Val Davajan

Longitudinal evaluation of patients with untreated prolactin-secreting pituitary adenomas

A group of 43 patients with galactorrhea, hyperprolactinemia, and radiographic evidence of pituitary adenomas were followed from 3 to 20 years. Initial polytomography and computerized tomographic (CT) scans revealed no evidence of extrasellar extension. Serum levels of prolactin (PRL) were measured at 6 month intervals, and visual fields were assessed annually. Polytomograms and CT scans were repeated every 9 to 36 months. During the period of follow-up, CT scans (but not polytomograms) indicated tumor enlargement in two patients, both of whom underwent selective transsphenoidal removal of the tumor. Polytomograms and CT scans did not show any change in the other 41 patients, and three of them have resumed normal menses, are no longer lactating, and have normal PRL levels. The initial results of this ongoing study indicate that most patients with small pituitary adenomas can be followed with annual CT scans with or without medical therapy, and that surgical treatment should be reserved for those patients with large tumors, those with visual-field loss, and those who show signs of enlargement of the tumor.

Monitoring techniques to predict and detect ovulation

This study was designed to evaluate the accuracy of various methods in predicting and detecting ovulation in 14 spontaneous and 17 clomiphene citrate (CC)-induced cycles. From cycle day 11 all subjects (n = 27) were followed with daily transvaginal ultrasound; rapid measurement of serum luteinizing hormone (LH) and estradiol (E2); determination of urinary LH with First Response (Tambrands Inc., Palmer, MA) and Ovustick (Monoclonal Antibodies, Inc., Mountain View, CA) kits; and recording of basal body temperature (BBT). The results demonstrated that transvaginal ultrasound detected ovulation in all cycles. Mean daily serum LH levels were similar in both groups, and peak values of 40 mIU/ml or greater preceded the day of ovulation in all cycles. Serum E2 peak was significantly greater in CC cycles (961 +/- 96 versus 463 +/- 39 pg/ml) (P less than 0.01) and preceded the LH peak in 97% of the cycles. First Response and Ovustick predicted ovulation in 53.3% and 87.5% of the cycles, respectively (P less than 0.01). BBT nadir predicted the day of ovulation in only 10% of cycles. In conclusion, this study revealed that transvaginal ultrasound is an excellent method for detection of ovulation and that Ovustick is a very useful method for prediction of the day of ovulation.

An in vivo system in man for quantitation of estrogenicity

A modified method of measuring the binding capacity of corticosteroid-binding globulin (CBG-BC) in serum using 3H-cortisol saturation-charcoal adsorption is described. Forty serum samples per day can be assayed in duplicate, each sample with a heated nonspecific binding blank (60 degrees C.). The interassay coefficient of variation is less than 6 per cent. All age groups of men and women had similar levels of CBG-BC, except postmenopausal women, whose levels were higher (15.9 +/- 0.2 vs. 18.7 +/- 0.8 microgram per 100 ml., mean +/- standard error of the mean, respectively; z = -3.51, p less than 0.001). The variance of serum levels of CBG-BC throughout the menstrual cycle in five women was small (coefficient of variation = 13 per cent) and showed no relationship to the marked and cyclic changes in estradiol levels (coefficient of variation = 73 per cent). In pregnancy the levels of CBG-BC increased linearly after estradiol levels exceeded 1,300 pg. per milliliter and after estrone levels exceeded 500 pg. per milliliter (r = 0.88, p less than 0.001; and r = 0.85, p less than 0.001, logarithmic regression analysis). The findings of this study indicate that serum levels of CBG-BC are relatively constant in men and menstruating women. In pregnancy after a high threshold of endogenous estrogen is reached, CBG-BC increases in a direct dose-response manner as levels of estradiol increase further.

An extended regimen of clomiphene citrate in women unresponsive to standard therapy

An extended regimen of clomiphene consisting of 250 mg of clomiphene for 8 days followed by the administration of 10,000 IU of human chorionic gonadotropin (hCG) 6 days later was administered to 13 oligomenorrheic women who had previously failed to ovulate when treated with 250 mg of clomiphene for 5 days and hCG. Eight of these 13 women ovulated. Their postovulatory mean progesterone (P) level 7 days after hCG was 16 +/- 2 ng/ml. Three pregnancies occurred during 25 treatment cycles. Posttreatment estrogen levels were higher when women were treated for 8 days than for 5 days. Women ovulating after 8 days of treatment had increased concentrations of luteinizing hormone (LH) and testosterone (T) prior to hCG administration and higher pretreatment levels of estrogen and T, compared with women who did not ovulate. Changes in the timing of hCG administration may induce ovulation in some women who fail to ovulate when hCG is given on day 14. Because this 8-day regimen of clomiphene and hCG was successful in more than 50% of women failing to ovulate after 5 days, this regimen should be used prior to human menopausal gonadotropin (hMG) therapy.

An in vivo system in man for quantitation of estrogenicity. II. Pharmacologic changes in binding capacity of serum corticosteroid-binding globulin induced by conjugated estrogens, mestranol, and ethinyl estradiol.

Abstract The effects of various dosages of orally administered conjugated estrogens, mestranol, and ethinyl estradiol upon the binding capacity of serum corticosteroid-binding globulin (CBG-BC) were studied. When different dosages of conjugated estrogens were given to postmenopausal women, these was a dose-response increase in CBG-BC (r = 0.88, p

The significance of glactorrhea in patients with normal menses, oligomenorrhea, and secondary amenorrhea

Thyroid-stimulating hormone and prolactin (PRL) were measured in a group of 149 women with galactorrhea. Three of these patients were found to have primary hypothyroidism. In the remaining 146 patients, the PRL assay was correlated with the menstrual history and the results of hypocycloidal polytomography. Sixty-two per cent of these patients had hyperprolactinemia and 35 per cent had abnormal tomograms. Nine patients with abnormal x-rays had normal prolactin levels. None of the patients with normal menses and normal PRL was found to have an abnormal x-ray. Fourteen of the 15 patients with PRL levels greater than 200 ng. per milliliter had abnormal tomograms. Almost 70 per cent of patients with secondary amenorrhea and low estrogen status had abnormal x-rays. In patients with oligomenorrhea and secondary amenorrhea with normal estrogen status, it was not possible to differentiate between patients with normal or abnormal tomograms based on the level of serum PRL. Polytomography remains the single most important diagnostic test in establishing the presence of a pituitary tumor.

The cervical factor in infertility: diagnosis and treatment.

One hundred and fourteen women with an abnormal fractional postcoital test (PCT) and no other demonstrable cause of female infertility were included in this study. By utilizing the results of the postcoital test, it was possible to divide the patients into three major groups: (1) those with anatomical cervical defect, (2) those with abnormal cervical mucus, and (3) those with an abnormal PCT and normal cervical mucus. In the latter group the abnormality was due to either an abnormal male factor or an undetermined factor. The treatment used in all cases was either steroidal (diethylstibestrol) or mechanical (cervical cup insemination). In 53 of the patients there was an improvement in the PCT as a direct result of therapy. Twenty-three of these patients became pregnant--a pregnancy rate of 43%. Of the entire group of 110 patients (excluding 4 patients whose husbands had azoospermia), only 21% became pregnant. Of the 57 patients who failed to respond to therapy, 41 have been followed for 1 year, and only 2 pregnancies have been noted without therapy. No correlation was found between an abnormal PCT and the immunologic factor.

Clinical response to CB-154 and the pituitary response to thyrotropin-releasing hormone-gonadotropin-releasing hormone in patients with galactorrhea-amenorrhea.

Ten patients with galactorrhea and amenorrhea were treated with 2-bromo-alpha-ergocryptine (CB-154). All patients had normal anteroposterior and lateral x-rays of the sella turcica and normal or low gonadotropin levels. Before treatment, serum prolactin (PRL) levels were between 80 and 1575 ng/ml. Prior to initiating therapy, six patients were further evaluated by the intravenous administration of thyrotropin-releasing of a pituitary etiology in all patients. During treatment, PRL levels were measured at monthly intervals. After 1 month, serum PRL concentrations were reduced between 13% and 99%. In eight subjects there was complete cessation of galactorrhea. During treatment, nine patients resumed ovulatory menstrual cycles and three patients conceived. After discontinuing therapy, five of seven subjects had a recurrence of galactorrhea, amenorrhea, and hyperprolactinemia.

A simplified technique for evaluation of the biophysical properties of cervical mucus

A simplified technique for evaluating the biophysical properties of cervical mucus was presented. The mucus was stretched on a microscope slide, and a cover slip was placed over a portion of the sample and dried for 24-48 hours at 37 degrees C. Photomicrographs were taken under dark-field illumination. Mucus samples representative of the normal midcycle (Day 12), proliferative phase (Day 8), secretory phase (Day 26), and midcycle from an infertile patient with diagnosis of hostile cervical mucus were examined. The normal midcycle mucus showed linear alignment of dendritic crystals. The proliferative sample showed linear alignment, but the dendritic crystals were sparse, widely spaced, and reduced in branching compared with the normal midcycle mucus. Secretory mucus showed the dendritic crystals in a network pattern instead of in the linear alignment. The abnormal (infertile) midcycle mucus showed evidence of alignment; however, the dendritic crystals were very wide and appeared obstructive. These results indicate that there is a cyclic change in cervical mucus which is reflected in the pattern of the dendritic crystals formed.

Galactorrhea and pituitary tumors in postpill and non-postpill secondary amenorrhea

One hundred sixty-seven women with secondary amenorrhea were observed from six months to four years. In 66 patients, the amenorrhea followed the discontinuation of oral contraceptives (postpill) while in the remaining 101 the amenorrhea was not temporally pill related (non-postpill). Galactorrhea was present in 43 (65%) of those with postpill amenorrhea and in 32 (32%) of those with non-postpill amenorrhea (p less than 0.001). Tomography of the sella turcica was performed in the 75 women with galactorrhea and in the 35 without galactorrhea who did not have withdrawal uterine bleeding following progesterone administration and who had low or normal serum follicle-stimulating hormone levels (hypothalamic-pituitary failure). Forty of the 75 patients with amenorrhea and galactorrhea had radiographic evidence of a pituitary tumor whereas only eight of 35 patients with hypothalamic-pituitary failure without galactorrhea had an abnormal sella turcica (p less than 0.01). The incidence of radiographic abnormalities in those with galactorrhea was similar in both the postpill and non-postpill groups.