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Tomokatsu Hori - One of the best experts on this subject based on the ideXlab platform.
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individualized high dose cabergoline therapy for hyperprolactinemic infertility in women with micro and macroprolactinomas
Obstetrical & Gynecological Survey, 2010Co-Authors: Masami Ono, Nobuhiro Miki, Kosaku Amano, Takakazu Kawamata, Toshiro Seki, Rena Makino, Kazue Takano, Shunichiro Izumi, Yoshikazu Okada, Tomokatsu HoriAbstract:The dopamine receptor agonist, bromocriptine, has been first-line treatment for hyperprolactinemic infertility in young women of reproductive age with pituitary hormone-producing adenomas for the past 30 years. Several studies have shown that cabergoline has superior efficacy and tolerability, and in recent years, it has replaced bromocriptine as the first-choice dopamine agonist in this population. In women with hyperprolactinemic amenorrhea, cabergoline corrects Hyperprolactinemia and is more effective than bromocriptine in achieving recovery of the ovulatory cycle. Although cabergoline can induce pregnancy in prolactinoma patients, the rate of pregnancy induction in these women is unknown. In patients with macroprolactinomas (macroadenomas), its effectiveness for controlling tumor growth and thereby inducing successful pregnancy is also unknown. The aim of this study was to determine the efficacy and safety of cabergoline in pregnancy induction and its outcomes in infertile women with prolactinomas. Between 2001 and 2005, the participants—85 infertile women with macroprolactinomas (n = 29) or microprolactinomas (n = 56)—received prospective, high-dose cabergoline therapy for suppression of prolactin and tumor shrinkage. Of the 85 subjects, 31 were bromocriptine resistant, 32 were bromocriptine intolerant, and 22 were newly diagnosed untreated patients. Conception was withheld in patients with microadenomas or macroadenomas until 3 regular menstrual cycles returned and in women with macroadenomas until tumors shrunk to less than 1 cm in height. The drug was withdrawn at the fourth gestational week. Cabergoline corrected and normalized Hyperprolactinemia, increased serum progesterone levels and achieved recovery of the ovulatory cycle in all patients. Within 6 to 24 months after the initiation of cabergoline therapy, all tumors contracted, and 11 of the 29 macroadenomas and 29 of the 56 microadenomas disappeared. Of the 85 patients, 80 (94%) conceived 95 pregnancies; 2 of the 95 were second pregnancies conceived without use of cabergoline. The drug dose at the first pregnancy varied widely (0.25-9 mg/week overall and 2-9 mg/week in bromocriptine-resistant patients). Of the 93 pregnancies induced with cabergoline, 86 resulted in 83 single live births, 1 stillbirth, and 2 abortions (1 of which was spontaneous); the remaining 7 pregnancies were ongoing. All newborns were healthy, without malformations or abnormal development. None of the mothers experienced impaired vision or headache suggestive of abnormal macroprolactinoma re-expansion during pregnancy. These findings show that cabergoline can safely induce and promote successful pregnancy in most infertile women with prolactinoma, independent of tumor size or bromocriptine resistance and intolerance. Cabergoline monotherapy has the potential to substitute for the conventional combination therapy of surgery or radiotherapy plus bromocriptine in patients with macroadenomas.
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individualized high dose cabergoline therapy for hyperprolactinemic infertility in women with micro and macroprolactinomas
The Journal of Clinical Endocrinology and Metabolism, 2010Co-Authors: Masami Ono, Nobuhiro Miki, Kosaku Amano, Takakazu Kawamata, Toshiro Seki, Rena Makino, Kazue Takano, Shunichiro Izumi, Yoshikazu Okada, Tomokatsu HoriAbstract:Context: Cabergoline is effective for hyperprolactinemic hypogonadism. However, the rate of cabergoline-induced pregnancy in women with prolactinoma remains unknown. Also unknown is whether cabergoline can control tumor growth and thereby achieve successful pregnancy in patients with macroprolactinomas. Methods: Eighty-five women with macroprolactinomas (n = 29) or microprolactinomas (n = 56) received prospective, high-dose cabergoline therapy for infertility based on individual prolactin suppression and/or tumor shrinkage. The patients included 31 bromocriptine-resistant, 32 bromocriptine-intolerant, and 22 previously untreated women. Conception was withheld until three regular cycles returned in women with microadenoma and until tumors shrank below 1.0 cm in height in women with macroadenoma. Cabergoline was withdrawn at the fourth gestational week. Results: Cabergoline normalized Hyperprolactinemia and recovered the ovulatory cycle in all patients. All adenomas contracted, and 11 macroadenomas and 29 m...
M F Scanlon - One of the best experts on this subject based on the ideXlab platform.
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long term remission following withdrawal of dopamine agonist therapy in subjects with microprolactinomas
Obstetrical & Gynecological Survey, 2005Co-Authors: M Biswas, J Smith, Deepak R Jadon, P Mcewan, Dafydd Aled Rees, L M Evans, M F Scanlon, J S DaviesAbstract:Although two thirds or more of patients with microprolactinoma achieve normal serum prolactin levels over the long term after withdrawal of dopamine agonist therapy, there is no agreement on the appropriate duration of treatment, and treatment is not always interrupted. In this retrospective analysis of 89 patients, 84 women and 5 men with a mean age of 33 years, remissions were analyzed in 67 patients treated with 0.5 to 3 mg cabergoline weekly and 22 others given 2.5 to 10 mg bromocriptine daily. The mean duration of therapy was 3.1 years, and patients were followed for at least 1 year after treatment ended. None of the patients received medication other than a dopamine agonist. Seven women discontinued treatment when they became pregnant. All patients were symptomatic and hyperprolactinemic when first seen. Among 57 patients (64%) who had a recurrence after treatment stopped were 46 (81%) who had recurrent symptomatic Hyperprolactinemia within 12 months after stopping treatment. The average interval was 9.6 months. Thirty-two patients, 36% of the total, achieved remission after at least 1 year of follow up; the mean duration of remission was 3.6 years. Nearly 85% of these patients remained in remission for longer than 2 years. Four of them were asymptomatic despite being hyperprolactinemic. The 2 dopamine agonists were equally effective. The overall median duration before relapse after discontinuance of treatment was 12 months. Logistic regression analysis failed to demonstrate an association between the risk of recurrence and age at presentation, imaging of an adenoma, or the duration of treatment. When dopamine agonist therapy is abruptly withdrawn after 2 years or longer in patients with microprolactinoma, 30% to 40% achieve long-term remission without side effects. Because symptomatic Hyperprolactinemia may develop more than 1 year after treatment stops, long-term follow up is essential.
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a comparison of cabergoline and bromocriptine in the treatment of hyperprolactinemic amenorrhea
The New England Journal of Medicine, 1994Co-Authors: Jonathan Webster, Gabriella Piscitelli, A Polli, Carlo Ferrari, Ikram Shah Bin Ismail, M F ScanlonAbstract:Background Cabergoline is a long-acting dopamine-agonist drug that suppresses prolactin secretion and restores gonadal function in women with hyperprolactinemic amenorrhea. We designed a study to compare its safety and efficacy with those of bromocriptine, which has been the standard therapy. Methods A total of 459 women with hyperprolactinemic amenorrhea were treated with either cabergoline (0.5 to 1.0 mg twice weekly) or bromocriptine (2.5 to 5.0 mg twice daily), administered in a double-blind fashion for 8 weeks and subsequently in an open fashion for 16 weeks, during which adjustments in the dose were made according to the response. Of the 459 women, 279 had microprolactinomas, 3 had macroprolactinomas, 1 had a craniopharyngioma, 167 had idiopathic Hyperprolactinemia, and the remainder had an empty sella. Clinical and biochemical status was assessed at 2-week intervals for 8 weeks and monthly thereafter for a total of 6 months, with an additional assessment at 14 weeks. Results Stable normoprolactinem...
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a comparison of cabergoline and bromocriptine in the treatment of hyperprolactinemic amenorrhea
The New England Journal of Medicine, 1994Co-Authors: J Webster, Gabriella Piscitelli, A Polli, Carlo Ferrari, Ikram Shah Bin Ismail, M F ScanlonAbstract:BACKGROUND: Cabergoline is a long-acting dopamine-agonist drug that suppresses prolactin secretion and restores gonadal function in women with hyperprolactinemic amenorrhea. We designed a study to compare its safety and efficacy with those of bromocriptine, which has been the standard therapy. METHODS: A total of 459 women with hyperprolactinemic amenorrhea were treated with either cabergoline (0.5 to 1.0 mg twice weekly) or bromocriptine (2.5 to 5.0 mg twice daily), administered in a double-blind fashion for 8 weeks and subsequently in an open fashion for 16 weeks, during which adjustments in the dose were made according to the response. Of the 459 women, 279 had microprolactinomas, 3 had macroprolactinomas, 1 had a craniopharyngioma, 167 had idiopathic Hyperprolactinemia, and the remainder had an empty sella. Clinical and biochemical status was assessed at 2-week intervals for 8 weeks and monthly thereafter for a total of 6 months, with an additional assessment at 14 weeks. RESULTS: Stable normoprolactinemia was achieved in 186 of the 223 women treated with cabergoline (83 percent) and 138 of the 236 women treated with bromocriptine (59 percent, P < 0.001). Seventy-two percent of the women treated with cabergoline and 52 percent of those treated with bromocriptine had ovulatory cycles or became pregnant during treatment (P < 0.001). Amenorrhea persisted in 7 percent of the cabergoline-treated women and 16 percent of the bromocriptine-treated women. Adverse effects were recorded in 68 percent of the women taking cabergoline and 78 percent of those taking bromocriptine (P = 0.03); 3 percent discontinued taking cabergoline, and 12 percent stopped taking bromocriptine (P < 0.001) because of drug intolerance. Gastrointestinal symptoms were significantly less frequent, less severe, and shorter-lived in the women treated with cabergoline. CONCLUSIONS: Cabergoline is more effective and better tolerated than bromocriptine in women with hyperprolactinemic amenorrhea.
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dopamine agonists and pituitary tumor shrinkage
Endocrine Reviews, 1992Co-Authors: John S Bevan, Jonathan Webster, Christopher W Burke, M F ScanlonAbstract:The primary aim of this review has been to clarify the tumor shrinking effects of dopamine agonists on pituitary macroadenomas of different cell types. Shrinkage is most dramatic for macroprolactinomas and is due to cell size reduction. Seventy-nine percent of 271 definite macroprolactinomas were reduced in size by at least 25%, and 89% shrank to some degree. Most shrinkage occurs during the first 3 months of treatment, although in a minority shrinkage is delayed. Dopamine agonist resistance during long-term therapy is exceptional. Drug withdrawal nearly always leads to a return of Hyperprolactinemia, even after several years treatment, although early tumor reexpansion is unusual. About 10% of true macroprolactinomas do not shrink with dopamine agonists; the molecular mechanisms of such resistance have yet to be determined. Alternative formulations of BC and new dopamine agonists (CV 205-502 and cabergoline) are useful for the minority of patients unable to tolerate oral BC, but do not seem to further improve overall shrinkage rates. The risks of pregnancy have probably been overstated, and BC is suitable primary treatment for women with prolactinomas of all sizes; the drug can be used safely during pregnancy in the event of clinically relevant tumor expansion. The interpretation of different degrees of Hyperprolactinemia is discussed and management strategies suggested. Most patients with macroprolactinomas now avoid surgery, but drug-induced, time-dependent tumor fibrosis should be remembered if surgery is contemplated. Nonfunctioning pituitary tumors are mostly of gonadotroph cell origin and may be associated with significant disconnection hyperprolactinaemia. Seventy-six of 84 well-characterized tumors showed no tumor shrinkage during dopamine agonist therapy. Possible explanations include abnormalities of dopamine receptor number and function. Preliminary evidence suggests that dopamine agonists may restrain the growth of some functionless tumors; most of these tumors, however, can be satisfactorily debulked using transsphenoidal surgery. In contrast to macroprolactinomas, other functioning pituitary tumors (GH-, TSH-, and ACTH-secreting) rarely shrink during dopamine agonist therapy, although the number of tumors studied is small.
Janine L Brown - One of the best experts on this subject based on the ideXlab platform.
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hyperprolactinemic african elephant loxodonta africana females exhibit elevated dopamine oxytocin and serotonin concentrations compared to normal cycling and noncycling low prolactin elephants
Biology of Reproduction, 2019Co-Authors: Natalia A Prado, Mia Keady, Alexa Oestmann, Cathleen M Steinbeiser, Janine L BrownAbstract:Many zoo elephants do not cycle normally, and for African elephants, it is often associated with Hyperprolactinemia. Dopamine agonists successfully treat Hyperprolactinemia-induced ovarian dysfunction in women, but not elephants. The objective of this study was to determine how longitudinal dopamine, serotonin, and oxytocin patterns in African elephants are related to ovarian cycle function. We hypothesized that dopamine concentrations are decreased, while oxytocin and serotonin are increased in non-cycling, hyperprolactinemic African elephants. Weekly urine and serum samples were collected for eight consecutive months from 28 female African elephants. Females were categorized as follows: (1) non-cycling with average prolactin concentrations of 15 ng/ml or greater (HIGH; n = 7); (2) non-cycling with average prolactin concentrations below 15 ng/ml (LOW; n = 13); and (3) cycling with normal progestagen and prolactin patterns (CYCLING; n = 8). Both oxytocin and serotonin were elevated in hyperprolactinemic elephants. Thus, we propose that stimulatory factors may play a role in the observed Hyperprolactinemia in this species. Interestingly, rather than being reduced as hypothesized, urinary dopamine was elevated in hyperprolactinemic elephants compared to CYCLING and LOW prolactin groups. Despite its apparent lack of regulatory control over prolactin, this new evidence suggests that dopamine synthesis and secretion are not impaired in these elephants, and perhaps are augmented.
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Hyperprolactinemia is not associated with hyperestrogenism in noncycling african elephants loxodonta africana
General and Comparative Endocrinology, 2013Co-Authors: Natalia A Pradooviedo, Elizabeth J Malloy, Xinyi Deng, Janine L BrownAbstract:African elephants in US zoos are not reproducing at replacement levels. This is in part due to physiological problems, one of which is abnormal ovarian cyclicity that has been linked to increased prolactin secretion (Hyperprolactinemia). A relationship between increased estrogen production (hyperestrogenism) and Hyperprolactinemia has been found in other species. Therefore, the objective of this study was to determine if elevated prolactin was associated with increased estrogen concentrations in non-cycling African elephants. In cycling elephants (n=12), prolactin secretion followed a normal cyclic pattern, with higher concentrations observed during the follicular phase; overall mean concentration was ∼18ng/ml and baseline prolactin was ∼6ng/ml. Non-cycling females (n=18) were categorized into three groups: (1) low prolactin ( 31ng/ml; n=8). Mean urinary estrogen conjugate concentrations ranged from 5.4 to 41.4ng/mg Crt, and were similar between normal cycling (15.4±1.5ng/mg Crt) and non-cycling, low prolactin elephants (18.4±7.3ng/mg Crt), but were lower in moderate (9.4±1.3ng/mg Crt) and marked hyperprolactinemic (9.8±1.1ng/mg Crt) groups (P<0.05). In conclusion, African elephants appear to be sensitive to alterations in prolactin production, with both low (e.g., a non-cycling pattern) and high prolactin secretion being associated with abnormal ovarian activity. However, hyperestrogenism was not related to Hyperprolactinemia in the non-cycling females.
Masami Ono - One of the best experts on this subject based on the ideXlab platform.
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individualized high dose cabergoline therapy for hyperprolactinemic infertility in women with micro and macroprolactinomas
Obstetrical & Gynecological Survey, 2010Co-Authors: Masami Ono, Nobuhiro Miki, Kosaku Amano, Takakazu Kawamata, Toshiro Seki, Rena Makino, Kazue Takano, Shunichiro Izumi, Yoshikazu Okada, Tomokatsu HoriAbstract:The dopamine receptor agonist, bromocriptine, has been first-line treatment for hyperprolactinemic infertility in young women of reproductive age with pituitary hormone-producing adenomas for the past 30 years. Several studies have shown that cabergoline has superior efficacy and tolerability, and in recent years, it has replaced bromocriptine as the first-choice dopamine agonist in this population. In women with hyperprolactinemic amenorrhea, cabergoline corrects Hyperprolactinemia and is more effective than bromocriptine in achieving recovery of the ovulatory cycle. Although cabergoline can induce pregnancy in prolactinoma patients, the rate of pregnancy induction in these women is unknown. In patients with macroprolactinomas (macroadenomas), its effectiveness for controlling tumor growth and thereby inducing successful pregnancy is also unknown. The aim of this study was to determine the efficacy and safety of cabergoline in pregnancy induction and its outcomes in infertile women with prolactinomas. Between 2001 and 2005, the participants—85 infertile women with macroprolactinomas (n = 29) or microprolactinomas (n = 56)—received prospective, high-dose cabergoline therapy for suppression of prolactin and tumor shrinkage. Of the 85 subjects, 31 were bromocriptine resistant, 32 were bromocriptine intolerant, and 22 were newly diagnosed untreated patients. Conception was withheld in patients with microadenomas or macroadenomas until 3 regular menstrual cycles returned and in women with macroadenomas until tumors shrunk to less than 1 cm in height. The drug was withdrawn at the fourth gestational week. Cabergoline corrected and normalized Hyperprolactinemia, increased serum progesterone levels and achieved recovery of the ovulatory cycle in all patients. Within 6 to 24 months after the initiation of cabergoline therapy, all tumors contracted, and 11 of the 29 macroadenomas and 29 of the 56 microadenomas disappeared. Of the 85 patients, 80 (94%) conceived 95 pregnancies; 2 of the 95 were second pregnancies conceived without use of cabergoline. The drug dose at the first pregnancy varied widely (0.25-9 mg/week overall and 2-9 mg/week in bromocriptine-resistant patients). Of the 93 pregnancies induced with cabergoline, 86 resulted in 83 single live births, 1 stillbirth, and 2 abortions (1 of which was spontaneous); the remaining 7 pregnancies were ongoing. All newborns were healthy, without malformations or abnormal development. None of the mothers experienced impaired vision or headache suggestive of abnormal macroprolactinoma re-expansion during pregnancy. These findings show that cabergoline can safely induce and promote successful pregnancy in most infertile women with prolactinoma, independent of tumor size or bromocriptine resistance and intolerance. Cabergoline monotherapy has the potential to substitute for the conventional combination therapy of surgery or radiotherapy plus bromocriptine in patients with macroadenomas.
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individualized high dose cabergoline therapy for hyperprolactinemic infertility in women with micro and macroprolactinomas
The Journal of Clinical Endocrinology and Metabolism, 2010Co-Authors: Masami Ono, Nobuhiro Miki, Kosaku Amano, Takakazu Kawamata, Toshiro Seki, Rena Makino, Kazue Takano, Shunichiro Izumi, Yoshikazu Okada, Tomokatsu HoriAbstract:Context: Cabergoline is effective for hyperprolactinemic hypogonadism. However, the rate of cabergoline-induced pregnancy in women with prolactinoma remains unknown. Also unknown is whether cabergoline can control tumor growth and thereby achieve successful pregnancy in patients with macroprolactinomas. Methods: Eighty-five women with macroprolactinomas (n = 29) or microprolactinomas (n = 56) received prospective, high-dose cabergoline therapy for infertility based on individual prolactin suppression and/or tumor shrinkage. The patients included 31 bromocriptine-resistant, 32 bromocriptine-intolerant, and 22 previously untreated women. Conception was withheld until three regular cycles returned in women with microadenoma and until tumors shrank below 1.0 cm in height in women with macroadenoma. Cabergoline was withdrawn at the fourth gestational week. Results: Cabergoline normalized Hyperprolactinemia and recovered the ovulatory cycle in all patients. All adenomas contracted, and 11 macroadenomas and 29 m...
Jonathan Webster - One of the best experts on this subject based on the ideXlab platform.
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Hyperprolactinemia etiology diagnosis and management
Seminars in Reproductive Medicine, 2002Co-Authors: Peak Mann Mah, Jonathan WebsterAbstract:Hyperprolactinemia is the most common endocrine disorder of the hypothalamic-pituitary axis. A prolactinoma is the most common cause of chronic Hyperprolactinemia once pregnancy, primary hypothyroidism, and drugs that elevate serum prolactin levels have been excluded. Patients can present with hypogonadism, infertility, galactorrhea, osteopenia, and mass effects of the tumor. When Hyperprolactinemia is confirmed, a cause for the disorder needs to be sought. This involves a careful history and examination, followed by laboratory tests and diagnostic imaging of the sella turcica. The goals of treatment are to normalize prolactin levels, restore gonadal function, and reduce the effects of chronic Hyperprolactinemia. Dopamine agonists are the treatment of choice for the majority of patients. Transsphenoidal surgery is usually reserved for patients who are intolerant of or resistant to dopamine agonists or when Hyperprolactinemia is caused by non-prolactin-secreting tumors compressing the pituitary stalk. Cabergoline has been shown to be more effective and better tolerated than bromocriptine. However, there are more data on the safety of the latter drug during pregnancy and bromocriptine, therefore, remains the treatment of choice in hyperprolactinemic women wishing to conceive.
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a comparison of cabergoline and bromocriptine in the treatment of hyperprolactinemic amenorrhea
The New England Journal of Medicine, 1994Co-Authors: Jonathan Webster, Gabriella Piscitelli, A Polli, Carlo Ferrari, Ikram Shah Bin Ismail, M F ScanlonAbstract:Background Cabergoline is a long-acting dopamine-agonist drug that suppresses prolactin secretion and restores gonadal function in women with hyperprolactinemic amenorrhea. We designed a study to compare its safety and efficacy with those of bromocriptine, which has been the standard therapy. Methods A total of 459 women with hyperprolactinemic amenorrhea were treated with either cabergoline (0.5 to 1.0 mg twice weekly) or bromocriptine (2.5 to 5.0 mg twice daily), administered in a double-blind fashion for 8 weeks and subsequently in an open fashion for 16 weeks, during which adjustments in the dose were made according to the response. Of the 459 women, 279 had microprolactinomas, 3 had macroprolactinomas, 1 had a craniopharyngioma, 167 had idiopathic Hyperprolactinemia, and the remainder had an empty sella. Clinical and biochemical status was assessed at 2-week intervals for 8 weeks and monthly thereafter for a total of 6 months, with an additional assessment at 14 weeks. Results Stable normoprolactinem...
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dopamine agonists and pituitary tumor shrinkage
Endocrine Reviews, 1992Co-Authors: John S Bevan, Jonathan Webster, Christopher W Burke, M F ScanlonAbstract:The primary aim of this review has been to clarify the tumor shrinking effects of dopamine agonists on pituitary macroadenomas of different cell types. Shrinkage is most dramatic for macroprolactinomas and is due to cell size reduction. Seventy-nine percent of 271 definite macroprolactinomas were reduced in size by at least 25%, and 89% shrank to some degree. Most shrinkage occurs during the first 3 months of treatment, although in a minority shrinkage is delayed. Dopamine agonist resistance during long-term therapy is exceptional. Drug withdrawal nearly always leads to a return of Hyperprolactinemia, even after several years treatment, although early tumor reexpansion is unusual. About 10% of true macroprolactinomas do not shrink with dopamine agonists; the molecular mechanisms of such resistance have yet to be determined. Alternative formulations of BC and new dopamine agonists (CV 205-502 and cabergoline) are useful for the minority of patients unable to tolerate oral BC, but do not seem to further improve overall shrinkage rates. The risks of pregnancy have probably been overstated, and BC is suitable primary treatment for women with prolactinomas of all sizes; the drug can be used safely during pregnancy in the event of clinically relevant tumor expansion. The interpretation of different degrees of Hyperprolactinemia is discussed and management strategies suggested. Most patients with macroprolactinomas now avoid surgery, but drug-induced, time-dependent tumor fibrosis should be remembered if surgery is contemplated. Nonfunctioning pituitary tumors are mostly of gonadotroph cell origin and may be associated with significant disconnection hyperprolactinaemia. Seventy-six of 84 well-characterized tumors showed no tumor shrinkage during dopamine agonist therapy. Possible explanations include abnormalities of dopamine receptor number and function. Preliminary evidence suggests that dopamine agonists may restrain the growth of some functionless tumors; most of these tumors, however, can be satisfactorily debulked using transsphenoidal surgery. In contrast to macroprolactinomas, other functioning pituitary tumors (GH-, TSH-, and ACTH-secreting) rarely shrink during dopamine agonist therapy, although the number of tumors studied is small.