinski A, Smyczynska J, et al. Circadian pattern of prolactin secretion in children with growth hormone deficiency and congenital organic lesions in the hypothalamic-pituitary region. Neuro Endocrinol Lett. 2007 Dec. 28(6):765-74. [View Abstract]
  24. Ehrenkranz RA, Ackerman BA. Metoclopramide effect on faltering milk production by mothers of premature infants. Pediatrics. 1986 Oct. 78(4):614-20. [View Abstract]
  25. Gupta AP, Gupta PK. Metoclopramide as a lactogogue. Clin Pediatr (Phila). 1985 May. 24(5):269-72. [View Abstract]
  26. Kauppila A, Anunti P, Kivinen S, et al. Metoclopramide and breast feeding: efficacy and anterior pituitary responses of the mother and the child. Eur J Obstet Gynecol Reprod Biol. 1985 Jan. 19(1):19-22. [View Abstract]
  27. Kauppila A, Kivinen S, Ylikorkala O. A dose response relation between improved lactation and metoclopramide. Lancet. 1981 May 30. 1(8231):1175-7. [View Abstract]
  28. Kauppila A, Kivinen S, Ylikorkala O. Metoclopramide increases prolactin release and milk secretion in puerperium without stimulating the secretion of thyrotropin and thyroid hormones. J Clin Endocrinol Metab. 1981 Mar. 52(3):436-9. [View Abstract]
  29. Sousa PL. Letter: Metoclopramide and breast-feeding. Br Med J. 1975 Mar 1. 1(5956):512. [View Abstract]
  30. Andersen AN, Lund-Andersen C, Larsen JF, et al. Suppressed prolactin but normal neurophysin levels in cigarette smoking breast-feeding women. Clin Endocrinol (Oxf). 1982 Oct. 17(4):363-8. [View Abstract]
  31. Carlson HE, Brickman AS, Bottazzo GF. Prolactin deficiency in pseudohypoparathyroidism. N Engl J Med. 1977 Jan 20. 296(3):140-4. [View Abstract]
  32. Clevenger CV, Altmann SW, Prystowsky MB. Requirement of nuclear prolactin for interleukin-2--stimulated proliferation of T lymphocytes. Science. 1991 Jul 5. 253(5015):77-9. [View Abstract]
  33. Devins SS, Miller A, Herndon BL, et al. Effects of dopamine on T-lymphocyte proliferative responses and serum prolactin concentrations in critically ill patients. Crit Care Med. 1992 Dec. 20(12):1644-9. [View Abstract]
  34. Doty RL, Fernandez AD, Levine MA, et al. Olfactory dysfunction in type I pseudohypoparathyroidism: dissociation from Gs alpha protein deficiency. J Clin Endocrinol Metab. 1997 Jan. 82(1):247-50. [View Abstract]
  35. Du Ruisseau P, Taché Y, Brazeau P, et al. Effects of chronic immobilization stress on pituitary hormone secretion, on hypothalamic factor levels, and on pituitary responsiveness to LHRH and TRH in female rats. Neuroendocrinology. 1979. 29(2):90-9. [View Abstract]
  36. Gonzales GF, Velasquez G, Garcia-Hjarles M. Hypoprolactinemia as related to seminal quality and serum testosterone. Arch Androl. 1989. 23(3):259-65. [View Abstract]
  37. Hypoprolactinaemia. Lancet. 1987 Jun 13. 1(8546):1356-7. [View Abstract]
  38. Kauppila A. Isolated prolactin deficiency. Curr Ther Endocrinol Metab. 1997. 6:31-3. [View Abstract]
  39. Lopez-Calderon A, Ariznavarreta C, Calderon MD, et al. Role of the adrenal cortex in chronic stress-induced inhibition of prolactin secretion in male rats. J Endocrinol. 1989 Feb. 120(2):269-73. [View Abstract]
  40. Mukherjee A, Murray RD, Columb B, Gleeson HK, Shalet SM. Acquired prolactin deficiency indicates severe hypopituitarism in patients with disease of the hypothalamic-pituitary axis. Clin Endocrinol (Oxf). 2003 Dec. 59(6):743-8. [View Abstract]
  41. Murphy WJ, Rui H, Longo DL. Effects of growth hormone and prolactin immune development and function. Life Sci. 1995. 57(1):1-14. [View Abstract]
  42. Oda T, Yoshimura Y, Takehara Y, et al. Effects of prolactin on fertilization and cleavage of human oocytes. Horm Res. 1991. 35 Suppl 1:33-8. [View Abstract]
  43. Ozbey N, Inanc S, Aral F, et al. Clinical and laboratory evaluation of 40 patients with Sheehan's syndrome. Isr J Med Sci. 1994 Nov. 30(11):826-9. [View Abstract]
  44. Parks JS, Abdul-Latif H, Kinoshita E, et al. Genetics of growth hormone gene expression. Horm Res. 1993. 40(1-3):54-61. [View Abstract]
  45. Peters F, Schulze-Tollert J, Schuth W. Thyrotrophin-releasing hormone--a lactation-promoting agent?. Br J Obstet Gynaecol. 1991 Sep. 98(9):880-5. [View Abstract]
  46. Poindexter AN, Buttram VC, Besch PK, et al. Circulating prolactin levels. I. Normal females. Int J Fertil. 1977. 22(1):1-5. [View Abstract]
  47. Pullano JG, Cohen-Addad N, Apuzzio JJ, et al. Water and salt conservation in the human fetus and newborn. I. Evidence for a role of fetal prolactin. J Clin Endocrinol Metab. 1989 Dec. 69(6):1180-6. [View Abstract]
  48. Rigg LA, Lein A, Yen SS. Pattern of increase in circulating prolactin levels during human gestation. Am J Obstet Gynecol. 1977 Oct 15. 129(4):454-6. [View Abstract]
  49. Russell DH. New aspects of prolactin and immunity: a lymphocyte-derived prolactin-like product and nuclear protein kinase C activation. Trends Pharmacol Sci. 1989 Jan. 10(1):40-4. [View Abstract]
  50. Russell DH, Larson DF, Cardon SB, et al. Cyclosporine inhibits prolactin induction of ornithine decarboxylase in rat tissues. Mol Cell Endocrinol. 1984 May. 35(2-3):159-66. [View Abstract]
  51. Seibel MM, Smith D, Dlugi AM, et al. Periovulatory follicular fluid hormone levels in spontaneous human cycles. J Clin Endocrinol Metab. 1989 Jun. 68(6):1073-7. [View Abstract]
  52. Sheehan HL. The recognition of chronic hypopituitarism resulting from postpartum pituitary necrosis. Am J Obstet Gynecol. 1971 Nov. 111(6):852-4. [View Abstract]
  53. Tucker HA. Endocrinology of lactation. Semin Perinatol. 1979 Jul. 3(3):199-223. [View Abstract]
  54. Turkington RW. Phenothiazine stimulation test for prolactin reserve: the syndrome of isolated prolactin deficiency. J Clin Endocrinol Metab. 1972 Jan. 34(1):246-9. [View Abstract]
  55. Tyson JE, Perez A, Zanartu J. Human lactational response to oral thyrotropin releasing hormone. J Clin Endocrinol Metab. 1976 Oct. 43(4):760-8. [View Abstract]
  56. Weinstein LS, Liu J, Sakamoto A, et al. Minireview: GNAS: normal and abnormal functions. Endocrinology. 2004 Dec. 145(12):5459-64. [View Abstract]
  57. Wettschureck N, Offermanns S. Mammalian G proteins and their cell type specific functions. Physiol Rev. 2005 Oct. 85(4):1159-204. [View Abstract]
  58. Yazigi RA, Quintero CH, Salameh WA. Prolactin disorders. Fertil Steril. 1997 Feb. 67(2):215-25. [View Abstract]
  59. Ylikorkala O, Kivinen S, Kauppila A. Oral administration of TRH in puerperal women: effect on insufficient lactation, thyroid hormones and on the responses of TSH and prolactin to intravenous TRH. Acta Endocrinol (Copenh). 1980 Apr. 93(4):413-8. [View Abstract]
  60. Yoneda N, Irahara M, Saito S, et al. Usefulness of recombinant human prolactin for treatment of poor puerperal lactation in a rat model. Eur J Endocrinol. 1995 Nov. 133(5):613-7. [View Abstract]