Conservative management of suspected prolactin secreting pituitary adenoma during pregnancy

Seventeen women with prolactin levels of 100 ng/ml and above suspected of harboring prolactin-secreting pituitary adenoma, form the basis of this study. Ten patients had radiological signs of an adenoma while in 7 the radiological criteria for such a diagnosis were not fulfilled. Ovulation and pregnancy were induced with bromocriptine in all 17 patients. They were carefully observed during pregnancy and following delivery. All gave birth to full-term babies after uneventful pregnancies, except for one patient who experienced intrauterine fetal death at 31 wk of gestation. It is our policy that women with suspected intrasellar prolactin-secreting pituitary adenoma be allowed to conceive and give birth without previous surgical intervention. The patient should be closely followed during pregnancy for clinical symptoms of enlargement of the tumor, including periodic visual field examinations. In cases of neurologic or ophthalmologic complications, surgery or bromocriptine administration without interruption of pregnancy is advocated, or if lung maturity is achieved, delivery should be induced.     

The outcome of pregnancy in patients with treated and untreated prolactin-secreting pituitary tumors

Few data document pregnancy risks in patients with prolactin-secreting pituitary tumors, particularly risks relating to the likelihood and severity of increased tumor size. This study presents three groups of women with such lesions. Group 1 consisted of 47 women with transsphenoidal resection who were euprolactinemic postoperatively. Of this group 20 of 22 previously infertile women conceived 25 pregnancies. Group 2 was composed of 17 women who were operated upon but in whom prolactin was still raised (greater than 50 ng/ml) postoperatively and bromocriptine was subsequently used. Seven of these 17 patients were previously infertile, and six of the seven have conceived. In group 3 22 infertile women with small pituitary tumors were not operated upon but received bromocriptine. Eighteen of these patients have achieved 24 pregnancies. Methods of diagnosis, surveillance during pregnancy, and medical and surgical management are presented. Only two patients, both in group 3, developed signs of expanding tumor size in pregnancy.     

Outcome of Treatment with Bromocriptine in Patients with Hyperprolactinaemia

Results in 136 hyperprolactinaemic women who presented with infertility, amenorrhoea, menstrual irregularities and/or galactorrhoea are reported. There was radiographic evidence of pituitary microadenoma in 21 (15.4%) patients and 5 (3.7%) had macroadenoma. Four patients were taking antidepressants, 2 antihypertensive drugs and 7 had taken oral contraceptives for a period of 6 months to 5 years. The remaining patients had no obvious cause for elevated prolactin levels. Patients with pituitary adenoma had a significantly higher (p less than 0.001) baseline serum prolactin level (182 +/- 4.6 ng/ml) than those with no adenoma (59.2 +/- 4.2 ng/ml). All patients in the study were treated with bromocriptine (2.5-10 mg) to normalize serum prolactin or to achieve a pregnancy. The patients without an adenoma required a significantly smaller dose of bromocriptine (2.5-5.0 mg) (p less than 0.005) than those with an adenoma. Galactorrhoea disappeared in all 64 patients within 2-4 months of treatment, sixty-six (71%) of the 93 patients who desired pregnancy achieved it within 3 to 8 months of bromocriptine therapy; 32 of these patients received additional treatment with clomiphene and human chorionic gonadotrophins for induction of ovulation. In the remaining 70 patients menstruation became regular and ovulation was evident in 40% of them. There was no significant difference in the pregnancy rate between the patients with or without pituitary adenoma. Similarly, presence of galactorrhoea or a high level of prolactin did not influence the pregnancy rate. No complications were observed during pregnancy related to pituitary adenomas; 8 (12%) pregnancies ended in first trimester abortion. No lethal congenital fetal abnormalities were observed in the patients treated with bromocriptine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Rapid re-enlargement of a macroprolactinoma after initial shrinkage in a young woman treated with bromocriptine

We report the case of a macroprolactinoma in a 32-year-old woman, who presented with secondary amenorrhea, galactorrhea, increased plasma prolactin level (3259?ng/ml), headache and bi-temporal visual field defect. Magnetic resonance imaging showed a large pituitary tumor. The patient responded well to bromocriptine (7.5?mg/day) with improvement of clinical symptoms and normalization of plasma prolactin within a few weeks. After 4 months of treatment, tumor size was also reduced markedly. During continued treatment at the same dose of bromocriptine the plasma prolactin level remained normal, but after 8 months of treatment the patient suddenly complained of worsening of her visual fields, and magnetic resonance imaging indicated re-enlargement of the tumor. Bromocriptine was discontinued and transsphenoidal pituitary surgery was performed. After surgery the visual field defect improved, but postoperative plasma prolactin level (1104?ng/ml) and magnetic resonance imaging indicated a residual tumor. Postoperative treatment with quinagolide (0.15?mg/day) resulted in disappearance of all clinical symptoms, normalization of prolactin level and a reduction in size of the residual tumor. This case demonstrates that a dissociation of the inhibitory effect of bromocriptine on tumor size and prolactin level may rarely develop during the course of drug treatment in a patient with macroprolactinoma.     

Rapid re-enlargement of a macroprolactinoma after initial shrinkage in a young woman treated with bromocriptine.

We report the case of a macroprolactinoma in a 32-year-old woman, who presented with secondary amenorrhea, galactorrhea, increased plasma prolactin level (3259 ng/ml), headache and bi-temporal visual field defect. Magnetic resonance imaging showed a large pituitary tumor. The patient responded well to bromocriptine (7.5 mg/day) with improvement of clinical symptoms and normalization of plasma prolactin within a few weeks. After 4 months of treatment, tumor size was also reduced markedly. During continued treatment at the same dose of bromocriptine the plasma prolactin level remained normal, but after 8 months of treatment the patient suddenly complained of worsening of her visual fields, and magnetic resonance imaging indicated re-enlargement of the tumor. Bromocriptine was discontinued and transsphenoidal pituitary surgery was performed. After surgery the visual field defect improved, but postoperative plasma prolactin level (1104 ng/ml) and magnetic resonance imaging indicated a residual tumor. Postoperative treatment with quinagolide (0.15 mg/day) resulted in disappearance of all clinical symptoms, normalization of prolactin level and a reduction in size of the residual tumor. This case demonstrates that a dissociation of the inhibitory effect of bromocriptine on tumor size and prolactin level may rarely develop during the course of drug treatment in a patient with macroprolactinoma.     

Outcome and long-term effects of pregnancy in women with hyperprolactinaemia.

Twenty-four women with high circulating prolactin became pregnant on 39 occasions, of which 32 ended in delivery. Sixteen patients showed radiological evidence of pituitary tumour, 6 exhibited a normal CT and 2 had an empty sella. The pregnancies were induced in 4 patients after successful pituitary surgery, in 3 after surgery and medical treatment, and in the rest by bromocriptine (16) long-acting repeatable bromocriptine (1) and methergoline (1). No major complications related to hyperprolactinaemia or its treatment were observed during pregnancy in the patients or offspring. Prolactin after pregnancy was lower than before (basal 95 micrograms/l, after 1st pregnancy 38 micrograms/l P < 0.002, after 2nd pregnancy 24 micrograms/l P < 0.005 compared to basal prolactin); this prolactin reduction tended to be greater in the 9 multiparous patients, but did not attain statistical significance, probably because the number of multiparous patients was too small. A new empty sella developed after delivery in 4 women and persisted in another 2, all of which were medically treated; prolactin fell in all 6 cases normalizing in 3; 4 of these patients had undergone two or more pregnancies. The mean period of follow-up from the last pregnancy was 41.6 months (8-101). These data suggest that pregnancy may hasten a tendency to spontaneous improvement of hyperprolactinaemia, and multiparity may be beneficial in this way.     

Visual and neurological disturbances accompanying with pregnancies of hyperprolactinemic patients

Twenty-three hyperprolactinemic infertile cases become pregnant after surgical treatment and/or bromocriptine administration, and 18 of them accomplished normal full-term deliveries. Serial ophthalmological examination which had been performed monthly throughout pregnancy revealed that four cases bearing pituitary adenomas developed visual disturbances which manifested themselves in the latter part of gestational period. The objective signs detected in these cases were bitemporal hemianopsia, temporal and nasal visual defects and the disappearance of central isopter. Another patient with microadenoma complained of headache at 16 weeks of gestation and it became more severe as gestation progressed. Bromocriptine (1.25 mg/day) was effective in diminishing this symptom. Although all these cases recovered from visual disturbances and headache after delivery, two of them were operated on transsphenoidally when radiological evidence of pituitary enlargement was found in the postpartum period. It is generally accepted that nearly 20% of hyperprolactinemic patients have pituitary adenomas. In view of the limited accuracy of techniques used in diagnosing pituitary tumor, it is legitimate to postulate that most hyperprolactinemic infertile patients have microadenoma to some extent. For this reason, a detailed follow up of visual field and neurological signs throughout pregnancy of hyperprolactinemic patients is important in early detection of changes in pituitary size.     

Prolactin and placental hormone levels during pregnancy in prolactinomas

Prolactin (PRL) and the placental hormones, estradiol (E2), estriol (E3), progesterone (PG), chorionic gonadotropin (HCG), and placental lactogen (HPL) were serially measured throughout pregnancy and early postpartum in three patients with prolactinomas in whom pregnancy was achieved by one of the three modalities of treatment: bromocriptine administration (patient I), irradiation of the pituitary (patient II), and human gonadotropin administration after excision of the adenoma (patient III). It was found that PRL in patient I reached the high pretreatment levels in the 2nd month of pregnancy and increased to further abnormal concentrations in the last 2 months, but fell at the onset of labor 1 week after an episode of severe headache. The PRL changes in this patient were attributed successively to tumor expansion and apoplexy. In patient II PRL decreased after irradiation, but was not normalized. During pregnancy it remained moderately increased presenting minor fluctuations. The third patient with postoperative GH and TSH pituitary insufficiency had low pretreatment PRL levels which remained practically unchanged throughout pregnancy. The two last patients gave birth to identical twins. The placental hormones were found normal in all three patients but E2 and PG were relatively increased during the last weeks of pregnancy in the twin pregnancies. Amniotic fluid and umbilical cord PRL and E2 concentrations were normal. The patients presented agalactia and suckling did not induce a PRL increase. We conclude that a) serial PRL measurements during pregnancy reflect the changes occurring in the prolactinomas and are essential in monitoring the patients bearing these tumors; b) maternal hyperprolactinemia or failure of PRL to increase during pregnancy do not influence either the secretion of placental hormones or PRL concentration in amniotic fluid and the newborn; and c) hyperprolactinemia during pregnancy is of maternal pituitary origin.     

Pregnancy in hyperprolactinemic infertile women treated with vaginal bromocriptine: report of two cases and review of the literature.

Vaginal bromocriptine has proven safe and effective in treating hyperprolactinemic women. However, there has been no long-term clinical assessment regarding the influence of daily vaginal bromocriptine administration on the ability to conceive. This article presents two cases of successful pregnancy resulting from this alternative treatment. An infertile woman with an empty sella and hyperprolactinemia was treated with vaginal bromocriptine because of intolerance to oral administration. Prolactin levels were quickly normalized and no side effects occurred. Repeated postcoital tests during treatment proved normal. Twelve months later, the patient conceived. The therapy was discontinued during pregnancy, without complications. Although bromocriptine treatment was not resumed after delivery, postpartum prolactin levels were lower than before treatment and magnetic resonance imaging revealed an unchanged empty sella. Another patient with infertility and pituitary microadenoma with intolerance to oral dopaminergic agonists received the same treatment. Prolactin quickly fell to within the normal range. Vaginal bromocriptine was well tolerated and postcoital test results were not impaired. Tumor regression occurred and 10 months later the patient conceived. Despite bromocriptine withdrawal, no significant complications occurred during pregnancy. It can therefore be concluded that a couple's fertility does not appear to be significantly affected by the persistent local presence of bromocriptine.     

Hyperprolactinemic response after bromocriptine withdrawal in women with prolactin-secreting pituitary tumors

In patients with prolactin (PRL)-secreting tumors, plasma PRL concentrations after discontinuation of bromocriptine therapy have been used clinically as an index of tumor activity. To investigate the pattern of PRL response under these conditions, seven women on chronic bromocriptine therapy for PRL-producing pituitary tumors were followed with serial PRL determinations for 2 months after bromocriptine withdrawal. In these patients, peak PRL concentrations were achieved 28.1 days (mean; range, 14 to 49 days) after bromocriptine discontinuation. However, PRL concentrations did not usually plateau until at least 40 days after cessation of therapy, and the pattern of PRL response was highly variable. Because of the inconsistent pattern of serum PRL response during the first 40 days after discontinuation of bromocriptine, decisions regarding tumor activity based on PRL concentrations should not be made until at least 6 weeks after withdrawal of the drug.     

Indomethacin for the treatment of symptomatic leiomyoma uteri during pregnancy.

Pain secondary to carneous degeneration is the most common complication of leiomyoma uteri during pregnancy. Conventional therapy utilizing bed rest and parenteral narcotic analgesics may often be ineffective. We retrospectively reviewed seven cases of degenerating fibroids complicating pregnancy where the prostaglandin synthetase inhibitor, indomethacin (25 mg orally every 6 hours), was used to treat symptoms of pain. In all cases, relief of symptoms was achieved within 48 hours of initiation of therapy. Two patients required a second course of therapy, and one patient required a third course. Mean duration of therapy was 12 days. One fetus developed transient constriction of the ductus arteriosus and transient oligohydramnios. Two pregnancies aborted, one at 22.9 and one at 22.3 weeks; however, no perinatal complications were directly attributable to indomethacin. The five term deliveries were of healthy normal infants. These retrospective data suggest that indomethacin may be effective in the treatment of pain associated with degenerating uterine leiomyomas in pregnancy.     

Bromocriptine therapy of prolactinoma in pregnancy

A report is given about the course of pregnancy and delivery of two patients with prolactin-producing pituitary adenomas and therapy with bromocriptine. Different views about treatment of prolactinomas in pregnancy are discussed. Pregnancy care has to be in close cooperation between endocrinologists and obstetricians.     

The effects of pregnancy on patients with hyperprolactinemia

Seventy women with amenorrhea with or without galactorrhea associated with high serum prolactin levels and radiologic evidence of pituitary tumors were treated with transsphenoidal tumor resection. The prolactin level was measured in 29 patients before pregnancy, at 3 months post partum or cessation of lactation, and at 6-month intervals thereafter. The results were compared to those of 18 patients who had hyperprolactinemia but no demonstrable radiologic evidence of a pituitary tumor and who responded to bromocriptine and conceived. Our investigations showed that operation resulted in normalization of serum prolactin levels in 74% of patients. Forty of the 49 patients less than 36 years old conceived (80%). Five of 29 patients who were studied before and after operation as well as after delivery showed an increase in serum prolactin levels post partum and persistent amenorrhea suggesting recurrence. Six of the 18 patients who became pregnant after bromocriptine also showed a significant rise in serum prolactin levels above the treatment level. None of the patients in the two groups developed visual changes or symptoms or radiologic changes during pregnancy. These results showed that transsphenoidal operation has a high incidence of success, but some patients may show a rise of serum prolactin levels and persistent amenorrhea after pregnancy or passage of time, suggesting recurrence. Some patients who become pregnant after bromocriptine therapy may have further rises in prolactin greater than pretreatment levels. Follow-up of these patients is indicated.     

Current treatment issues in female hyperprolactinaemia

High prolactin levels can occur as a physiological condition in females who are pregnant or lactating. As a pathological condition, hyperprolactinaemia is associated with gonadal dysfunction, infertility and an increased risk of long-term complications including osteoporosis. The most frequent cause of persistent hyperprolactinaemia is the presence of a micro- (<10mm diameter) or macroprolactinoma (>/=10mm). These pituitary tumours may produce an excessive amount of prolactin or disrupt the normal delivery of dopamine from the hypothalamus to the pituitary; prolactin secretion from the pituitary is inhibited by dopamine released from neurones in the hypothalamus. Medications including anti-psychotics can induce hyperprolactinaemia, while idiopathic hyperprolactinaemia accounts for 30-40% of cases. The prevalence of hyperprolactinaemia is difficult to establish as not all sufferers are symptomatic or concerned by their symptoms and may remain undiagnosed. Symptoms of hyperprolactinaemia include signs of hypogonadism, with oligomenorrhoea, amenorrhoea and galactorrhoea frequently observed. Pharmacological intervention should be considered the first line therapy and involves the use of dopamine agonists to reduce tumour size and prolactin levels. Bromocriptine has the longest history of use and is a well-established, inexpensive, safe and effective therapy option. However, bromocriptine requires multiple daily dosing and some patients are resistant or intolerant to this therapy. The two newer dopamine agonists, quinagolide and cabergoline, provide more effective and better tolerated treatments compared with bromocriptine and may offer effective therapies for bromocriptine-resistant or intolerant patients. Quinagolide can be used until pregnancy is confirmed and may result in improved compliance in females wishing to become pregnant. For patients with hyperprolactinaemia, pregnancy is safe and can frequently be beneficial, inducing a decrease in prolactin levels. There does not appear to be any increased risk of abortion, malformations or multiple births in pregnancies achieved with bromocriptine and this dopamine agonist can be used safely during pregnancy. Surgery should be considered only in certain circumstances, and for the majority of patients, dopamine agonists will be sufficient to alleviate symptoms and restore normal prolactin levels.     

Hyperprolactinemia.

Prolactinomas are the most common pituitary tumors. Hyperprolactinemia is characterized by increased production of prolactin, often leading to reproductive dysfunction and galactorrhea. Prolactinomas may also cause male-factor infertility by producing hypogonadism. In addition, if large, they can produce neurologic symptoms by mass effect in the sellar area. The diagnostic evaluation first requires exclusion of other causes of hyperprolactinemia, such as pregnancy, primary hypothyroidism, numerous medications, and miscellaneous causes. The second step in the diagnostic evaluation is to perform a head scan, preferably an MRI. This is essential in order to exclude a "pseudoprolactinoma" which would require surgery. Following diagnostic evaluation, the next step is to determine whether a patient with hyperprolactinemia has an indication for therapy, such as a macroprolactinoma (tumor >1 cm), hypogonadism (risk of osteoporosis), infertility, significant galactorrhea, acne, hirsutism, or headache. The treatment of choice for nearly all patients with hyperprolactinemic disorders is medical. In most cases, dopamine agonists (bromocriptine, pergolide, cabergoline) are extremely effective in lowering serum prolactin, restoring gonadal function, decreasing tumor size, and improving visual fields. The main limitation is side effects, particularly nausea or orthostatic dizziness. The newest dopamine agonist, cabergoline, can be given just once or twice a week, is more effective in normalizing prolactin and restoring menses than bromocriptine, and is significantly better tolerated. However, it is not yet recommended as first-line therapy for patients seeking fertility, because adequate safety data in pregnancy are not available. For the infrequent patient unable to tolerate, or resistant to, medical therapy, neurosurgical transsphenoidal resection may be necessary, particularly if the patient has a large lesion jeopardizing the optic chiasm. Hyperprolactinemia is a rewarding disorder to manage because patients typically respond well to medication, with restoration of menses and fertility.     

The Dilemma of Mild Hyperprolactinaemia

Summary: Ninety-eight women with mild hyperprolactinaemia (<4N) were followed for a mean duration of 5.5 years. Where pregnancy was desired treatment with bromocriptine (pM clomiphene) was effective in 87%. Following cessation of bromocriptine therapy almost one-third had a 'spontaneous' resolution of hyperprolactinaemia and resumed cyclical menstrual activity and fertility.
Pituitary tumours were identified on coned-view assessment in 9% of patients at the time of presentation and a further 10% during follow-up. Although some of these latter tumours may have been diagnosed earlier had CAT scans been performed routinely in all hyperprolactinaemic patients, such a policy would be hard to justify for those with mild hyperprolactinaemia as the tumours were small, produced no harmful effects, and would almost certainly have responded to bromocriptine should this have been administered.
All patients found to have pituitary tumours and given bromocriptine, showed no evidence of tumour progression subsequently, even where pregnancy occurred and the bromocriptine therapy was ceased. In addition, patients without pituitary tumours who were given bromocriptine to achieve pregnancy, were less likely to develop tumours during follow-up even when pregnancy had occurred.
Bromocriptine therapy can thus be justified in mildly hyperprolactinaemic patients to reduce troublesome galactorrhoea, achieve pregnancy, improve the chance of 'spontaneous' resolution of the menstrual problem and infertility, control or reduce tumour growth where a pituitary tumour has been identified, and reduce the risk of tumour development in patients with normal radiographs at the time of presentation.     

Macroprolactinomas with suprasellar extension: effect of bromocriptine withdrawal during one or more pregnancies.

OBJECTIVE: To investigate the effects of bromocriptine withdrawal during one or more pregnancies in patients who presented with pituitary macroprolactinomas with suprasellar extension. DESIGN: Four infertile patients presenting with a macroprolactinoma with suprasellar extension conceived during treatment with bromocriptine on 10 occasions resulting in eight full-term normal deliveries. Treatment was withheld shortly after conception in each pregnancy. RESULTS: Serum prolactin (PRL) levels fell initially from a mean of 2,776 (range 1,682 to 4,515) to 27 micrograms/L (range 1 to 71) with the development of a partially empty sella in all patients. Recovery of visual field defects occurred in the only affected individual. In case 1, PRL levels remained within the normal range, after bromocriptine withdrawal in the first pregnancy, with the development of an empty sella. Prolactin levels, however, increased substantially in cases 2 to 4. An asymptomatic suprasellar tumor extension returned in cases 2 and 3. After two or more pregnancies (cases 1, 3, and 4), there was a progressive decline in the serum PRL levels. Although still elevated in cases 3 and 4, the PRL levels were considerably below those obtained at presentation or in the first pregnancy. Tumor regression with the development of an empty sella was observed in both these patients as well in their pregnancy or postpartum period. CONCLUSIONS: Bromocriptine may be safely withdrawn during pregnancy in patients presenting with a macroprolactinoma. With multiple bromocriptine induced pregnancies, PRL levels and tumor size may progressively decrease with the eventual development of an empty sella.     

Long-term follow-up of 246 hyperprolactinemic patients

BACKGROUND: We wanted to evaluate the very long-term effects of bromocriptine on prolactin (PRL) levels and pituitary tumor size in a large cohort of hyperprolactinemic patients. METHODS: We conducted a retrospective cohort study in the Department of Endocrinology from Necker Hospital in Paris, France. Two hundred and forty-six patients consulted primarily for menstrual disorders, with diagnosis of hyperprolactinemia. Patients were followed-up for 99.9+/-3.6 months. One hundred and ninety-one were treated with bromocriptine, 32 underwent surgery, and 23 received no treatment. RESULTS: The mean initial plasma PRL level was 135.0+/-20.2 ng/ml. Presence of an adenoma was detected in 60% of our patients and comprised a microadenoma in 64% of cases. Compared to oligomenorrheic women, amenorrheic patients had significantly higher levels of PRL and larger pituitary tumor size. In the bromocriptine group, PRL levels decreased from 99.6+/-7.9 to 20.0+/-1.5 ng/ml (p=0.00001). The medical treatment was associated with disappearance of the adenoma in 45% of the women and with stabilization of pituitary tumor size in 40% of patients. Surgery led to disappearance of the adenoma in almost all cases, but failed to definitively cure hyperprolactinemia. CONCLUSION: In this large-scale retrospective study, the medical treatment of mild hyperprolactinemia was shown to be effective and sufficient after 9 years of follow-up.     

Chronic treatment with 2-alpha-bromocriptine in women with the hyperprolactinemic syndrome

Seventeen hyperprolactinemic patients with or without radiological evidences of a pituitary adenoma, were submitted to a long term (7-36 months) suppressive treatment with bromocriptine. Nine patients conceived during the treatment. All of them had a normal pregnancy and delivered normal babies. In all patients (with the exception of one-patient Z.S.) the post treatment prolactin levels were significantly lower than the pre-treatment values suggesting a long lasting suppressive effect of this dopamine agonist on the pituitary lactotrophs. Three of the patients followed throughout a whole menstrual cycle (3-10 months after discontinuation of therapy) showed presumptive signs of ovulation in spite of relatively elevated circulating immuno-reactive prolactin concentrations. These observations might suggest a modification of the biological activity of the hormone, possibly related to the chronic treatment with bromocriptine.     

Pregnancies in women with hyperprolactinaemia: obstetric and endocrinological management of 50 pregnancies in 37 women

Summary. Fifty pregnancies occurred in 37 women with hyperprolactinaemia. Thirty women (81%) initially attended with infertility and 24 (65%) had secondary amenorrhoea. Twelve women (31%) had pituitary macroadenomas, of whom seven (19%) were treated with neurosurgery and/or external radiotherapy before conception. Fortyone conceptions (82%) followed treatment with bromocriptine. There were no unusual obstetric or endocrinological complications. Scrum prolactin measured at least 6 months post partum when under basal conditions, without bromocriptine and not breast feeding, showed no significant trends compared with initial values. Tumour growth was not stimulated by the high oestrogen levels of pregnancy.