[Wise Young]

Prolactin & Spinal Cord Injury

Prolactin is a pituitary hormone. In women, it stimulates the breasts to enlarge and produce milk. It is also said to produce feelings of sexual gratification after intercourse, by repressing the effects of dopamine that causes sexual arousal. It is believed to be responsible for the male's refractory period. High levels of prolactin can cause impotence and loss of libido, a condition called hyperprolactinemia. Prolactin levels increase during ovulation, pregnancy, during breast feeding, and intercourse.

Prolactin is a polypeptide with 199 amino acids (24 kD) and the molecule can be variously glycosylated, phosphorylated, sulfated, as well as fragmented, after release from the pituitary. The transcription factor that stimulates prolactin production is Pit-1 and it is regulated by estrogens that enhance prolactin production and suppress dopamine effects. High prolactin levels suppresses ovulation by inhibiting FSH and GnRH secretion. Prolactin has been implicated in surfactant synthesis in fetal lungs at the end of pregnancy and also immune tolerance of the fetus by the mother during pregnancy (Source).

In women with spinal cord injury, hyperprolactinemia (high prolactin blood levels) is associated with galactorrhea (breast secretions) and amenorrhea (abnormal low or absent menstrual flows). Berezin, et al. (1989) in Israel, described six women who developed hyperprolactinemia, amenorrhea, and galactorrhea after spinal cord injury. Two were postpartum and one was pregnant at the time of injury. One had transient diabetes insipidus. Treatment of bromocriptine reduced the prolactin levels and restored ovulatory cycles. The authors suggested that being pregnant or early postpartum can predispose women with spinal cord injury to have this problem. Yarkony, et al., (1992) likewise reported galactorrhea in four women with SCI. In fact, the inhibitory effect of breast-feeding on fertility is attributed to breast-feeding elevation of prolactin causing amenorrhea during the first 6 months after delivery.

In men, prolactin levels may be higher than normal during the first 3 months after injury and returned to normal thereafter in one early study (Cortes-Gallegos, et al., 1982). Campangolo, et al. (1999) reported no difference of prolactin levels between subjects with spinal cord injury and control subjects. However, in tetraplegic subjects, prolactin correlated highly with dehydroepiandrosterone sulfate levels, suggesting that low prolactin levels is associated with hypogonadism (low testosterone levels) in males. However, high prolactin levels are also associated with hypogonadism and erectile dysfunction in men. Elevated prolactin levels are also associated with abnormally low parathyroid hormone in men with spinal cord injury, compared to those with traumatic brain injury (Mechanick, et al., 1997). High prolactin levels probably the cause gynecomastia (excessive development of the mammary gland) that can occur in men during the first 6 months after spinal cord injury (Heruti, et al., 1997).

Huang, et al. (1998) examined the hypothalamic-pituitary-adrenal axis in 25 men with spinal cord injury. Compared against age-matched male non-injured volunteers, they found 3 of the 25 men had hyperprolactinemia, 3 had elevated basal follicle-stimulating hormone levels, one had elevated basal luteinizing hormone levels, and four had low testosterone levels. In general, the men had lower ACTH response to CRF stimulation, suggesting depressed pituitary response. Eleven of the spinal-injured subjects had abnormally low cortisol response to insulin-induced hypoglycemia. These findings suggest that many men with spinal cord injury have altered hypothalamic-pituitary-adrenal axes. Similarly, three of 16 women with spinal cord injury had elevated prolactin levels. Over 81% of women with SCI had at least one axis abnormality of their hypothalamus-pituitary-ovary-thyroid axis.

Many drugs increase prolactin levels, including anti-psychotic medications. Such drugs include chlorpromazine, haloperidol, clozapine, and others. Excessive thyrotropin-releasing hormone (TRH) can also elevate prolactin levels. Of course, breast feeding elevate prolactin levels. Of course, pituitary tumors can cause very high levels of prolactin and is treated with bromocryptine. Hypothyroidism is associated with hyperprolactinemia and treatment of the hypothyroid condition may resolve the increased prolactin. Interestingly, surgical scars on the chest all and other chest wall irritation (shingles for example) can trigger excessive prolactin secretion. Certain tranquilizers, high blood pressure medications, and anti-nausea medication can lead to excessive prolactin secretion. Oral contraceptives and marijuana may also cause mild prolactin excess (ASRM Fact Sheet: Prolactin Excess (PDF)).

In summary, this is not a hormone that one wants to take if one doesn't have low prolactin levels. It has many side-effects and is not innocuous. Hyperprolactinemia is associated with infertility and impotence, as well as other undesirable side-effects, such as gynecomastia. Given that many people with spinal cord injury have had high prolactin levels (due to medication or other causes) and there is no report of improved recovery, prolactin probably does not promotes neurological recovery. I was unable to find any animal study that suggested beneficial effects of prolactin on spinal cord injury or recovery.

References

1. Berezin M, Ohry A, Shemesh Y, Zeilig G and Brooks ME (1989). Hyperprolactinemia, galactorrhea and amenorrhea in women with a spinal cord injury. Gynecol Endocrinol 3: 159-63. Six women with a traumatic spinal cord injury (SCI) developed hyperprolactinemia, amenorrhea and galactorrhea. Five of them had thoracic level lesions and 1 had a lumbosacral lesion. Two were postpartum and 1 was pregnant at the time of injury. Transient diabetes insipidus developed in 1 patient. Temporary administration of bromocriptine decreased prolactin levels, caused cessation of lactation and restored ovulatory cycles. The syndrome disappeared spontaneously in all 6 patients. Pituitary stalk concussion resulting from the trauma might cause this phenomenon, with the level of the cord injury playing a role. Being pregnant or early postpartum can predispose women to develop this syndrome. Institute of Endocrinology, Chaim Sheba Medical Center, Tel-Hashomer, Israel. http://www.ncbi.nlm.nih.gov/entrez/q...t_uids=2510463
2. Campagnolo DI, Bartlett JA, Chatterton R, Jr. and Keller SE (1999). Adrenal and pituitary hormone patterns after spinal cord injury. Am J Phys Med Rehabil 78: 361-6. Current evidence indicates that the neuroendocrine system is the highest regulator of immune/inflammatory reactions. We hypothesized that immune alterations, which were related to the level of injury, found in a cohort of spinal cord-injured subjects may be influenced by altered hormonal patterns postinjury. Therefore, we investigated aspects of both pituitary and adrenal function in the same cohort of spinal cord-injured subjects. We found significant elevations in both cortisol and dehydroepiandrosterone sulfate in chronic spinal cord-injured survivors compared with their able-bodied age- and gender-matched controls. Levels of dehydroepiandrosterone, adrenocorticotropin, and prolactin were not different in spinal cord-injured subjects overall compared with their controls. Both dehydroepiandrosterone sulfate and dehydroepiandrosterone were higher in tetraplegics compared with their controls, but we found no such differences in paraplegics compared with their controls. When the two groups of spinal cord-injured subjects were compared with each other, we also found differences between these two subject groups in dehydroepiandrosterone sulfate and dehydroepiandrosterone (higher in the tetraplegics compared with paraplegics). We found no differences between either group of spinal cord-injured subjects and their controls for adrenocorticotropin, prolactin, or cortisol. These data suggest that some hormonal differences between subjects and their controls may be further related to the level of injury (specifically dehydroepiandrosterone and dehydroepiandrosterone). Finally, we investigated correlations within subjects for the above hormones. Dehydroepiandrosterone sulfate and prolactin were highly correlated (the higher the dehydroepiandrosterone sulfate, the higher the prolactin) but only in the tetraplegic subjects. Department of Physical Medicine and Rehabilitation, UMDNJ-New Jersey Medical School, Newark, New Jersey 07103-2406, USA. http://www.ncbi.nlm.nih.gov/entrez/q..._uids=10418843
3. Cortes-Gallegos V, Castaneda G, Alonso R, Arellano H, Cervantes C and Parra A (1982). Diurnal variations of pituitary and testicular hormones in paraplegic men. Arch Androl 8: 221-6. The effect of the neuro-spinal cord injury upon testicular physiology was evaluated in six adult paraplegic (PPG) men by measuring the circulating levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), androstenedione, testosterone, and dihydrotestosterone every 4 hr throughout a 24-hr period. Three PPG men were studied within the first 3 months (acute period) and the other three patients 39-79 months (stabilized period) after trauma. Hormonal values were compared with eight age-matched normal adult males. Plasma FSH and LH were constantly above normal concentrations regardless of the sampling time and period of observation, whereas prolactin was higher than normal only during the first two months after trauma, returning to normal afterwards. Plasma androgens were consistently below normal during the first 3 months after injury, and returned toward normal thereafter. There may be a direct relationship between the time elapsed after the spinal cord injury and the plasma androgens concentrations. A possible role of PRL in testicular steroidogenesis is suggested. http://www.ncbi.nlm.nih.gov/entrez/q...t_uids=6808942
4. Heruti RJ, Dankner R, Berezin M, Zeilig G and Ohry A (1997). Gynecomastia following spinal cord disorder. Arch Phys Med Rehabil 78: 534-7. Gynecomastia, an excessive development of the mammary glands in men, is a known phenomenon among patients with spinal cord disorder, yet in the last 50 years it has not been fully described in relation to spinal cord disorder. Over a period of 2 years, six patients with spinal cord disorder (4 secondary to a traumatic injury, 1 to decompression sickness, and 1 to transverse myelitis) manifested gynecomastia. The onset of gynecomastia occurred between 1 to 6 months after injury. These patients are presented along with a review of the possible causes for gynecomastia and a suggested workup routine. A clinical examination for the presence of gynecomastia should be performed for every patient with spinal cord disorder and a thorough endocrinological workup should follow to rule out malignancy and reassure the anxious patient undergoing a disruption of his body image. Department of Neurologic Rehabilitation, Sheba Medical Center, Tel-Hashomer, Israel. http://www.ncbi.nlm.nih.gov/entrez/q...t_uids=9161376
5. Huang TS, Wang YH, Lai JS, Chang CC and Lien IN (1996). The hypothalamus-pituitary-ovary and hypothalamus-pituitary-thyroid axes in spinal cord-injured women. Metabolism 45: 718-22. Sixteen women with spinal cord injury (SCI) underwent studies of the hypothalamus-pituitary-ovary (HPO) and hypothalamus-pituitary-thyroid (HPT) axes with luteinizing hormone (LH) releasing hormone (LHRH) and thyrotropin (TSH) releasing hormone (TRH) stimulation tests during the early follicular phase. The mean interval from injury to participation in this study was 7.5 years (range, 1.5 to 13.1). All subjects were menstruating regularly. Five (35.7%) SCI subjects who were menstruating before injury had postinjury amenorrhea for 1 to 12 months, and the other nine (64.3%) SCI subjects had no interruption of menstruation after injury. Two SCI subjects whose injury occurred in preadolescence proceeded to menarche without any delay. The amount of menstrual flow was noted to be reduced in nine (64.3%) SCI subjects. Two and three SCI subjects had elevated follicle-stimulating hormone (FSH) and prolactin (PRL) levels, respectively. LH responses to LHRH were significantly higher in the SCI group (P < .001). Ten (62.6%) SCI subjects had enhanced LH responses to LHRH. The mean TSH, PRL, and FSH responses to TRH and LHRH of the SCI group were not significantly different from those of age-matched controls. However, five (31.2%), four (25.0%), and five (31.2%) SCI subjects had enhanced TSH, PRL, and FSH responses to TRH and LHRH, respectively. Six (37.5%) SCI subjects had a delayed FSH response to LHRH. In total, 13 (81.2%) SCI subjects had at least one axis abnormality. These findings are consistent with the hypothesis that changes of central neurotransmitters may occur after SCI. Department of Medicine, National Taiwan University Hospital, Taipei, Republic of China. http://www.ncbi.nlm.nih.gov/entrez/q...t_uids=8637446
6. Huang TS, Wang YH, Lee SH and Lai JS (1998). Impaired hypothalamus-pituitary-adrenal axis in men with spinal cord injuries. Am J Phys Med Rehabil 77: 108-12. Twenty-five men with spinal cord injuries were studied for evaluation of the hypothalamus-pituitary-adrenal axis, using corticotropin-releasing hormone and insulin-induced hypoglycemia. Twenty-five age-matched healthy male volunteers served as controls. Three spinal cord-injured subjects had hyperprolactinemia, three had elevated basal follicle-stimulating hormone levels, one had an elevated basal luteinizing hormone level, and four had hypotestosteronemia. The mean plasma adrenocorticotropin response to corticotropin-releasing hormone of spinal cord-injured subjects was smaller than that of the healthy controls but did not reach a statistical significance. The cortisol response to corticotropin-releasing hormone of the spinal cord-injured subjects was significantly lower than that of healthy controls. However, the difference disappeared if a correction was made for baseline values. Six spinal cord-injured subjects did not have a cortisol response to insulin-induced hypoglycemia, and they had either a minimal or no adrenocorticotropin response. Another 11 spinal cord-injured subjects had a maximal cortisol response to insulin-induced hypoglycemia below the lowest limit of normal, i.e., 0.5 micromol/l. Among these spinal cord-injured subjects, three had a less than 50% increase of plasma adrenocorticotropin after insulin-induced hypoglycemia. These findings are consistent with the notion that spinal cord-injured subjects have an altered central neurotransmitter tone and substantiate the hypothesis that an afferent neural pathway exists between the adrenal and hypothalamus and may modulate stress-induced secretion of adrenocorticotropin. Long-term abnormal adrenocorticotropin secretion may cause mild adrenocortical atrophy and, thereby, a reduced cortisol response. Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Republic of China. http://www.ncbi.nlm.nih.gov/entrez/q...t_uids=9558010
7. Mechanick JI, Pomerantz F, Flanagan S, Stein A, Gordon WA and Ragnarsson KT (1997). Parathyroid hormone suppression in spinal cord injury patients is associated with the degree of neurologic impairment and not the level of injury. Arch Phys Med Rehabil 78: 692-6. OBJECTIVE: To demonstrate that after spinal cord injury (SCI) suppression of the parathyroid-vitamin D axis is associated with the degree of neurologic impairment and not the level of injury. DESIGN: A retrospective analysis of clinical and biochemical data obtained from hospital records of patients with SCI compared to a control group of patients with traumatic brain injury (TBI). SETTING: The inpatient rehabilitation unit of a tertiary care hospital. SUBJECTS: The medical records of 82 consecutive admissions to the rehabilitation unit with a diagnosis of SCI or TBI were reviewed. Patients with SCI were classified by the American Spinal Injury Association (ASIA) impairment scale and then grouped based on the completeness and level of injury. MAIN OUTCOME MEASURE: Comparisons of serum parathyroid hormone (PTH), 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D (1,25-D) were planned. Multiple comparisons were performed for total and ionized serum calcium levels, serum phosphorus levels, and 24-hour urinary calcium excretion rates to reflect changes in mineral homeostasis. Multiple comparisons were also performed for serum albumin, prolactin, thyroid function tests, and AM cortisol levels, as well as 24-hour urinary urea nitrogen and cortisol excretion rates to reflect metabolic responses to stress. RESULTS: Patients with SCI had significant suppression in PTH (p < .000009) and 1,25-D (p < .02) levels with elevated phosphorus (p < 0.03) and prolactin (p < .03) levels compared to patients with TBI. Also, more patients with SCI were hypoalbuminemic (p < .003) than patients with TBI. Patients with complete SCI (ASIA A) had more suppressed PTH (p < .03) and higher urinary urea nitrogen (p < .05) levels than SCI patients with incomplete injuries (ASIA B-D). Patients with complete, but not incomplete, SCI had lower albumin levels than patients with TBI (p < .05). These differences were not found between patients with tetraplegic and paraplegic SCI. ASIA motor scores did not correlate with any of the measured parameters but when used as a covariate did abolish differences in PTH and 1,25-D among the study groups by ANOVA. CONCLUSION: In patients with SCI, the degree of neurologic impairment, and not the level of injury, is associated with PTH suppression and markers of metabolic stress. Division of Endocrinology and Metabolism, Mount Sinai School of Medicine, New York, NY 10029, USA. http://www.ncbi.nlm.nih.gov/entrez/q...t_uids=9228870
8. Wheeler GD, Ashley EA, Harber V, Laskin JJ, Olenik LM, Sloley D, Burnham R, Steadward RD and Cumming DC (1996). Hormonal responses to graded-resistance, FES-assisted strength training in spinal cord-injured. Spinal Cord 34: 264-7. Functional electrical stimulation (FES) assisted resistance training has been effective in increasing muscular strength and endurance in spinal cord injured men and women in preparation for FES-assisted cycle programs and for FES-assisted standing and walking. Increases in blood pressure and a concomitant bradycardia suggestive of autonomic dysreflexia have been reported during FES-assisted resistance training. Self-induced autonomic dysreflexia in athletes who use wheelchairs suppressed the normal exercise induced serum testosterone increase. We, therefore, examined the changes in hematocrit and circulating levels of testosterone, sex hormone binding globulin (SHBG), cortisol, prolactin, norepinephrine and epinephrine during FES assisted resistance exercise in five high spinal cord injured men (SCI) and comparable maximal exercise in five able bodied controls (AB). Mean serum testosterone levels significantly increased with FES-assisted resistance training in SCI and maximal resistance exercise in AB with no significant change in hematocrit or SHBG. Prolactin, cortisol and epinephrine levels were unchanged while norepinephrine levels were significantly increased in SCI and AB. These findings suggest that there is no concern over inadequate physiological androgen response to an exercise stimulus in SCI. The data do not support the previous findings that elevated levels of norepinephrine in autonomic dysreflexia suppress testosterone response to exercise. Rick Hansen Centre, University of Alberta, Edmonton, Canada. http://www.ncbi.nlm.nih.gov/entrez/q...t_uids=8963972
9. Yarkony GM, Novick AK, Roth EJ, Kirschner KL, Rayner S and Betts HB (1992). Galactorrhea: a complication of spinal cord injury. Arch Phys Med Rehabil 73: 878-80. Galactorrhea, a secretion of milk or milk-like products from the breast in the absence of parturition, has been reported to occur in women with spinal cord injuries in association with amenorrhea and hyperprolactinemia. Four cases of galactorrhea in association with spinal cord injury are reported. Galactorrhea developed in four spinal cord injured women who had thoracic paraplegia. The onset of galactorrhea was from one month to five months after injury. Although the onset of galactorrhea may have been related to prescribed medications in all four cases, insufficient data exist to draw conclusions. The three women whose galactorrhea persisted declined treatment and galactorrhea continuing for more than two years in one instance. We conclude that galactorrhea with or without amenorrhea may develop after a spinal cord injury and that spinal cord injured women may have an enhanced sensitivity to medication-induced galactorrhea. Department of Rehabilitation Medicine, Northwestern University Medical School, Chicago, IL. http://www.ncbi.nlm.nih.gov/entrez/q...t_uids=1514898