R. Herbert Wiebe

The Diagnosis and Therapy of Luteal Phase Deficiency

Between 1973 and 1975, 16 patients evaluated for infertility at Duke University Medical Center were diagnosed as having luteal phase deficiency. A majority had had prior infertility surveys, and the average duration of their infertility exceeded 2 years. The diagnosis was suspected after study of basal body temperature charts and menstrual patterns in more than 80% of the patients. This diagnosis was established by timed endometrial biopsy. The primary method of therapy was supplementation of the luteal phase with progesterone vaginal suppositories. The pregnancy rate after therapy was 50% and pregnancy occurred after a mean of five treatment cycles. The minimal follow-up of patients who failed to conceive was 8 months. To date, the majority of these pregnancies have been completed without complication and the remainder are progressing satisfactorily. Two additional patients developed luteal phase deficiency while taking clomiphene citrate and became pregnant with progesterone supplementation.

Treatment Of Functional Amenorrhea-Galactorrhea With 2-Bromoergocryptine * †

The present study was undertaken to investigate not only the effectiveness of bromoergocryptine therapy in 13 women with amenorrhea-galactorrhea and hyperprolactinemia without evidence of organic pathology, but also to assess the value of pretreatment evaluation in predicting the response to therapy. Sella turcica tomography, base line serum follicle-stimulating hormone, luteinizing hormone (LH), thyroid-stimulating hormone, T4, plasma cortisol levels, and the growth hormone reserve were normal in all patients. The pretreatment administration of LH-releasing factor (LRF) (100 microng subcutaneously) resulted in either a normal or excessive release of LH. On bromoergocryptine therapy, cyclic menses were reintiated in 10 of the women, while conception occurred prior to reinitiation of menses in the remaining three women. The time required for resumption of menses or conception on therapy correlated well with the magnitude of gonadotropin response to LRF. No correlation was seen with pretreatment prolactin levels nor with the degree of suppression of prolactin during bromoergocryptine therapy. In four women the mean prolactin levels during therapy were above normal, and in one patient prolactin levels approached pretreatment values during therapy. The initiation of cyclic menses despite continued hyperprolactinemia may indicate a possible direct effect of bromoergocryptine on hypothalamic LRF secretion as a partial explanation for its therapeutic action. On discontinuation of bromoergocryptine therapy, serum prolactin levels rapidly returned to pretreatment values or higher in all of the patients studied. In contrast to previous studies in which amenorrhea recurred in all patients after discontinuation of therapy, three of our patients maintained cyclic menses despite continued hyperprolactinemia. The recurrence of hyperprolactinemia after discontinuation of bromoergocryptine would indicate a persistent autonomy of the mechanisms involved. Periodic endocrine evaluation will be necessary to substantiate the presence or absence of pituitary microadenoma in these women.

Diagnosis of prolactin-secreting pituitary microadenoma.

Four women with secondary amenorrhea associated with hyperprolactinemia were studied. Baseline hormonal evaluation, including serum FSH, serum LH, TSH, T3, T4, and plasma cortisols were normal. Plain sella turcia x-rays were also normal. Prolactin-secreting pituitary microadenomas were found in all of the patients only after further diagnostic studies were done. These studies included polytomography of the sella turcia, dynamic pituitary testing of growth hormone reserve, ACTH reserve, gonadotropin reserve, and prolactin suppression with L-dopa. The early diagnosis of a small prolactin-secreting adenoma may be possible if several diagnostic criteria are ulilized. The most sensitive techniques available are: (1) polytomography, (2) the magnitude of plasma prolactin evaluation, and (3) the failure of suppression of prolactin secretion with L-dopa. Our findings emphasize the importance of an extensive evaluation of all women with amenorrhea associated with hyperprolactinemia.

The outcome of pregnancy in patients with treated and untreated prolactin-secreting pituitary tumors

Few data document pregnancy risks in patients with prolactin-secreting pituitary tumors, particularly risks relating to the likelihood and severity of increased tumor size. This study presents three groups of women with such lesions. Group 1 consisted of 47 women with transsphenoidal resection who were euprolactinemic postoperatively. Of this group 20 of 22 previously infertile women conceived 25 pregnancies. Group 2 was composed of 17 women who were operated upon but in whom prolactin was still raised (greater than 50 ng/ml) postoperatively and bromocriptine was subsequently used. Seven of these 17 patients were previously infertile, and six of the seven have conceived. In group 3 22 infertile women with small pituitary tumors were not operated upon but received bromocriptine. Eighteen of these patients have achieved 24 pregnancies. Methods of diagnosis, surveillance during pregnancy, and medical and surgical management are presented. Only two patients, both in group 3, developed signs of expanding tumor size in pregnancy.

Spontaneous regression of prolactin-producing pituitary adenomas

Two women evaluated for amenorrhea, galactorrhea, and hyperprolactinemia had radiographic changes of the sella turcica (localized erosion on trispiral tomography) suggestive of a pituitary tumor. Both patients experienced spontaneous regression of apparent prolactin-secreting adenomas with a marked decrease in the quantity of galactorrhea and a reduction of serum prolactin concentrations to the normal range. One patient noted a marked improvement of headaches and spontaneous menses resumed in the other patient.

Amenorrhea: Observations based on the analysis of luteninizing hormone–releasing hormone testing

From 1973 to 1976, 130 patients with symptomatic amenorrhea were evaluated by pituitary gonadotropin response to a subcutaneous injection of luteinizing hormone–releasing hormone (LHRH). These patients were placed in 13 specific disease categories by extensive endocrine evaluation. The LHRH test itself was not used for diagnostic categorization. Test results from these groups of patients were compared with those from 18 early follicular control subjects using logarithms of four baseline and 13 response measurements. Results were as follows: Gonadotropin measurements demonstrated a logarithmic distribution. Each diagnostic category demonstrated multiple significant differences when compared to the control group. Statistical comparisons using logarithms yielded additional significant differences (when n

Prolactin-Secreting Pituitary Microadenoma: Detection and Evaluation * †

Eleven women with secondary amenorrhea associated with hyperprolactinemia were studied. Base line evaluations, visual field determinations, and routine sella turcica x-rays were normal. Prolactin-secreting pituitary microadenomas were found in all of the patients only after further diagnostic studies were carried out. These studies included polytomography of the sella turcica; dynamic pituitary testing of growth hormone reserve, adrenocorticotropic hormone reserve, and gonadotropin reserve; and prolactin suppression with L-dopa. The early diagnosis of a small prolactin-secreting adenoma may be possible if several diagnostic criteria are utilized. The most sensitive diagnostic indices available are (1) polytomography, (2) the magnitude of the plasma prolactin elevation, and (3) the failure to suppress prolactin secretion with L-dopa. Our findings emphasize the importance of an extensive evaluation of all women with amenorrhea associated with hyperprolactinemia.

The effect of hyperprolactinemia on the diurnal variation of adrenal androgens

Morning and evening plasma cortisol, dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) were measured in ten women with hyperprolactinemia secondary to pituitary adenomas and in seven control subjects with cyclic menses and normal prolactin (PRL) levels. Plasma cortisol and DHEA-S levels were comparable in both groups. A diurnal variation for cortisol and DHEA was identified and comparable in both groups. These findings indicate that PRL may not be an important physiologic regulator of adrenal androgen secretion.

Clomiphene citrate: Pharmacologic treatment of hypofertile male

Thirty-two males were treated with clomiphene citrate for a minimum of six months, a maximum of twelve months, or until pregnancy occurred. Among these patients, thirteen pregnancies occurred. Climiphene citrate appears a reasonable pharmaceutical method for management of idiopathic oligospermia.

Steroid secretion and testosterone binding in a woman with an ovarian hilus cell tumor and thyrotoxicosis

Abstract Presented is the case of a 21-year-old woman with an ovarian hilus cell tumor and thyrotoxicosis. Despite massivley elevated of serum testosterone, virilization was lacking and cyctic ovulatory menses were maintained. Hypersecretion of thyroxine and an increased circutating testosterone-estradiol binding globulin (TeBG) resulted In a level of free testosterone lower than expected, thereby perhaps accounting for the negligible androgen effect. Determinations of peripheral and ovarian venous steroids provided the first In vivo evidence for the preferred synthesis of testosterone via the AΔ 5 pathway in a hilus cell tumor. (Am. J. Osstet. Gynecol. 141:535,1981.)