Prolactin secretion and menstrual function after long-term bromocriptine treatment

Long-term bromocriptine treatment was discontinued in 75 hyperprolactinemic women. Bromocriptine had been given for up to 65 months (median, 24 months). Treatment was reinstituted in 42 women (56%) after 1 to 3 months, mainly because of increasing prolactin levels. Thirty-three women (44%) were followed up for 6 months or more without treatment. Menstrual bleeding occurred in 19 of the 33 women (58%) after 6 months without treatment. The mean prolactin concentration in this group had decreased more than 60% compared with pretherapy concentrations. In 18 of the 42 women who had bromocriptine therapy again, treatment was discontinued a second time. Six of these patients have regular menstrual bleeding. Long-term bromocriptine treatment seems to induce long-standing normalization of prolactin secretion in patients with hyperprolactinemia.     

Effects of long-term treatment with bromocriptine on pituitary prolactinoma in a male

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.     

Pergolide and bromocriptine for the treatment of patients with hyperprolactinemia

A prospective study of 22 women with hyperprolactinemia from various causes was performed with use of bromocriptine in nine patients and pergolide in 13 patients. The administration of 50 micrograms of pergolide followed by 100 micrograms on the second day showed significant decrements (p less than 0.01) in systolic and diastolic blood pressure in either standing or lying position. However, 25 micrograms of pergolide followed by 50 micrograms did not lower blood pressure. Both 25 and 50 micrograms of pergolide induced a maximal and significant (p less than 0.005) inhibition of prolactin at 8 hours and remained suppressed for at least 24 hours. Long-term treatment with either bromocriptine or pergolide was continued for 48 weeks. Both dopamine agonists demonstrated a similar degree of prolactin inhibition throughout time. However, only patients treated with pergolide had higher levels (p less than 0.05) of luteinizing hormone and follicle-stimulating hormone. Resumption of spontaneous menses and cessation of galactorrhea occurred at similar times in both groups. It can be concluded that either dopamine agonist can be safely given to patients with hyperprolactinemia.     

Intermittent bromocriptine treatment for the induction of ovulation in hyperprolactinemic patients

Postovulatory treatment with bromocriptine bears a potential teratogenic risk. Therefore, after restoration of the menstrual cycle in 20 infertile hyperprolactinemic anovulatory patients, treatment was restricted to the follicular phase and the periovulatory period. The resulting intermittent treatment regimen using a dose of 5 mg of bromocriptine/day yielded ovulatory cycles in all 20 patients. Fifteen pregnancies were achieved in thirteen patients, two women becoming pregnant twice. Discontinuation of treatment after ovulation caused hyperprolactinemia during the luteal phase. This did not seem to interfere with the establishment and maintenance of pregnancy. Hyperprolactinemia during the follicular phase may be related to luteal insufficiency.     

Pregnancy after treatment in patients with prolactinoma: operation versus bromocriptine

Prolactinoma was diagnosed in 190 women of the same age range, among whom 88 were treated with transsphenoidal microadenectomy and 102 with bromocriptine. The purpose of this study was to compare the two groups according to classification of the adenomas by size and invasiveness, pregnancy rates, prolactin levels after pregnancy, sella turcica changes after pregnancy, and serum prolactin levels and radiologic changes in patients who were operated on but did not become pregnant or did not desire pregnancy. In the group with operation, 91% of patients who had microadenoma and 88% of those with diffuse adenoma conceived, but none who had invasive tumors did so. In the bromocriptine-treated group, among patients with no visible microadenoma or with microadenoma seen radiologically 56% conceived; among those with diffuse adenoma 66% conceived; no patients with invasive adenoma were in this group. In the group with operation, 21% had higher serum prolactin levels and amenorrhea after pregnancy, compared with 19% in the medical treatment group and 19% in the group with operation who did not conceive. Of all patients studied, radiologic changes in the pituitary fossa were seen in only one patient undergoing operation.     

In vitro fertilization: A long-term follow-up after treatment failure

There is a considerable body of psychological research on women presenting for in vitro fertilization (IVF), but relatively little on the long-term adjustment of such women after unsuccessful treatment. This study examined the adjustment (4–9 years after treatment) of a sample (n = 76) of women whose treatment had failed. At follow-up, it was found that eight (10.53%) of the women had conceived naturally and 16 (21.05%) had become adoptive parents. In comparison with population norms, the women who had not subsequently conceived or adopted (n = 52) were found to rate themselves as more highly stressed (P < 0.001), but rated themselves as higher in self-esteem (P < 0.001). However, when women who remained childless after unsuccessful IVF were compared with those who subsequently conceived or adopted, the former group rated themselves as more stressed (P < 0.05), more depressed (P < 0.001) and with a lower satisfaction with life (P < 0.005) and lower self-esteem (P < 0.05). Women who wished to adopt but were unable to do so made a major contribution to this negative pattern. The study indicates that infertility long after failed IVF treatment contributes to psychological dysfunction. It highlights the need to prepare women better for treatment failure and to ensure appropriate counselling is available when further IVF treatment is no longer appropriate.     

In vitro fertilization: a long-term follow-up after treatment failure

There is a considerable body of psychological research on women presenting for in vitro fertilization (IVF), but relatively little on the long-term adjustment of such women after unsuccessful treatment. This study examined the adjustment (4--9 years after treatment) of a sample (n = 76) of women whose treatment had failed. At follow-up, it was found that eight (10.53%) of the women had conceived naturally and 16 (21.05%) had become adoptive parents. In comparison with population norms, the women who had not subsequently conceived or adopted (n = 52) were found to rate themselves as more highly stressed (P < 0.001), but rated themselves as higher in self-esteem (P < 0.001). However, when women who remained childless after unsuccessful IVF were compared with those who subsequently conceived or adopted, the former group rated themselves as more stressed (P < 0.05), more depressed (P < 0.001) and with a lower satisfaction with life (P < 0.005) and lower self-esteem (P < 0.05). Women who wished to adopt but were unable to do so made a major contribution to this negative pattern. The study indicates that infertility long after failed IVF treatment contributes to psychological dysfunction. It highlights the need to prepare women better for treatment failure and to ensure appropriate counselling is available when further IVF treatment is no longer appropriate.     

A long-acting repeatable form of bromocriptine as long-term treatment of prolactin-secreting macroadenomas: a multicenter study.

OBJECTIVE: To assess the efficacy and tolerability of monthly injections of the long-acting repeatable bromocriptine in patients with macroprolactinomas. DESIGN: Open and prospective trial. SETTING: This multicenter trial was carried out in seven university hospitals. PATIENTS: Forty-two patients with prolactin (PRL)-secreting macroadenomas. INTERVENTIONS: Fifty to 200 mg of the drug were administered intragluteally every 28 days for 6 to 24 months. MAIN OUTCOME MEASURES: The efficacy was assessed by repetitive plasma PRL measurements, visual field determinations, and computed tomography scan examinations. RESULTS: After the first 50-mg injection, the mean percentage decrease of PRL levels was 71% from baseline on day 14; between days 1 and 28, PRL levels were suppressed to normal in nine cases, and a clear tumor shrinkage was documented in 21% of the patients. Normalization of PRL secretion was obtained in 62%, and a clear-cut reduction in tumor size in 50% of the patients after 6 months of treatment. CONCLUSIONS: The long-acting repeatable form of bromocriptine was a well tolerated and quickly effective treatment in most of these patients with macroprolactinomas.     

Polycystic ovary--classification and treatment by bromocriptine

Plasma levels of androstenedione (A) and dehydroepiandrosterone sulfate (DHAS) were measured in 29 women with PCO in an attempt to classify PCO. A and/or DHAS were elevated in all cases. In cases with DHAS levels below 2,000 ng/ml, the A levels were found to be over 1.4 ng/ml. This group was defined as an ovarian type because the major source of A is the ovary. In contrast, women whose DHAS levels were higher than 2,000 ng/ml were classified as an adrenal type. In both groups, the hormonal features were elevated LH levels and exaggerated LH response to LHRH. The mean A levels were 2.43 +/- 0.31 ng/ml in ovarian type and 2.20 +/- 0.42 ng/ml in adrenal type. The mean DHAS levels for the adrenal type were 3,052 +/- 299 ng/ml, or about 3 times as high as normal values. On the other hand, those for the ovarian type were on the upper borderline of the normal range. In both groups, dexamethasone lowered DHAS levels by about 80% with no discernible effect upon A levels. The successful rate for ovulation-induction by clomiphene was 20% in the ovarian and 33% in the adrenal. Bromocriptine induced ovulation in 8 out of 9 cases of the ovarian type. However, only one of 6 responded to bromocriptine in the adrenal type. Bromocriptine-unresponsive cases of the adrenal type ovulated following treatment with combination of clomiphene and prednisolone. In summary, we attempted to classify PCO into ovarian and adrenal types by analyzing the elevated androgen level. This classification seems to be useful in the treatment of PCO and also provides some insight into the pathogenesis of PCO.     

Comparison of placebo and bromocriptine in the treatment of patients with normoprolactinaemic amenorrhoea.

Fourteen women with normoprolactinaemic amenorrhoea were treated with bromocriptine (2.5 mg twice daily) for a period ranging from 4 to 17 weeks, while a matched group fo 19 amenorrhoeic women were treated with a placebo (one tablet twice daily) for 4 to 12 weeks. About half of the patients in both groups had at least one episode of vaginal bleeding during treatment. There was no clear difference in the menstrual and ovulatory pattern between placebo and bromocriptine groups.     

Normalization of visual fields following bromocriptine treatment in hyperprolactinemic patients with visual field constriction

Two patients with galactorrhea-amenorrhea and bilateral visual field defects were studied. Routine radiologic examination of each patient revealed a normal sella turcica and no demineralization of the posterior clinoid process. Serum prolactin levels were elevated (patient V. G., 80 ng/ml; patient S. R., 204 ng/ml). Within 2 months of bromocriptine therapy, the serum prolactin levels were normal (patient V. G., 12.21 ng/ml; patient S. R., 8.25 ng/ml) and the bilateral visual field defects were corrected. Bromocriptine has been shown to control prolactin secretion in patients with prolactin-secreting pituitary tumors. Normalization of restricted visual fields following bromocriptine therapy indicates the possibility of an anatomical regression of pituitary hyperplasia or an underlying prolactin-producing microadenoma. It is speculated that the modality of functional galactorrhea reflects hyperplasia of the lactotrophs preceding a nodular and ultimately an adenomatous change. The continuous and prolonged administration of bromocriptine may prevent such a progressive sequence. Further experience is required to validate this possibility.     

Gynecological laparoscopy and treatment of ectopic pregnancy

The aim of the present study is to show the advantages of the gynecologic laparoscopy for the diagnosis and treatment of the intact tubal pregnancy. For the fulfillment of this aim was made a prospective study for 5 years' period of the patients with diagnosis "Ectopic pregnancy", treated in Gynecological clinic of UMBAL-Pleven. The objects of observation were 33 women with diagnosis: "Intact ectopic pregnancy". Methotrexate was used by plan for 6 patients, in 7 patients was made laparotomy, and in 20 patients--gynecological laparoscopy. From the performed 20 gynecological laparoscopy, 16 women were recovered laparoscopically, in 14 of which was made partial salpingectomy, and in 2--milking. In one of the last two patients was injected Methotrexate in the bed of the gestational bag. In 4 women was necessary laparotomy, because of impossibility of performing of laparoscopic surgery. The authors emphasized the advantages of the gynecological laparoscopy for precise diagnosis and contemporary treatment of the intact ectopic pregnancy.     

Hyperprolactinemia and hypophyseal tumors--results of treatment with bromocriptine

Forty-one patients with hyperprolactinemia are presented. They were divided into two groups. In the first group, 11 or 27% women had radiological evidence of a pituitary tumour. Seven of 11 patients conceived by means of the bromocryptine treatment. The visual impairment in one patient in the tenth week of pregnancy disappeared after the re-institution of bromocryptine. The values of prolactin in this group varied between 4000 and 7000 mIE/ml. In the second group, 30 or 73% women were without radiological evidence of a pituitary tumour. The values of prolactin in this group ranged from 1200 to 5000 mIE/ml. Fourteen of 30 patients conceived by means of the bromocryptine treatment.     

Intranasal buserelin versus surgery in the treatment of uterine leiomyomata: long-term follow-up

Forty-two women with symptomatic uterine myomas, candidates for myomectomy or hysterectomy, were randomized to 6 months' treatment with buserelin 1200 micrograms/day intranasally (n = 22) or immediate surgery (n = 20). After buserelin treatment or operation the patients were followed for at least 12 months. Buserelin was well tolerated, the uterine volume fell from 465 +/- 168 to 273 +/- 88 cm3, and hemoglobin values normalized in all anemic patients. Rapid myoma regrowth was observed in all patients in the buserelin group after treatment withdrawal. Pregnancy occurred during follow-up in one of five buserelin-treated myomectomy candidates. Menorrhagia recurred in eight of 15 buserelin-treated hysterectomy candidates, and a hysterectomy was required but no transfusion was needed. Two women entered natural menopause and were considered cured. In the surgery group all operations were uneventful: three women conceived after myomectomy, whereas four of the patients that underwent hysterectomy required transfusions. Thus buserelin treatment appears to be indicated for infertile patients when surgery is contra-indicated or could cause adhesions, and for hysterectomy candidates in perimenopausal age and/or with secondary anemia.     

Pregnancy after combined treatment with bromocriptine and tamoxifen in two patients with pituitary prolactinomas

Two patients with prolactinomas who could not tolerate a large dose of bromocriptine were treated with combination of bromocriptine and tamoxifen. This combined therapy normalized the PRL level and restored a regular ovulatory cycle, which resulted in pregnancy.     

Atypical endometrial hyperplasia treatment with progestogens and gonadotropin-releasing hormone analogues: long-term follow-up

OBJECTIVE: The aim of this study was to assess the long-term effect of gonadotropin-releasing hormone analogues (GnRH-a) in combination with high-dose progestogens in the treatment of atypical endometrial hyperplasia in selected surgical high-risk patients and in women desiring reproductive potential. We hypothesized that this therapy is effective for most couples. METHODS: In the Department of Gynecology of a university hospital, a conservative treatment was offered to a series of 22 patients with atypical endometrial hyperplasia who had a surgical or anesthetic risk history or wished to preserve their fertility potential. After informed consent, they were treated with 500 mg norethisterone acetate weekly for 3 months and 3.75 mg Triptorelin depot every month for 6 months. Three patients failed to complete the study, so the group finally consisted of 19 subjects. They were prospectively followed for 5 years by hysteroscopy and multiple selected biopsies every 6 months. RESULTS: At a 5-year follow-up, regression was noted in 16 patients (84.2%), persistence in 1 (5.1%), recurrence in 1 (5.1%), and progression in 1 (5.1%). CONCLUSION: Consistent with our hypothesis, combined treatment with progestogens and GnRH-a is an effective alternative in selected patients with atypical endometrial hyperplasia.     

Use of bromocriptine in the treatment of normoprolactinemic infertility

The efficacy of bromocriptine therapy was studied in 84 normoprolactinemic infertile patients. Bromocriptine (2.5-5.0 mg/day) was given for at least 1 month. Bromocriptine therapy was effective in 54 of 84 cases (64%), including 6 of 15 (40%) cases with amenorrhea, 16 of 24 cases (67%) with anovulatory cycle, 9 of 15 cases (60%) with delayed ovulation and 23 of 30 cases (77%) with luteal phase defect. Sixteen cases were able to conceive with bromocriptine alone. Twenty-five patients who did not respond to bromocriptine were treated with a combination therapy consisting of bromocriptine and clomiphene. Of the 25 cases, 14 responded to the therapy, and 6 of them were able to conceive. The response of prolactin to domperidone (10 mg, i.v.) was significantly (p less than 0.01) higher in the group responding to bromocriptine than in the nonresponding group. These results indicate that the administration of bromocriptine is an effective therapy for patients with normoprolactinemic endocrine disorders, and that domperidone may be useful in selecting the candidates for bromocriptine therapy.