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Effects of long-term treatment with bromocriptine on pituitary prolactinoma in a male
Int. J. Gynaecol. Obstet., 1982, 20: 481-485 International Federation of Gynaecology & Obstetrics
EFFECTS OF LONG-TERM PROLACTINOMA IN A MALE
D. AYALON,
N. ECKSTEIN,
Z.T. HOMONNAIa,
Timsit Institute of Reproductive
Endocrinology,
for the Study of Fertility, and bDepartment (Received (Accepted
TREATMENT
G.F. PAZa,
WITH
A. ESHEL
BROMOCRIPTINE
ON
PITUITARY
and 1. REIDERb
Ichilov Hospital, 6 Weizmann Street, Tel Aviv 64239, Israel, aSoferman Institute
of Radiology, Municipal Governmental Medical Center, University of Tel Aviv, Israel
December 28th, 1981) March 15th, 1982)
Abstract
mia; Pituitary Hypogonadism;
Ayalon D, Eckstein N, Homonnai ZTa, Paz GFa, Eshel A, Reider I’=’(Timsit Institute of Reproductive Endocrinology, 6 Weizmann Street, Tel Aviv 64239, Israel, aSoferman Institute for the Study of Fertility, bDepartment of Radiology, the Municipal Governmental Medical Center, University of TelAviv, Israel. I Effects of long-term treatment with bromocriptine on pituitary prolactinoma in a male. Int J Gynaecol Obstet 20: 481-485,1982 Poor surgical results are obtained when operating on large prolactinomas, especially when an extrasellar growth is demonstrated. Several groups have reported tumor regression following bromocriptine treatment. A case report is presented of a young hyperprolactinemic man with a large pituitary adenoma with suprasellar extension, normal visual fields, decreased libido, impotence, hypogonadism and azoospermia. This man was treated with high doses of bromocriptine for a period of 5 months. A significant improvement of potency libido and sperm concentration associated with radiological evidence of a marked reduction of tumor size was noted following suppressive treatment with this ergot alkaloid.
Keywords:
Bromocriptine;
0020-7292/82/0000-0000/$02.75 0 1982 International Federation Printed and Published in Ireland
Hyperprolactine-
prolactinoma; Impotence
Azoospermia;
Introduction Prolactin secreting macroadenomas present a therapeutic challenge since the surgical cure rate diminishes with increasing tumor size [8,17]. Experience with radiotherapy is still limited and rarely are prolactin levels, fertility or gonadal function restored to normal, with this mode of therapy [ 191. Ergot derivatives are effective in inhibiting prolactin synthesis and release both in vivo and in vitro in experimental animals [4] and in pituitary cell culture [ 161. Their clinical use in the treatment of hyperprolactinemia has made a dramatic impact in this field of endocrinology. Many reports are now available on the use of bromocriptine in patients with hyperprolactinemia and show a rapid restoration of normal gonadal function with fall of prolactin concentration in the treated males and females [ 3,9]. In experimental animals ergot alkaloids have been shown to reduce the mitotic activity of pituitary cells in vivo [9,18]. But, although bromocriptine has been in use since 1971 for the treatment of patients with hyperprolactinemia (with or without obvious pituitary adenomas), only recently has evidence accumulated to suggest that it may Int J Gynaecol Obstet 20
of Cynaecology
& Obstetrics
482
Ayalon et al.
Fig. 1. Coronal CT head scan of patient F.R. before therapy showing a large enhancing mass in the pituitary fossa extending above the eroded sellar floor to a maximal height of 23 mm.
have an effect on tumor growth as well [ 1,2,6,7,10,13-15,20-221. These results prompted us to treat conservatively with bromocriptine a young hyperprolactinemic man with a huge pituitary adenoma who suffered from decreased libido, impotence, and azoospermia and whose chief complaint was infertility. Case report F.R., aged 31 years, was admitted to our outpatient clinic for complaints of decreased libido and potency, and primary infertility. There was no past history of visual blurring or headaches. Puberty had commenced at 14 years but Table I.
the patient had not attained normal beard growth or normal libido and had experienced only rare morning Physical erections. examination revealed a 175~cm, SO-kg man who appeared younger than his chronological age. There was sparce facial and body hair, normal testicular size and no gynecomastia or galactorrhea. Visual field and fundal examination were normal with normal acuity. Conventional tomography demonstrated destruction of the anterior and posterior clinoids and of erosion of the Alar floor. Computerized tomographic (CT) scan of the head confirmed, on a coronal section, the presence of an enhancing intrasellar mass extending inferiorly in the sphenoid sinus with a maximal height of 23 mm (Fig. 1). The
Results of LRH-TRH stimulation test before treatment.
Time
LH
FSH
hPRL
TSH
(nslml)
(ns/ml)
(n&-N
T,
T,
(min)
(mIU/d)
h/W
olg/w
51 148 138
101 120 159
886 123 851
3 10 5
159 157
0
30 120
ZntJ Gynaecol Obstet 20
9 _
Bromocriptine
0
2
4
6
6 Time
Fig, 2.
IO
12
14
16
18
483
20
(weeks)
Fluctuation of serum hPRL and plasma testosterone
concentrations
Semen analyses throughout treatment with bromocriptine: Sperm Cont. (IO/ml)
under bromocriptme
treatment
increased to 10 mgjday and under this treatment, undetectable prolactin levels (<2.5 ng/ ml) were noted on the ninth week of treatment. An additional daily dose of 5 mg bromocriptine was added thereafter in order to achieve an effective suppression of the tumorous process. The decrease in prolactin levels was associated with a rise of testosterone concentration reaching normal male concentration (5 ng/ml) 3 weeks after the start of the treatment (Fig. 2). Within 5 weeks of therapy there was a and remarkable improvement in libido potency. Two months after bromocriptine therapy was begun, the patient was asympto matic. Within 3 months of treatment, a
laboratory data are summarized in Table I. Basal gonadotropin levels were low with a normal response to LRH stimulation. Basal prolactin levels were elevated (886 ng/ml: normal <20 ng/ml) with a paradoxical suppression of prolactin levels following TRH stimulation. Thyroid function was normal. The serum testosterone level was 2 ng/ml (normal male range, 4-10 ng/ml). The semen analysis was remarkable for the very small volume (0.3 ml) associated with azoospermia. Treatment was started with an initial daily dose of 2.5 mg bromocriptine and the patient’s prolactin serum levels fell by 90% within 1 week to 85 ng/ml. Within 3 weeks, the dose of bromocriptine was gradually Table II.
and pituitary prolactinomas
Motility (% after 1 h)
duration of bromocriptine
Bromocriptine (&day)
hPRL (ng/mU
Seminal Vol. W)
_ 2.5 10.0
886 88 <2.5
0.3 0.3 0.3
0 0 0
_ _ _
_ _ _
15.0 15.0 15.0
<2.5 <2.5 <2.5
3.0 2.5 2.0
236 162 95
35 50 60
70 80 80
treatment:
5 months.
Morphology t% normal)
Int J Gvnaecof Ohstet _‘O
484
Ayalon et al.
Fig. 3. Coronal CT head scan of patient F.R. Top panel: 3 months after starting bromocriptine therapy the scan shows reduction of tumor size to a suprasellar extension of 19 mm. Lower panel: 6 months after starting bromocriptine therapy further reduction of tumor size (suprasellar extension of 13 mm).
significant increase of the seminal volume as well as a normal sperm count, normal motility and sperm morphology were noted (Table II). After 6 months of therapy his wife conceived. A C.T. scan performed 3 months after commencement of therapy revealed reduction of tumor size to 19 mm height. A further regression of the tumor was noted 6 months after the start of bromocriptine therapy from a height of 23 mm before treatment to 13 mm (Fig. 3). Discussion In experimental animals dopamine agonists, including bromocriptine, have been shown to Int J Gynaecol Obstet 20
reduce the mitotic activity of pituitary cells stimulated by estrogen in vivo [ 11,12,18]. Since 1975 these observations have been applied to patients with pituitary tumors. In 1979 McGregor presented radiographic evidence that bromocriptine is effective in reducing the volume of some prolactinsecreting pituitary adenomas [ 141. Thorner has also recently reported a rapid tumor regression in two patients on a low dosage of bromocriptine [ 2 11, The rationale for the medical approach to therapy was based on the poor surgical results in patients with large prolactinomas. Hardy reported a 40-50% cure rate in patients with macroadenomas and only 19% cure when the prolactin levels were higher than 500 ng/ml [ 181. In addition, the probability of postoperative permanent hypopituitarism increases with the size of the tumor [5,8,17]. Certain prolactinomas are so advanced that the only alternative to bromocriptine therapy is a complete hypophysectomy - clearly a rather drastic solution for one whose chief complaint is infertility. The results obtained in our patient are in agreement with the preliminary reports that suggest that bromocriptine may have a beneficial effect in reducing tumor size. The final role of bromocriptine as primary treatment for large or small prolactinomas is unclear. The long-term side effects of this expensive drug are yet unknown and its effect in controlling tumors may conceivably diminish with long-term therapy. The basal problem which remains to be solved is whether the optimal treatment is medical, to shrink the tumor followed by surgery, or is it surgery or medical treatment alone. References Be& T, Bergstrom K, Larsson SG, Lundberg PO, Nillius SJ, Wide L: Bromocriptine-induced tumour regression in two women with prolactin-secreting pituitary tumours. Acta Endocr (Kbh) 91, Suppl. 225: 180,1979. Corenblum B: Bromocriptme in pituitary tumors. Lancet 2: 786, 1978. Del Pozo E, Varga E, Wyss H, Tolis G, Friesen H,
Bromocriptine and pituitary prohctinomus
4
5
6
7
8
9
10
11
12
13
14
Wemmer R, Velter L, Vettwiller A: Clinical and hormc+ nal response to bromocriptine in the galactorrhea syndromes. J Clin Endocrinol Metab 39: 18, 1974. Fluckiger E, Wagner H: 2-&+ergokryptine: beeinflussung von fertilitat und laktation bei der ratte. Experientia 24: 1130, 1968. Franks S, Jacobs HS, Hall MGR, Steele SJ, Nabarro JDN: Management of hyperprolactinemic amenorrhea. Br J Obstet Gynaecol84: 241, 1977. George SR, Burrow GN, Zinman B, Ezrin C: Regression of pituitary tumors, a possible effect of bromocriptine. Am J Med 66: 697, 1979. Gonzalez ER: Update: pituitary tumor regression with bromocriptine therapy. JAMA (Medical News) 244: 1535, 1980. Hardy J, Beauregard H, Robert F: Prolactin-secreting pituitary adenomas: transsphenoidal microsurgical treatment. In Progress in Prolactin Physiology and Pathology (ed C Robyn, M Harter), p 361. Elsevier/North-Holland, New York, 1978. Kleinberg DL, Gordon LN, Frantz AG: Galactorrhea: A study of 235 cases including 48 with pituitary tumors. N Engl J Med 296: 589, 1977. Landolt AM, Wuthrich R, Felhnann H: Regression of pituitary prolactinoma after treatment with bromocriptine. Lancet 1: 1082, 1979. Lloyd NH, Meares JD, Jacobi J: Effects of estrogens and bromocriptine on in vivo secretion and mitosis in pr* lactin cell. Nature 255: 497, 1975. MacLeod RM, Lehmeyer JE: Suppression of pituitary tumour growth and function by ergot alkaloids. Cancer Res 33: 849, 1973. McGregor AM, Scanlon MF, Hall K, Cook DB, Hall R: Reduction in size of a pituitary tumor by bromocriptine therapy. N EngJ J Med 300: 291, 1979. McGregor AM, Scanlon MF, Hall R, Hall K: Effects of bromocriptine on pituitary tumour size. Br Med J 2: 700,1979.
485
15 Miihlenstedt D, Osmers F, Schneider HPG: Tumour regression in pituitary adenoma by bromocriptine. Arch Gynecol2.26: 341,1978. la Pasteels JL, Danguy A, Frerotte M, Ectors F: Inhibition de la s&r&ion de pro&tine par l’ergocomine et la 2-&+ergokriptine: action dire&e sur l’hypophyse en culture. Ann Endocrinol Paris) 32: 188, 1971. 17 Post KD, Biller BJ, Adelman LS, Wolpert ME, Reichlin S: Selective transsphenoidal adenomectomy in woman with galactorrhea-amenorrhea. JAMA 242: 158, 1979. 18 Quadri SK, Lu KM, Meites J: Ergot-induced inhibition of pituitary tumour growth in rats. Science 176: 417, 1972. 19 Reyes FI, Gomez C, Faimar C: Pathological hyperpre lactinemia: A five year experience. In Prolactin and Human Reproduction (eds PG Crosignani, C Robyn), p 259. Academic Press, London, 1977. 20 Sobrinho LG, Nunes MCP, Santos MA, Mauricio JC: Radiological evidence for regression of prolactinoma and treatment with bromocriptine. Lancet 2: 257,1978. 21 Thorner MO, Martin WH, Rogol AD, Morris JL, Perryman RL, Conway BP, Howards SS, Wolfmann MG, MacLeod RM: Rapid regression of pituitary prolactinomas during bromocriptine treatment. J Clin Endocrinol Metab 51: 438, 1980. 22 Wass JAH, Moult PJA, Thorner MO, Dacie JE, Charlesworth M, Jones AE, Besser GM: Reduction of pituitarytumour size in patient with prolactinomas and acre megaly treated with bromocriptine with or without radiotherapy. Lancet 2: 66, 1979. Address for reprints: Daniel Ayalon, M.D. Timsit Institute of Reproductive Endocrinology, khilov Hospital, 6, Weizmann Street, Tel Aviv 64 239, Israel
Int J Gynaecol Obstet 20
EFFECTS OF LONG-TERM PROLACTINOMA IN A MALE
D. AYALON,
N. ECKSTEIN,
Z.T. HOMONNAIa,
Timsit Institute of Reproductive
Endocrinology,
for the Study of Fertility, and bDepartment (Received (Accepted
TREATMENT
G.F. PAZa,
WITH
A. ESHEL
BROMOCRIPTINE
ON
PITUITARY
and 1. REIDERb
Ichilov Hospital, 6 Weizmann Street, Tel Aviv 64239, Israel, aSoferman Institute
of Radiology, Municipal Governmental Medical Center, University of Tel Aviv, Israel
December 28th, 1981) March 15th, 1982)
Abstract
mia; Pituitary Hypogonadism;
Ayalon D, Eckstein N, Homonnai ZTa, Paz GFa, Eshel A, Reider I’=’(Timsit Institute of Reproductive Endocrinology, 6 Weizmann Street, Tel Aviv 64239, Israel, aSoferman Institute for the Study of Fertility, bDepartment of Radiology, the Municipal Governmental Medical Center, University of TelAviv, Israel. I Effects of long-term treatment with bromocriptine on pituitary prolactinoma in a male. Int J Gynaecol Obstet 20: 481-485,1982 Poor surgical results are obtained when operating on large prolactinomas, especially when an extrasellar growth is demonstrated. Several groups have reported tumor regression following bromocriptine treatment. A case report is presented of a young hyperprolactinemic man with a large pituitary adenoma with suprasellar extension, normal visual fields, decreased libido, impotence, hypogonadism and azoospermia. This man was treated with high doses of bromocriptine for a period of 5 months. A significant improvement of potency libido and sperm concentration associated with radiological evidence of a marked reduction of tumor size was noted following suppressive treatment with this ergot alkaloid.
Keywords:
Bromocriptine;
0020-7292/82/0000-0000/$02.75 0 1982 International Federation Printed and Published in Ireland
Hyperprolactine-
prolactinoma; Impotence
Azoospermia;
Introduction Prolactin secreting macroadenomas present a therapeutic challenge since the surgical cure rate diminishes with increasing tumor size [8,17]. Experience with radiotherapy is still limited and rarely are prolactin levels, fertility or gonadal function restored to normal, with this mode of therapy [ 191. Ergot derivatives are effective in inhibiting prolactin synthesis and release both in vivo and in vitro in experimental animals [4] and in pituitary cell culture [ 161. Their clinical use in the treatment of hyperprolactinemia has made a dramatic impact in this field of endocrinology. Many reports are now available on the use of bromocriptine in patients with hyperprolactinemia and show a rapid restoration of normal gonadal function with fall of prolactin concentration in the treated males and females [ 3,9]. In experimental animals ergot alkaloids have been shown to reduce the mitotic activity of pituitary cells in vivo [9,18]. But, although bromocriptine has been in use since 1971 for the treatment of patients with hyperprolactinemia (with or without obvious pituitary adenomas), only recently has evidence accumulated to suggest that it may Int J Gynaecol Obstet 20
of Cynaecology
& Obstetrics
482
Ayalon et al.
Fig. 1. Coronal CT head scan of patient F.R. before therapy showing a large enhancing mass in the pituitary fossa extending above the eroded sellar floor to a maximal height of 23 mm.
have an effect on tumor growth as well [ 1,2,6,7,10,13-15,20-221. These results prompted us to treat conservatively with bromocriptine a young hyperprolactinemic man with a huge pituitary adenoma who suffered from decreased libido, impotence, and azoospermia and whose chief complaint was infertility. Case report F.R., aged 31 years, was admitted to our outpatient clinic for complaints of decreased libido and potency, and primary infertility. There was no past history of visual blurring or headaches. Puberty had commenced at 14 years but Table I.
the patient had not attained normal beard growth or normal libido and had experienced only rare morning Physical erections. examination revealed a 175~cm, SO-kg man who appeared younger than his chronological age. There was sparce facial and body hair, normal testicular size and no gynecomastia or galactorrhea. Visual field and fundal examination were normal with normal acuity. Conventional tomography demonstrated destruction of the anterior and posterior clinoids and of erosion of the Alar floor. Computerized tomographic (CT) scan of the head confirmed, on a coronal section, the presence of an enhancing intrasellar mass extending inferiorly in the sphenoid sinus with a maximal height of 23 mm (Fig. 1). The
Results of LRH-TRH stimulation test before treatment.
Time
LH
FSH
hPRL
TSH
(nslml)
(ns/ml)
(n&-N
T,
T,
(min)
(mIU/d)
h/W
olg/w
51 148 138
101 120 159
886 123 851
3 10 5
159 157
0
30 120
ZntJ Gynaecol Obstet 20
9 _
Bromocriptine
0
2
4
6
6 Time
Fig, 2.
IO
12
14
16
18
483
20
(weeks)
Fluctuation of serum hPRL and plasma testosterone
concentrations
Semen analyses throughout treatment with bromocriptine: Sperm Cont. (IO/ml)
under bromocriptme
treatment
increased to 10 mgjday and under this treatment, undetectable prolactin levels (<2.5 ng/ ml) were noted on the ninth week of treatment. An additional daily dose of 5 mg bromocriptine was added thereafter in order to achieve an effective suppression of the tumorous process. The decrease in prolactin levels was associated with a rise of testosterone concentration reaching normal male concentration (5 ng/ml) 3 weeks after the start of the treatment (Fig. 2). Within 5 weeks of therapy there was a and remarkable improvement in libido potency. Two months after bromocriptine therapy was begun, the patient was asympto matic. Within 3 months of treatment, a
laboratory data are summarized in Table I. Basal gonadotropin levels were low with a normal response to LRH stimulation. Basal prolactin levels were elevated (886 ng/ml: normal <20 ng/ml) with a paradoxical suppression of prolactin levels following TRH stimulation. Thyroid function was normal. The serum testosterone level was 2 ng/ml (normal male range, 4-10 ng/ml). The semen analysis was remarkable for the very small volume (0.3 ml) associated with azoospermia. Treatment was started with an initial daily dose of 2.5 mg bromocriptine and the patient’s prolactin serum levels fell by 90% within 1 week to 85 ng/ml. Within 3 weeks, the dose of bromocriptine was gradually Table II.
and pituitary prolactinomas
Motility (% after 1 h)
duration of bromocriptine
Bromocriptine (&day)
hPRL (ng/mU
Seminal Vol. W)
_ 2.5 10.0
886 88 <2.5
0.3 0.3 0.3
0 0 0
_ _ _
_ _ _
15.0 15.0 15.0
<2.5 <2.5 <2.5
3.0 2.5 2.0
236 162 95
35 50 60
70 80 80
treatment:
5 months.
Morphology t% normal)
Int J Gvnaecof Ohstet _‘O
484
Ayalon et al.
Fig. 3. Coronal CT head scan of patient F.R. Top panel: 3 months after starting bromocriptine therapy the scan shows reduction of tumor size to a suprasellar extension of 19 mm. Lower panel: 6 months after starting bromocriptine therapy further reduction of tumor size (suprasellar extension of 13 mm).
significant increase of the seminal volume as well as a normal sperm count, normal motility and sperm morphology were noted (Table II). After 6 months of therapy his wife conceived. A C.T. scan performed 3 months after commencement of therapy revealed reduction of tumor size to 19 mm height. A further regression of the tumor was noted 6 months after the start of bromocriptine therapy from a height of 23 mm before treatment to 13 mm (Fig. 3). Discussion In experimental animals dopamine agonists, including bromocriptine, have been shown to Int J Gynaecol Obstet 20
reduce the mitotic activity of pituitary cells stimulated by estrogen in vivo [ 11,12,18]. Since 1975 these observations have been applied to patients with pituitary tumors. In 1979 McGregor presented radiographic evidence that bromocriptine is effective in reducing the volume of some prolactinsecreting pituitary adenomas [ 141. Thorner has also recently reported a rapid tumor regression in two patients on a low dosage of bromocriptine [ 2 11, The rationale for the medical approach to therapy was based on the poor surgical results in patients with large prolactinomas. Hardy reported a 40-50% cure rate in patients with macroadenomas and only 19% cure when the prolactin levels were higher than 500 ng/ml [ 181. In addition, the probability of postoperative permanent hypopituitarism increases with the size of the tumor [5,8,17]. Certain prolactinomas are so advanced that the only alternative to bromocriptine therapy is a complete hypophysectomy - clearly a rather drastic solution for one whose chief complaint is infertility. The results obtained in our patient are in agreement with the preliminary reports that suggest that bromocriptine may have a beneficial effect in reducing tumor size. The final role of bromocriptine as primary treatment for large or small prolactinomas is unclear. The long-term side effects of this expensive drug are yet unknown and its effect in controlling tumors may conceivably diminish with long-term therapy. The basal problem which remains to be solved is whether the optimal treatment is medical, to shrink the tumor followed by surgery, or is it surgery or medical treatment alone. References Be& T, Bergstrom K, Larsson SG, Lundberg PO, Nillius SJ, Wide L: Bromocriptine-induced tumour regression in two women with prolactin-secreting pituitary tumours. Acta Endocr (Kbh) 91, Suppl. 225: 180,1979. Corenblum B: Bromocriptme in pituitary tumors. Lancet 2: 786, 1978. Del Pozo E, Varga E, Wyss H, Tolis G, Friesen H,
Bromocriptine and pituitary prohctinomus
4
5
6
7
8
9
10
11
12
13
14
Wemmer R, Velter L, Vettwiller A: Clinical and hormc+ nal response to bromocriptine in the galactorrhea syndromes. J Clin Endocrinol Metab 39: 18, 1974. Fluckiger E, Wagner H: 2-&+ergokryptine: beeinflussung von fertilitat und laktation bei der ratte. Experientia 24: 1130, 1968. Franks S, Jacobs HS, Hall MGR, Steele SJ, Nabarro JDN: Management of hyperprolactinemic amenorrhea. Br J Obstet Gynaecol84: 241, 1977. George SR, Burrow GN, Zinman B, Ezrin C: Regression of pituitary tumors, a possible effect of bromocriptine. Am J Med 66: 697, 1979. Gonzalez ER: Update: pituitary tumor regression with bromocriptine therapy. JAMA (Medical News) 244: 1535, 1980. Hardy J, Beauregard H, Robert F: Prolactin-secreting pituitary adenomas: transsphenoidal microsurgical treatment. In Progress in Prolactin Physiology and Pathology (ed C Robyn, M Harter), p 361. Elsevier/North-Holland, New York, 1978. Kleinberg DL, Gordon LN, Frantz AG: Galactorrhea: A study of 235 cases including 48 with pituitary tumors. N Engl J Med 296: 589, 1977. Landolt AM, Wuthrich R, Felhnann H: Regression of pituitary prolactinoma after treatment with bromocriptine. Lancet 1: 1082, 1979. Lloyd NH, Meares JD, Jacobi J: Effects of estrogens and bromocriptine on in vivo secretion and mitosis in pr* lactin cell. Nature 255: 497, 1975. MacLeod RM, Lehmeyer JE: Suppression of pituitary tumour growth and function by ergot alkaloids. Cancer Res 33: 849, 1973. McGregor AM, Scanlon MF, Hall K, Cook DB, Hall R: Reduction in size of a pituitary tumor by bromocriptine therapy. N EngJ J Med 300: 291, 1979. McGregor AM, Scanlon MF, Hall R, Hall K: Effects of bromocriptine on pituitary tumour size. Br Med J 2: 700,1979.
485
15 Miihlenstedt D, Osmers F, Schneider HPG: Tumour regression in pituitary adenoma by bromocriptine. Arch Gynecol2.26: 341,1978. la Pasteels JL, Danguy A, Frerotte M, Ectors F: Inhibition de la s&r&ion de pro&tine par l’ergocomine et la 2-&+ergokriptine: action dire&e sur l’hypophyse en culture. Ann Endocrinol Paris) 32: 188, 1971. 17 Post KD, Biller BJ, Adelman LS, Wolpert ME, Reichlin S: Selective transsphenoidal adenomectomy in woman with galactorrhea-amenorrhea. JAMA 242: 158, 1979. 18 Quadri SK, Lu KM, Meites J: Ergot-induced inhibition of pituitary tumour growth in rats. Science 176: 417, 1972. 19 Reyes FI, Gomez C, Faimar C: Pathological hyperpre lactinemia: A five year experience. In Prolactin and Human Reproduction (eds PG Crosignani, C Robyn), p 259. Academic Press, London, 1977. 20 Sobrinho LG, Nunes MCP, Santos MA, Mauricio JC: Radiological evidence for regression of prolactinoma and treatment with bromocriptine. Lancet 2: 257,1978. 21 Thorner MO, Martin WH, Rogol AD, Morris JL, Perryman RL, Conway BP, Howards SS, Wolfmann MG, MacLeod RM: Rapid regression of pituitary prolactinomas during bromocriptine treatment. J Clin Endocrinol Metab 51: 438, 1980. 22 Wass JAH, Moult PJA, Thorner MO, Dacie JE, Charlesworth M, Jones AE, Besser GM: Reduction of pituitarytumour size in patient with prolactinomas and acre megaly treated with bromocriptine with or without radiotherapy. Lancet 2: 66, 1979. Address for reprints: Daniel Ayalon, M.D. Timsit Institute of Reproductive Endocrinology, khilov Hospital, 6, Weizmann Street, Tel Aviv 64 239, Israel
Int J Gynaecol Obstet 20