John B. Josimovich

Prostaglandin Content of Human Endometrium

Prostaglandin levels in 46 human endometrium specimens were determined and expressed as both total uterine content and on a dry weight basis. Concentrations of PGF2alpha and PGE did not differ significantly between specimens obtained during the proliferative or secretory phases of the menstrual cycle. There was, however, a fourfold higher total uterine content of prostaglandins during the secretory phase. There was also a more than fourfold higher level of PGF2alpha than of PGE during the secretory phase. The two types of prostaglandins were present in nearly equal amounts during the proliferative phase. Atrophic endometrium was characterized by a high concentration of prostaglandins, but a low total amount consisting of nearly equal amounts of PGF2alpha and PGE.

Serum prolactin in patients with inappropriate lactation

Abstract Serum prolactin (HPRL) was evaluated with a specific double-antibody radioimmunoassay in 50 women with inappropriate lactation. The results allowed classification of patients on the basis of the basal prolactin values. Nineteen of the patients (38 per cent) had elevated serum HPRL values, and all 19 had amenorrhea. In this group there was increased incidence of endocrine dysfunction. In 31 patients (62 per cent), serum HPRL was normal, and in one half menstruation was occurring. It follows that elevated HPRL levels should be an indication for extensive investigation and follow-up. Synthetic thyroid-releasing factor was given to 6 selected individuals (5 with elevated basal HPRL levels). An exaggerated HPRL response was found in 3, and a poor response occurred in one of the patients tested. These findings appear to be related to the degree of pituitary reserve and hypothalmic control.

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.

Contraception in teenagers.

This review of the special problems of contraception in teenagers has focused on the need for increased efforts in sex education and family-planning and abortion services for this age group. A clear-cut need for new imperatives in these areas is apparent from the data showing an alarming increase in the incidence and rates of unwanted teenage pregnancy and the increased incidence of teenage sexual activity, as compared with earlier times, and its occurrence at earlier ages than previously. Special counseling, education, physical examination procedures, and care and prescription are required when the physician is considering various methods of contraception for adolescents. In the development of adolescent education for responsible sexual behavior, it behooves physicians to keep in mind that it is the members of this age group, in part on the basis of their reactions to the quality of medical care they receive, who will decide and instill the attitudes toward these important issues in the next generation of Americans.

Analysis of prostaglandins by electron-capture gas chromatography. I. Thermal decomposition of heptafluorobutyrate methyl esters of F1α and F2α☆

Abstract Triheptafluorobutyrate methyl ester (THFB-Met) derivatives are easily prepared from prostaglandins F1α and F2α by successive methylation and heptafluorobutyrylation. The derivatives are reasonably stable during storage, are volatile, and can be detected in the picogram range by electron-capture gas chromatography. Both derivatives exhibit peak broadening or multiple peak formation during gas chromatography at 190°–210°C. Decomposition is independent of the nature of the stationary phase and can be increased by prior heating. Studies with other derivatives suggest that thermal decomposition of the THFB-Met derivatives occuring during gas chromatography involves loss of a heptafluorobutyrate group from the allylic position 15 of the prostaglandins.

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.

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.

Chlorpromazine-Induced Changes in Serum Prolactin in Women with Oligomenorrhea, Amenorrhea, and Pituitary Adenoma

Chlorpromazine (CPZ, Thorazine) administration has been found to result in an increase in peripheral serum levels of prolactin (hPRL) in both men and women. Normal menstruating women were found to have at least a doubling of serum hPRL (100% increase) over basal values within 150minutes of the intramuscular administration of CPZ (0.7mg/kg). Thirty-nine women with oligomenorrhea or amenorrhea with normal or elevated basal levels of serum hPRL were evaluated by this testing modality. Their responses were compared with those of normal women as well as those of 18 women with elevated serum hPRL levels and roentgenographic evidence of pituitary microadenoma. Women with oligomenorrhea or amenorrhea and normal serum hPRL levels generally had a normal response to CPZ (9 of 16 [56.3%]). A smaller percentage of normal responses was found in women with elevated hPRL levels but no overt evidence of pituitary microadenoma (7 of 21 [33%]). Women with elevated hPRL levels and evidence of pituitary microadenoma uniformly failed to have a normal hPRL response following CPZ administration. Although the group with microadenomas did not show a significant hPRL response to CPZ, this test does not unequivocally differentiate between women who have evidence of pituitary adenoma and those who do not. Suggestive, but not conclusive, evidence of hypothalamic dysfunction as the cause of the oligomenorrhea or amenorrhea is presented.

Human placental lactogen: further evidence of placental mimicry of pituitary function.

THE PRESENCE OF one or more proteins in human placental extracts which would stimulate crop sac growth in the pigeon was first demonstrated by Higashi in collaboration with Ito.“-* Somatotropic activity of extracts of the human placenta was also demonstrated earlier by Fukushima.” This note recounts the efforts to identify and purify human placental lactogen (HPL, human chorionic somatomammotropin~ in our laboratory at the Boston Lying-In Hospital and in the Department of Obstetrics and Gynecology, Harvard Medical School. These endeavors are presented as they summarize the importance of research leadership of the chairman of a clinical department, the importance of early financial support for junior investigator, the provision of time for them to carry out such research, the availability of newer techniques at a criticai time in the development of research project, devotion of one’s research technicians, the close proximity of numerous colleagues in allied fields to help in the development of research techniques, and previous preand post-doctoral training in research meth~ology, I had received preand post-doctoral training supported by the Josiah Macy, Jr., Foundation at the Harvard Medical School, Department of Physiology, laboratory of Ernst Knob& where the species specificity of human pituitary growth hormone was discovered, Because of this background, Duncan E. Reid suggested that I embark on a search for the growth hormone-like factor

Reduction of Variability in the Anovulatory Period Following Medroxyprogesterone Acetate Injection by Using Jet Injectors

First 5 different types of jet injectors were tested in 4 mammalian species including man with medroxyprogesterone acetate (MPA). Penetration was generally good with the Dermo-jet Press-o-jet and Hypospray but inadequate with the Syrijet. Because the Dermo-jet allowed administration of a small volume it was employed in further rat studies. Larger aggregates of MPA consistently occurred in fascial planes and within muscle bundles when 5 mg of MPA were given by needle rather than Dermo-jet. In fact in animals needle-injected large deposits of crystals could still be found after animals resumed estrous cycles. Within 24 hours after administration by either needle or Dermo-jet leukocytic infiltration occurred around the microcrystal mass; a mononuclear inflammation occurred afterwards. When 2.5 mg or more of MPA were injected both the first and third cycles after the effects of the drug wore off occurred significantly sooner in the Dermo-jet rats (p less than .01). Women should be more receptive to the form of contraception represented by the Dermo-jet than to the needle injection since there is more certainty as to when menstruation should begin again with the use of the former method. The finer distribution of MPA crystals after Dermo-jet injection may hasten absorption.