David F. Archer

Endometrial morphology in asymptomatic postmenopausal women

Few data are available regarding endometrial histologic features in asymptomatic perimenopausal and postmenopausal women. This study encompasses endometrial biopsy specimens obtained from 801 such women before enrollment in a multicenter study of estrogen-progestin replacement. One endometrial cancer was found (0.13%); four additional biopsy specimens showed atypia (total 0.63%). The endometrium was atrophic in 373 (46.9%), proliferative in 133 (16.7%), secretory in 54 (6.8%), and hyperplastic in 41 (5.2%). Insufficient tissue for diagnosis was obtained in 195 (24.5%). We conclude that the yield for neoplasia is so low that screening endometrial biopsy is not justified in asymptomatic perimenopausal and postmenopausal women.

Endometriosis-associated pelvic pain: evidence for an association between the stage of disease and a history of chronic pelvic pain

OBJECTIVE To track the severity and location of pelvic pain associated with endometriosis throughout the reproductive-age years and to evaluate the association between these pain parameters and the stage of disease. DESIGN Historical prospective study. SETTING Tertiary care center. PATIENT(S) Forty-eight women with endoscopically staged endometriosis and chronic pelvic pain who had undergone medical and/or conservative surgical therapy. INTERVENTION(S) Each participant was administered a questionnaire that included a determination of the severity and location of her pain. MAIN OUTCOME MEASURE(S) The stage of disease, the area of the pelvis that contained the bulk of disease, the severity of pain, and the location of the most severe pain were recorded. RESULT(S) The mean duration from the initial diagnosis until follow-up was 15.7 +/- 3.1 years, Twenty-one (43.8%) subjects denied any symptoms of pain on follow-up evaluation. Of the 27 patients with persistent pain, 21 (78%) identified the location of their most severe pain as being the same as at initial diagnosis. The stage of disease at initial diagnosis was significantly associated with a higher degree of pain at follow-up. CONCLUSION(S) These data suggest that endometriosis-associated chronic pelvic pain commonly persists throughout the reproductive years and that endometriosis stage is directly related to the persistence of pelvic pain.

The effects of bolus administration of opioids on cerebrospinal fluid pressure in patients with supratentorial lesions

In many studies reporting an increase in cerebrospinal fluid pressure (CSFP) after opioid administration, concomitant decreases in mean arterial pressure (MAP) have been observed.Autoregulatory cerebral vasodilation may therefore have been a factor in the CSFP increases. We tested the hypothesis that increases in CSFP after bolus injection of opioids could be minimized by modifying concomitant decreases in MAP with phenylephrine. Thirty-three patients with supratentorial mass lesions were studied in a randomized, prospective, double-blind, saline-controlled comparative trial. The principal outcome measures were lumbar CSFP, MAP, and heart rate (HR). Study drugs, sufentanil 0.8 micro gram/kg (n = 12), fentanyl 4.5 micro gram/kg (n = 11), or normal saline (n = 10), were injected intravenously (IV) during stable general anesthesia with 0.3-0.7 minimum alveolar anesthetic concentration (MAC) of isoflurane in oxygen and controlled ventilation (end-tidal carbon dioxide 32-35 mm Hg). Phenylephrine 50-100 micro gram was injected IV when MAP decreased by more than 15% of initial values, and atropine 0.5 mg IV when HR decreased to less than 45 bpm. Opioid administration was associated with significant decreases in MAP, 21 +/- 9 mm Hg (mean +/- SD) in the sufentanil group and 16 +/- 7 mm Hg in the fentanyl group; P < 0.001. These decreases in MAP were of short duration (i.e., corrected with 1-2 min). Patients in the sufentanil group needed more phenylephrine than patients in the fentanyl group (170 +/- 89 micro gram vs 100 +/- 47 micro gram; P < 0.05). No significant change in the CSFP was seen in either the sufentanil-(1 +/- 6 mm Hg) or fentanyl-treated patients (0 +/- 2 mm Hg). No significant changes in MAP or CSFP were observed in the saline-treated patients. HR decreased after injection of either study drug (P < 0.01) but remained unchanged in the saline group. In summary, during stable anesthesia with isoflurane in oxygen, bolus injections of fentanyl or sufentanil, despite producing rapidly corrected mean decreases in MAP of 18% and 25%, respectively, were not associated with any change in CSFP. (Anesth Analg 1996;82:600-6)

Management of pelvic endometriosis with low-dose danazol*†

Thirty-eight women with pelvic endometriosis diagnosed by laparotomy or laparoscopy were enrolled in a double-blind study utilizing danazol. Danazol was administered for 6 months in four doses schedules: 600, 400, 200, and 100 mg/day. At the completion of 6 months of therapy, repeat laparoscopy was performed and 71% of the women were found to have improvement of pelvic endometriosis. Minimal and moderate pelvic endometriosis appeared to respond well to doses of danazol of less than 400 mg/day, whereas severe endometriosis appeared to be best treated with danazol doses of greater than 400 mg/day. Symptomatic relief of pain, dysmenorrhea, and dyspareunia occurred in 89% of the women. The over-all pregnancy rate in women attempting conception was 28% (8 of 28). Fifty-four per cent of the women had recurrence of symptoms within 1 year of discontinuation of danazol.

Amenorrhea and galactorrhea: Results of therapy with 2-Brom-α-ergocryptine (CB-154)☆

Abstract Administration of Brom-ergocryptine (CB-154 ∗ ) has a dramatic effect on breast secretion. Inhibition of lactation occurs within three to four weeks in women with amenorrhea and galactorrhea. Resumption of normal ovulatory function was documented by serum progesterone levels, as well as pregnancy, in three of four women attempting to conceive. Serum prolactin levels become normal following initiation of Brom-ergocryptine. Discontinuation of Brom-ergocryptine was found to result in a return of both inappropriate lactation and elevation of serum prolactin in this study. No deleterious side effects of Brom-ergocryptine have been found in any of the volunteers either clinically or on the basis of sequential laboratory studies.

Current Concepts of Prolactin Physiology in Normal and Abnormal Conditions

Currently the physiology and pathophysiology of pituitary prolactin secretion are under intensive investigation. Development of sensitive, specific radioimmunoassays for hPRL and improved roentgenographic techniques have increased the diagnostic acumen for incipient pituitary microadenomas. Several modalities of treatment are available at the present time which can result in improvement in the clinical symptoms of the amenorrheagalactorrhea syndromes. Eponymic classification of amenorrhea-galactorrhea syndromes should be discarded and appropriate diagnostic studies initiated to determine the etiology of the inappropriate breast secretion and/or elevated serum hPRL level.

Response of Serum Prolactin to Exogenous Stimulation

Previous observations by other workers indicating suppression of serum prolactin (hPRL) by water loading could not be confirmed. Sequential testing using an acute water load in patients with various clinical diagnoses did not aid conclusively in differentiating functional hyperlactinemic states from pituitary adenoma. It was of interest that the acute ingestion of water resulted in a triphasic response in serum hPRL levels. The response to breast stimulation was more marked in patients with excessive breast hypertrophy and galactorrhea. This was in contrast to patients with hypo- or hyperthyroidism, anorexia nervosa, and our normal subjects. In response to breast stimulation, there was no difference among the normal group, women with functional hyperlactinemia, and patients with proven pituitary adenoma. When they were compared with other patient groups in this study, marked responsiveness was found in patients with amenorrhea and galactorrhea, amenorrhea with elevated hPRL levels without galactorrhea, breast hypertrophy, and adrenal overactivity in response to these two stimuli. The physiologic mechanisms resulting in the increase in serum hPRL levels seen in these patients remain unclear at the present time.

The effect of skull-pin insertion on cerebrospinal fluid pressure and cerebral perfusion pressure : Influence of sufentanil and fentanyl

This randomized prospective study measured the effects of an intravenous opioid bolus on cerebrospinal fluid pressure (CSFP), mean arterial pressure (MAP), and cerebral perfusion pressure (CPP) during skull-pin insertion. Twenty-two adult patients scheduled for elective craniotomy for supratentorial lesions were studied. Outcome variables were MAP, heart rate (HR), and lumbar CSFP. The standardized anesthetic egimen included fentanyl (2 micro g/kg), thiopental (5-7 mg/kg), lidocaine (1.5 mg/kg), isoflurane (0.3-0.7 minimum alveolar anesthetic concentration), and vecuronium (0.1 mg/kg). During stable anesthesia, sufentanil (0.8 micro g/kg) or fentanyl (4.5 micro g/kg) was given as a bolus before skull-pin insertion. The hemodynamic effects of the opioid injection were modified with phenylephrine and/or atropine when indicated. CSFP remained unchanged in both treatment groups. MAP and CPP increased approximately 10 mm Hg after skull-pin insertion (P<0.001). In the sufentanil group, HR decreased approximately 10 bpm after opioid injection and remained decreased throughout the study. In fentanyl-treated patients, HR decreased 8 bpm after opioid injection but returned to preopioid rates after skull-pin insertion. In conclusion, in anesthetized patients, an intravenous bolus of fentanyl or sufentanil prior to skull-pin insertion results in stable values of CSFP, CPP, BP, and HR when the hemodynamic effects of the opioid are modified with phenylephrine and atropine. (Anesth Analg 1997;84:1292-6)

Bromocriptine treatment of women with suspected pituitary prolactin-secreting microadenomas

The present study was designed to investigate the efficacy of bromocriptine in reducing serum prolactin (PRL) levels and in decreasing the size of PRL-secreting microadenomas. Bromocriptine, 5.0 mg, was administered daily for 2 years of 17 women who had galactorrhea, hyperprolactinemia, and hypocycloidal polytomographic evidence suggestive of a pituitary microadenoma. Serum PRL levels were normalized in 16 of 17 women during therapy. Associated with this was resumption of regular menses in 15 of 16 women with menstrual dysfunction and cessation of galactorrhea in 16 of the 17 women. Improvement in the roentgenographic appearance of the sella turcica occurred in two women. No progression in tumor size was found during the course of therapy. Side effects attributed to bromocriptine were minimal, transient, and usually well tolerated. These data suggest that bromocriptine is an appropriate therapeutic modality for PRL-secreting pituitary microadenomas.

Pituitary Gonadotropin Response in Women with Idiopathic Hyperprolactinemia

Inappropriate lactation and idiopathic hyperprolactinemia are frequently associated with amenorrhea. In these individuals, peripheral levels of follicle-stimulating hormone (hFSH) are usually normal, and luteinizing hormone (hLH) levels are often found in the low-normal range. The present study was undertaken to evaluate the functional capacity of the pituitary by the response of hFSH and hLH to synthetic gonadotropin-releasing hormone (Gn-RH). Six women with amenorrhea, inappropriate breast secretion, and idiopathic hyperprolactinemia (prolactin levels ranged from 45 to 355 ng/ml) were given 100 mug of Gn-RH intramuscularly. Serum hFSH and hLH levels were assessed in samples obtained at 15-minute intervals over the next 2-hour period. Initial hFSH levels were normal in all women, with a mean of 242 +/- 72 ng/ml. The absolute increase after Gn-RH administration averaged 486 +/- 193 ng/ml. Serum hLH was below normal in three of the six women, and normal in the remaining three women initially. The absolute increase averaged 1308 +/- 315 ng/ml. The greatest percentage increase in hLH was found in the women with the subnormal basal titers. In these women, hLH rose from a mean of 22 ng/ml to a mean of 1092 ng/ml. These data demonstate an exaggerated increase in hFSH and hLH levels after exogenous Gn-RH administration. This suggests that the amenorrhea associated with elevated serum prolactin levels is principally of hypothalamic origin.