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Galactorrhea: a complication of spinal cord injury.

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.

Adult

Galactorrhea and pituitary tumors in postpill and non-postpill secondary amenorrhea.

One hundred sixty-seven women with secondary amenorrhea were observed from six months to four years. In 66 patients, the amenorrhea followed the discontinuation of oral contraceptives (postpill) while in the remaining 101 the amenorrhea was not temporally pill related (non-postpill). Galactorrhea was present in 43 (65%) of those with postpill amenorrhea and in 32 (32%) of those with non-postpill amenorrhea (p less than 0.001). Tomography of the sella turcica was performed in the 75 women with galactorrhea and in the 35 without galactorrhea who did not have withdrawal uterine bleeding following progesterone administration and who had low or normal serum follicle-stimulating hormone levels (hypothalamic-pituitary failure). Forty of the 75 patients with amenorrhea and galactorrhea had radiographic evidence of a pituitary tumor whereas only eight of 35 patients with hypothalamic-pituitary failure without galactorrhea had an abnormal sella turcica (p less than 0.01). The incidence of radiographic abnormalities in those with galactorrhea was similar in both the postpill and non-postpill groups.

Adolescent

Treatment of women with the galactorrhea-amenorrhea syndrome with pyridoxine (vitamin B6).

Three women with the galactorrhea-amenorrhea syndrome and elevated prolactin concentrations experienced a return of regular ovulatory menses within 37-94 days after starting pyridoxine treatment (200-600 mg/day). In each the galactorrhea ceased and serum prolactin levels were maintained in the normal range while taking pyridoxine. In two other women with prolonged secondary amenorrhea but without hyperprolactinemia or galactorrhea, pyridoxine at dosages up to 600 mg/day did not restore ovulatory menses. Pyridoxine treatment was also ineffective in decreasing profuse galactorrhea in one woman with normal prolactin levels and regular ovulatory menses. In the three women effectively treated with pyridoxine, the galactorrhea returned, serum prolactin levels increased, and the menses ceased after discontinuing pyridoxine. These results imply that pyridoxine, by decreasing the excessive secretion of prolactin, may be useful in the long-term medical management of women with hyperprolactinemia and the galactorrhea-amenorrhea syndrome.

Adult

Treatment of galactorrhea-amenorrhea syndrome with 2-Br-alpha-ergocryptin (CB 154). Clinical response and pattern of pituitary and steriod hormones before and during therapy.

2 Bromo-alpha-ergocryptine, a specific prolactin inhibitor, was administered to 9 patients suffering from galactorrhea-amenorrhea syndrome of varying aetiology. Plasma levels of FSH, LH, prolactin, total estrogens and progesterone were measured by radioimmunoassy before and after treatment initiation. Prior to treatment, plasma prolactin levels were in all cases supraphysiological. FSH and LH levels were, with the exception of one patient, in the low cyclic range. One patient had subnormal gonadotropin levels, presumably reflecting hypophyseal insufficiency following surgical removal of a pituitary adenoma. Mean plasma levels of total estrogens were in the lower normal range. Administration of CB 154 led in all cases to a reduction of plasma prolactin levels. In eight cases, galactorrhea was suppressed during the first month of treatment. Eight patients menstruated and seven ovulated as indicated by the basal body temperature (BBT) or plasma progesterone measurement. The postoperative hypophyseal tumor patient did not, with the exception of galactorrhea suppression, respond to treatment, presumably due to hypophyseal insufficiency. 2 patients conceived during the course of treatment. One patient, who developed galactorrhea-amenorrhea syndrome as a result of psychopharmacological drug administration received 7,5 mg/day CB 154. Prolactin secretion, as indicated by plasma levels, was inhibited but the inhibitation was much slower in onset than that exhibited by the other patients and this patient ovulated only after 5 months of treatment. Upon withdrawal of CB 154 therapy after 6 to 7 months, the patients redeveloped galactorrhea-amenorrhea syndrome, so that a definitive cure could not be demonstrated.

Adult

Ineffectiveness of pyridoxine (B6) to alter secretion of growth hormone and prolactin and absence of therapeutic effects on galactorrhea-amenorrhea syndromes.

The acute effect of pyridoxine (B6) on serum GH and PRL levels and its chronic effects on galactorrhea in nine subjects (group I, n=4, idiopathic galactorrhea with normal PRL levels and normal menses; Group II, n=5, galactorrhea-amenorrhea with increased PRL levels) have been studied. Pyridoxine did not acutely alter GH or PRL levels. There was no decrease in galactorrhea, no resumption of menses and no decrease in PRL following tow months of B6 therapy. In contrast, bromocriptine was effective in suppressing galactorrhea and restoring normal menses in group II subjects and remains the therapy of choice for this purpose.

Amenorrhea

Clinical and endocrinological analyses of patients with galactorrhea and menstrual disorders due to sulpiride or metoclopramide.

The clinical courses of galactorrhea and menstrual disorders were studied in 18 women with galactorrhea induced by sulpiride (SLP) or metoclopramide (MCP) given for the treatment of gastrointestinal diseases. The response of PRL and TSH to 500 micrograms iv TRH and the response of LH and FSH to 100 micrograms LRH were assessed by retrospective analysis during treatment in nine patients (six, SLP; three, MCP) and shortly after the end of treatment in nine patients (seven, SLP; two, MCP). The average time from the initiation of treatment to the onset of galactorrhea was 27.2 +/- 4.7 (mean +/- SE) days in the 13 SLP-treated patients and 23.2 +/- 5.8 days in the 5 MCP-treated patients. Five of the SLP-treated patients experienced amenorrhea, four had oligomenorrhea, and one had dysfunctional bleeding. In the MCP-treated patients, oligomenorrhea and dysfunctional bleeding occurred in one each. The average length of time from the end of treatment to disappearance of galactorrhea was 50.0 +/- 7.3 days in the SLP-treated patients and 56.6 +/- 12.1 days in the MCP-treated patients. Cyclic uterine bleeding returned within 2 months after treatment was stopped. Elevated PRL levels with good response to TRH were observed in four of six patients during SLP treatment, and in two of three patients during MCP treatment. Basal PRL levels and response to TRH were normal in almost all patients after the drugs were withdrawn. Normal HL and FSH levels with exaggerated responses of LH to LRH were observed in most patients during treatment, whereas the response of LH to LRH was normal in about half of the patients after treatment. Our findings suggest that hyperprolactinemia in patients treated with SLP or MCP may be in part the cause of both galactorrhea and menstrual abnormalities, and that these symptoms can be reversed by stopping treatment, provided the patients have not taken the drugs for longer than a year.

Adult

[Drug-induced hyperprolactinemia and galactorrhea].

A 21 year old female treated for recurring gastric troubles with dopamine-antagonists (domperidone, metoclopramide) developed a clinically manifest hyperprolactinemia (3055 microU/l; normal value < 650 microU/l) with galactorrhea only two days after a new two day course of metoclopramide. The drug was withdrawn and within days mastodynia and galactorrhea subsided. A control of plasmatic prolactin two weeks later yielded a normal value (358 microU/l). After administration of metoclopramide or domperidone hyperprolactinemia is regularly observed and galactorrhea has been described earlier. It is unclear why this patient inspite of repeated administration of one dopamine antagonist remained asymptomatic whereas the other after a short time and only a few doses led to galactorrhea. It is conceivable that differences in passage into the cerebrospinal fluid or the better penetration of the blood-brain barrier favored the development of galactorrhea under metoclopramide. This case served to discuss the pathophysiologic background of drug-induced hyperprolactinemia.

Adult

Antecedent factors and outcome in amenorrhea-galactorrhea.

One hundred seventeen patients with amenorrhea and galactorrhea or hyperprolactinemia were evaluated with regard to antecedent factors, results of investigations, and management. Full details of the outcome of prolonged follow-up were available for 104 patients. Patients who developed amenorrhea-galactorrhea after withdrawal of oral contraceptives or postpartum had a lower incidence of pituitary adenomas than did those who developed amenorrhea-galactorrhea spontaneously. Six of a total of 40 tumors were detected only during the follow-up period. This study suggests that patients with spontaneous amenorrhea-galactorrhea have a greater risk of developing a detectable pituitary adenoma than do those with postpill or postpartum symptoms. However, patients with a microadenoma are more likely to have had postpill onset of hyperprolactinemia. Plasma prolactin (PRL) in patients with postpill amenorrhea-galactorrhea increased in proportion to the duration of oral contraceptive use.

Adenoma

Effect of bromo-ergocryptine on serum hPRL, hLH, hFSH, and estradiol 17-beta in women with galactorrhea-amenorrhea.

Fourteen women with amenorrhea-galactorrhea were treated with bromo-ergocryptine. Serum prolactin hPRL, hLH, hFSH, estradiol 17-beta (E2), and progesterone values were determined before and during treatment. No consistent pretreatment hormonal pattern was found. During treatment hPRL levels fell in 13 of 14 patients, and E2 rose in 12 of 14 patients. Levels of hLH became normal, and amounts of hFSH did not change. Galactorrhea lessened in all cases and ceased in 11. Menses resumed in 11 patients and 3 women became pregnant. Cessation of galactorrhea and resumption of menses occurred irrespective of initial hPRL or hLH levels. It is suggested that improvement of galactorrhea and resumption of menses in some patients with normal hPRL values are the result of increased serum E2 levels and may be due to a direct action of bromo-ergocryptine on the ovary. Bromo-ergocryptine may also be effective in treatment of amenorrhea, unassociated with galactorrhea or elevated hPRL levels.

Adult

Serum prolactin levels in galactorrhea.

Some patients with galactorrhea will have normal serum prolactin levels but many will have elevated serum prolactin levels. The galactorrhea may be due to drug ingestion, nipple afferent nerve stimulation, nonneoplastic disease or injury, and intracranial tumors. Serum prolactin levels were measured by radioimmunoassay in 17 women with galactorrhea. Levels 5 and 6 times normal values were found in two women who had proved pituitary adenomas. The latter conditions must be strongly considered and functional tests may help in diagnosis prior to enlargement of a prolactin-secreting tumor to the size where changes in the sella are seen on x-ray or visual field changes occur. If galactorrhea persists when no evidence of tumor can be found, the patient must be periodically re-evaluated, as the tumor may have been too small for detection at the time of the previous examination.

Adenoma

Detection, evaluation, and treatment of pituitary microadenomas in patients with galactorrhea and amenorrhea.

Over a period of two and a half years, 34 women with galactorrhea or amenorrhea, all with an abnormal sellar polytomogram, underwent transsphenoidal microsurgical exploration of the sella. Eighteen women and microadenomas (less than or equal to 1 cm. in diameter), seven had macroadenomas (greater than than 1 cm. in diameter), and five had unidentified lesions. Only one women had a normal pituitary gland. Three women had cryosurgery without biopsy. Preoperatively, hyperprolactinemia occurred in 24 of 25 women with adenomas and two of five with nonadenomatous lesions. There were no operative deaths. Significant morbidity occurred in only three patients, none of whom had microadenomas. Postoperatively, menses resumed in 16 of the 17 women with microadenomas and in two of the seven with macroadenomas who presented with amenorrhea. Galactorrhea disappeared in 15 of the 17 women with microadenomas and in four of the seven with macroadenomas who presented with galactorrhea. In five patients with unidentified lesions, a return of menses occurred in two of four with previous amenorrhea, and galactorrhea abated in two of three who presented with lactation. We conclude that sellar polytomography in women with hyperprolactinemia is a useful technique technique for the diagnosis of pituitary adenomas, a lesion which may occur more frequently than previously realized. In addition, transsphenoidal microresection of microadenomas is safe and effective.

Adenoma

Effects of nocturnal hyperprolactinemia on ovarian luteal function and galactorrhea.

To determine the effects of nocturnal hyperprolactinemia on luteal function and galactorrhea we studied six diurnal normoprolactinemic women with regular menstrual cycles. The diurnal serum levels of prolactin (PRL), luteinizing hormone (LH) and progesterone (Prog) and the nocturnal PRL levels at 1 h intervals were determined throughout the first menstrual cycle. Four of the women were nocturnally normoprolactinemic and two showed nocturnal hyperprolactinemia and low luteal progesterone values. In the second menstrual cycle, they were given metoclopramide (10 mg) at midnight before sleep every day, and their serum levels of PRL, LH and Prog were determined by the same protocol as in the first cycle. During treatment with metoclopramide, all the women showed nocturnal hyperprolactinemia, but their diurnal PRL levels remained within the normal range. Low luteal Prog values were observed in all of them and the peak LH levels decreased in all four nocturnally normoprolactinemic women. They had galactorrhea but neither of the nocturnally hyperprolactinemic women had galactorrhea. These results suggest that nocturnal hyperprolactinemia is a cause of luteal insufficiency and galactorrhea.

Adult

Galactorrhea: a study of 235 cases, including 48 with pituitary tumors.

An analysis of 235 patients with galactorrhea (5.5 per cent males) showed that 20 per cent of all patients, and 34 per cent of women with associated amenorrhea, had radiologically evident pituitary tumors; these patients had the highest serum prolactin concentrations. The largest single group (32 per cent) consisted of women with idiopathic galactorrhea without amenorrhea; prolactin was normal in 86 per cent of these cases. Five patients had the empty-sella syndrome. Prolactin response was tested in selected patients by thyrotropin-releasing hormone, chlorpromazine, L-dopa, 24-hour sampling and other means. Tests with thyrotropin-releasing hormone were most useful in identifying patients with pituitary tumors. Surgery and radiotherapy lowered prolactin to a similar degree in patients with tumor, but galactorrhea, and amenorrhea often persisted after treatment. The ergot derivatives, bromergocryptine and lergotrile mesylate, lowered prolactin in all 18 patients with idiopathic hyperprolactinemia or pituitary tumor, stopped galactorrhea in over 50 per cent, restored menses in over 70 per cent, and allowed pregnancy in three.

Acromegaly

Cyproheptadine in the management of the galactorrhea-amenorrhea syndrome.

We evaluated long-term treatment with the antiserotonergic agent cyproheptadine in the management of the galactorrhea-amenorrhea syndrome. Fifteen women with a mean initial serum prolactin of 37 +/- 7 ng/mL received 16 to 24 mg of cyproheptadine daily; they had a significant decrease in prolactin concentration at 8 and at 16 weeks (P less than 0.01). Gonadotropin responses were variable, but no significant changes were recorded during treatment. Ten of the 15 women had menstrual bleeding while receiving cyproheptadine, seven had decreased galactorrhea, and two had cessation of galactorrhea. The side effects of treatment were transient drowsiness and weight gain. We conclude that long-term treatment of the galactorrhea-amenorrhea syndrome with cyproheptadine is effective in lowering serum prolactin in patients with mildly elevated or normal levels. Its effect on fertility remains to be ascertained.

Adult

[Endocrinological aspect of galactorrhea and lactation in relation to the cytology of breast secretion].

The concentration of prolactin in the plasma and the cytologic smears of the mammary extraction were analysed in 67 patients with galactorrhea. In 38 patients galactorrhea was couple with amenorrhea. Out of 67 patients with galactorrhea, 32 had hyperprolactinemia (68.6 +/- 14.4 ng/ml) along with low estrogen (14.6 +/- 3.8 ug/24 hours) and aonadotropin (FSH 6.2 +/- 2.0, LH 8.5 +/- 2.6 mIU/ml) values. In 48 out of 67 patients galactorrhea seceded under the therapy of Parlodel (bromocriptine). Out of 13 patients waiting pregnancy, 9 showed a restitution ofa the ovulatory cycle and 2 became pregnant. In the group of parturients it proved possible to suppress ablactation by estrogenic-and androgenic preparations (Ablacton) without a decrease in the prolactin concentration, while Parlodel brought about ablactation with a decrease of the prolactin concentration to normal values as early as 24 hours following the application of its first dose. In 6 patients with hyperprolactinemia and low estrogaen and gonatropin values an increase in the concentration of LH and FSH after 100 micrograms LH--RH i. m. was observed. In the cytologic smears of the mammary excretion there were no atypical or malignant cells.

Adolescent

Intrasellar subarachnoid herniation or empty sella associated with galactorrhea.

Eight of 115 patients with empty sella had concurrent galactorrhea. All 8 patients had abnormal sellae, and the diagnosis of empty sella was made by polytome pneumoencephalography. There were no obvious endocrine dysfunctions, but 2 patients had elevated prolactin levels. One mechanism for production of galactorrhea may involve compression of the hypothalamus and/or pituitary stalk; this was suggested by most of our observations. There may be a coincidental association of empty sella with galactorrhea, and this association is probably more common than previously noted. Evaluation of patients with galactorrhea and abnormal sellae by polytome pneumoencephalography is emphasized.

Adolescent