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[A clinical study on the characteristics of galactorrhea-amenorrhea (especially of drug-induced galactorrhea-amenorrhea].

The clinical characteristics of women with galactorrhea and amenorrhea induced by drugs were studied. In addition, hyperprolactinemia was, experimentally, induced by sulpiride in women, and their endocrinological backgrounds were studied. The findings suggested that the mechanism of amenorrhea due to hyperprolactinemia was primarily the reduction of steroidogenesis in the ovary, and also the disturbance of positive feedback to the hypothalamus. Hyperprolactinemia was induced in rats by sulpiride, and the effect on pituitary lactotrophs was studied. In the hyperprolactinemic state caused by PIF inhibition by sulpiride it was indicated that there was a limit to prolactin secretion and release by the pituitary gland. It was also confirmed that a large amount of estradiol exerted a stimulating action directly on the PRL-producing cells of the pituitary gland.

Amenorrhea↗

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↗

Long-term follow-up of women with amenorrhea-galactorrhea treated with bromocriptine.

The present study is aimed at investigating whether long-term use of bromocriptine on patients affected by amenorrhea and galactorrhea may improve the clinical picture after discontinuation of treatment. For this reason 26 patients with amenorrhea and galactorrhea have been studied. Sixteen had high PRL values and 10 were normoprolactinemic. The normoprolactinemic patients underwent a TRH test. All the patients underwent computed skull axial tomography (CT scan) and were treated with bromocriptine, at a daily dosage variable from 2.5 to 10 mg for an average period of 26 months. After discontinuation of treatment, follow-up was carried-out for 20 months. Eighty-seven percent of the patients affected by amenorrhea, galactorrhea and hyperprolactinemia had regular menses, in 75 of the patients galactorrhea completely disappeared. Of the ten patients with normoprolactinemic amenorrhea and galactorrhea, only those who positively responded to the TRH test had regular menstruation and showed disappearance of galactorrhea. Upon discontinuation of treatment amenorrhea recurred in 68% of the cases whereas galactorrhea recurred in 80%. CT scans revealed disappearance of 3 microadenomas and reduction in size of the macroadenoma. Long-term use of bromocriptine represents the first choice treatment for the syndrome of galactorrhea-amenorrhea. In case of relapse, treatment must be continued for an undefined period of time.

Adenoma↗

Prolactin concentration in milk and plasma of puerperal women and patients with galactorrhea.

Prolactin (PRL) concentration was estimated in milk and blood of women with various types of galactorrhea (n = 53) and was compared with lactating (n = 17) and normally menstruating women (n = 36). Mean milk (+/- SD) PRL concentration in lactating women (160 +/- 66 micrograms/l) was similar to that of galactorrhea due to pituitary adenoma (149 +/- 87 micrograms/l, n = 24), thyroid dysfunction (193 +/- 72 micrograms/l, n = 8), functional causes (192 +/- 91 micrograms/l, n = 10) or recent pregnancy (198 +/- 44 micrograms/l, n = 2), but higher than that of sex steroid-induced galactorrhea (85 +/- 53 micrograms/l, n = 9). Plasma PRL concentration in lactating women (208 +/- 102 micrograms/l) was higher than in normal control women (14 +/- 5 micrograms/l) and patients with galactorrhea due to thyroid dysfunction (36 +/- 15 micrograms/l), functional causes (16 +/- 8 micrograms/l), drugs (20 +/- 4 micrograms/l), recent pregnancy (22 +/- 3 micrograms/l) or pituitary adenoma (145 +/- 53 micrograms/l). The milk to plasma PRL concentration ratio was 0.8 +/- 0.4 in lactating women and 1.1 +/- 0.7 in patients with adenoma but significantly higher (p = 99% two-sided) in galactorrhea due to thyroid dysfunction (4.4 +/- 2.1), drugs (3.4 +/- 1.1) or functional causes (12.3 +/- 4.3). Bromocriptine administration reduced PRL in both fluids. It is concluded that in women with galactorrhea milk PRL concentration is similar to that of nursing mothers, but plasma levels of this hormone are significantly lower than that of the latter group in all but the pituitary adenoma related galactorrheas.

Adenoma↗

[Study on galactorrhea-amenorrhea syndrome (GAS) with special reference to normoprolactinemic GAS].

In order to clarify the mechanism(s) which causes galactorrhea and amenorrhea in patients with Galactorrhea-Amenorrhea Syndrome (GAS) (Group A, n = 20), composed of Chiari-Frommel Syndrome (CFS) (Subgroup I, n = 3), Argonz-del Castillo Syndrome (ADCS) (Subgroup II, n = 5) and Drug-induced Galactorrhea-Amenorrhea (DIG) (Subgroup III, n = 12), we analysed basal plasma prolactin (PRL) and gonadotropin levels and their responsiveness to TRH and LH-RH, respectively in GAS patients. In addition, another group of galactorrhea patients without amenorrhea (Group B, n = 29) was selected, and further divided into three subgroups; subgroup I (n = 7) with persisting postpartum lactation, subgroup II (n = 7) of idiopathic galactorrhea, and subgroup III (n = 15) induced by drug administration. There were found unexpectedly high frequencies of normoprolactinemic patients (less than 23.7 ng/ml) in 40% of GAS (66.7% in CFS, 40% in ADCS, and 33.3% in DIG). The PRL responsiveness to TRH, evaluated by % delta PRL (peak PRL - basal PRL/basal PRL X 100), tended to be high in ADCS and DIG (group after discontinuation of drugs) compared with those of normal subjects (n = 12) and patients with primary hypothyroidism (n = 21). PRL response was almost normal in CFS or DIG (group during drug administration). Basal level of plasma gonadotropin in GAS was comparable to that of normal subjects. However, responsiveness of gonadotropin to LH-RH in GAS tended to be high compared with that of normal subjects. The patients in group B (subgroup I-III) demonstrated almost parallel responses of PRL and gonadotropin, respectively, to those of corresponded subgroups in group A. From the present results, we concluded that; 1) It seems likely that frequency of normoprolactinemic patients in GAS (Group A) is surprisingly high. 2) A still unclarified mechanism(s) for the occurrence of galactorrhea, not explained solely by plasma radioimmunoassayable PRL level and/or hyperresponsiveness of PRL to stimuli, may operate on a considerably large number of group A patients. 3) Decreased gonadotropin secretion at pituitary level seems not to be a main cause of menstrual abnormality in group A patients. 4) The same mechanism(s) as in group A patients may cause galactorrhea in group B patients.

Adolescent↗

Galactorrhea in subclinical hypothyroidism.

Galactorrhea was found in 5 patients with subclinical hypothyroidism. The galactorrhea consisted of the discharge of a few drops of milk only under pressure. Serum T4 was in the lower level of the normal range, but serum T3 was normal (T4: 6.3 +/- 1.2 micrograms/dl, T3: 113 +/- 7 ng/dl). Basal serum TSH and PRL were slightly increased only in 2 and 1 cases, respectively. The PRL responses to TRH stimulation were exaggerated in all cases, although the basal levels were normal. An enlarged pituitary gland was observed in 1 patient by means of CT scanning. All patients were treated by T4 replacement. In serial TRH tests during the T4 replacement therapy, the PRL response was still increased even when the TSH response was normalized. Galactorrhea disappeared when the patients were treated with an increased dose of T4 (150-200 micrograms/day). Recurrence of galactorrhea was not observed even though replacement dose of T4 was later decreased to 100 micrograms/day in 4 cases. In patients with galactorrhea of unknown origin, subclinical hypothyroidism should not be ruled out even when their serum T4, T3, TSH and PRL are in the normal range. The TRH stimulation test is necessary to detect an exaggerated PRL response, as the cause of the galactorrhea. To differentiate this from pituitary microadenoma, observation of the effects of T4 replacement therapy on galactorrhea is essential.

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↗

Distribution of growth hormone isoforms in sera from women with normal ovarian function, galactorrhea, and normoprolactinemia.

OBJECTIVE: To demonstrate if GH concentrations and molecular heterogeneity of GH correlates with the presence of galactorrhea in normoprolactinemic women with normal ovarian function. DESIGN: Aliquots of sera from women with normal ovarian function and normoprolactinemic galactorrhea were subjected to gel filtration chromatography, and the fractions were assayed for GH by the use of radioimmunoassay. Molecular weight of isoforms was calculated on a calibration curve obtained with molecular markers. The molecular variants were characterized on the basis of elution volume, molecular weight (MW), and partition coefficient. RESULTS: Basal serum GH levels were moderately elevated in all six normoprolactinemic women exhibiting galactorrhea. Chromatographic study of sera from these normoprolactinemic women showed the predominance of 40 to 50 kd molecular forms of GH as well as some very low MW GH isoforms. This pattern was different from that obtained in sera from normal women without galactorrhea who presented a predominance of heavier (> 60 kd) isoforms eluted before the GH labeled standard. The monomeric forms were present in less proportion but there was no significant difference as compared with galactorrheic group. CONCLUSIONS: Our investigation demonstrated elevated GH basal serum levels is normoprolactinemic women with galactorrhea, and chromatography in gel showed a low proportion of the large MW GH variants associated with a higher proportion of the dimeric forms and very low MW forms of GH. This is different from normal women without galactorrhea who had a predominance of heavier MW GH variants and lesser proportion of < 16 kd isoforms. It is concluded that an increased GH secretion may be responsible for abnormal lactation despite normal PRL levels in some women with normal ovarian function.

Adult↗

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↗

Case-control study of galactorrhea and its relationship to the use of oral contraceptives.

A case-control study was performed to determine the relationship between galactorrhea and the use of oral contraceptives as well as other risk factors. The cases included all 109 Olmsted County residents who satisfied the diagnostic criteria for galactorrhea between 1970 and 1980. Control subjects were selected from a sampling frame of all medical registrations and matched to the cases by age, year, and residency. Pituitary adenomas were strongly associated with galactorrhea, as the relative risk was 23.2 (95% confidence interval 2.0 to 90.0). In galactorrhea cases without pituitary adenomas there was an association with oral contraceptives (ever use versus never use), as the relative risk was 2.3 (95% confidence interval 1.3 to 4.4). Among current users of oral contraceptives, the risk of galactorrhea was not increased, but there was a trend of diminishing risk with duration of use. The estimate of relative risk was 3.1 after discontinuation of oral contraceptive use and was highest for the first year after discontinuation (5.5), compared with a year or more after discontinuation (2.1). Thus, galactorrhea was associated with the cessation of oral contraceptives.

Adenoma↗

Galactorrhea and hyperprolactinemia during treatment of polycystic ovary syndrome.

The serum concentration of prolactin and the presence of galactorrhea were evaluated systematically in a prospective study of the effect of medroxyprogesterone acetate (MPA) in polycystic ovary syndrome (PCO). In 21 patients, the diagnosis of PCO was made by laparoscopy. Three women presented with galactorrhea and increased prolactin levels, 2 had galactorrhea with normal prolactin levels, and 3 had an isolated elevation in the serum concentration of prolactin. Treatment with MPA induced galactorrhea in 10 additional patients. Elevated levels of prolactin were detected in 18 of the patients during treatment. There was no correlation between the score for galactorrhea and the level of prolactin. Tomograms of the sella turcica were abnormal in 3 of 8 patients with hyperprolactinemia. The authors conclude that galactorrhea and/or hyperprolactinemia are important side effects of MPA in patients with PCO.

Adolescent↗

Risk factors for secondary amenorrhea and galactorrhea.

OBJECTIVE: Analyses were undertaken to identify factors that may predispose women to secondary amenorrhea or galactorrhea, frequent sources of abnormal reproductive function. METHODS: Data were gathered from interviews with 252 women with secondary amenorrhea or galactorrhea from four clinical centers, along with neighborhood controls matched to each case. Univariate comparisons were made for clinical and demographic factors of the study subjects. RESULTS: Patients with amenorrhea and normal prolactin (PRL) levels and their matched controls tended to be younger than those with amenorrhea and elevated PRL or than menstruating patients with galactorrhea alone and their matched controls. Patients with amenorrhea and normal PRL also were significantly more educated and were older at menarche than their controls, while amenorrhea patients with elevated PRL or patients with galactorrhea alone did not differ significantly from their controls in age at menarche or educational level. More patients with galactorrhea alone had reported menstrual pain to their physicians and had significantly longer menstrual periods than their matched controls. Patients with galactorrhea alone also weighed more than their controls 2 years prior to diagnosis, a difference that remained after stratification by parity, although only statistically significant among women who had had one or two pregnancies. Finally, significantly fewer patients with amenorrhea than controls were smokers. Thus, these disorders may not be due to anti-estrogenic effect or to low estrogen levels which have been associated with smoking.

Adolescent↗

'Witch's milk'. Galactorrhea in the newborn.

For a five month period, infants examined on admission and discharge from the newborn nursery and at two-week and two-month well-baby visits were examined for breast nodule size and the presence of galactorrhea. Nine hundred eighty-four examinations were performed on 640 children. Forty-five examinations (4.6%) on 38 infants revealed galactorrhea. "Witch's milk" was noted at all ages studied, including 1.8% of examinations at 2 months of age. All the infants with galactorrhea were born at term, with neither sex predominating. Children with galactorrhea had breast nodules significantly larger than those of children without galactorrhea. None of these infants was hypothyroid. This study concludes that witch's milk is a common occurrence, associated with larger than average breast nodules, and may persist until 2 months of age in normal newborns.

Female↗

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↗

Galactorrhea as the sole presenting symptom of a posterior third ventricular epidermoid cyst.

BACKGROUND: Brain tumors that are remote from the sellar and parasellar region rarely produce galactorrhea. CASE DESCRIPTION: Galactorrhea was the sole presenting symptom in a patient with a posterior third ventricular epidermoid cyst. On investigation, her serum prolactin level was mildly elevated. After radical excision of the tumour, the spontaneous galactorrhea stopped and the serum prolactin level decreased. CONCLUSION: Because of the clinical and biochemical response seen after surgery, we speculate that the galactorrhea was caused by the presence of the tumor. We postulate that the pressure exerted by the tumor on the diencephalic structures was probably the cause of galactorrhea in our patient.

Adult↗