Samuel H. Geist

The use of estrogens in the treatment of dysuria and incontinence in postmenopausal women

Abstract The study reported here stems from the observation that a number of women with disorders of micturition, consisting of urinary frequency, urgency, and incontinence, experienced relief of these symptoms while being treated with estrogens for the usual menopausal complaints. In order to determine the relationship of the estrogen therapy to the amelioration of the urinary symptoms, a group of postmenopausal patients with urgency, dysuria, and stress incontinence were selected for study and treatment.

Diffuse luteinization of the ovaries associated with the masculinization syndrome

Abstract The syndrome of masculinization in the female, attributed to pituitary basophilism or adrenal cortical lesions, usually includes regressive changes in the ovaries. At times, however, as evidenced by the two cases described in this report, there may be bilateral ovarian enlargement, due to excessive perifollicular proliferation and luteinization of the theca cells and diffusely scattered luteinized cells within the ovarian parenchyma. The ovrian effects are suggestive of increased gonadotropic stimulation and are probably secondary. It does not appear that they are responsible for the production of the masculinization syndrome. In the clinical investigation of virilism the presence of an ovarian enlargement has been and should be regarded as suspicious evidence of a possible arrhenoblastoma or adrenal rest neoplasm of the ovary. In view of this report, a third possibility exists, namely, enlargement of the ovary due to diffuse luteinization. It may be possible to decide, at operation, by incision of the ovaries, whether or not tumor is present. If, in young patients, tumor can unequivocally be ruled out by this device, one or both ovaries may be left in situ.

Theca cell tumors

Abstract The anatomic and histologic characteristics of theca cell tumors are described, together with their distinctive clinical and hormonal features. Descriptions are given of six cases illustrating variations from the more benign fibroma type to the highly cellular and malignant type. A correlation is made between the presence of hormonal changes and the presence of intracellular, doubly refractile fat containing cholesterol and cholesterol esters. It is suggested that some of the ovarian neoplasms previously diagnosed as fibromas or fibrosarcomas may on further investigation prove to be of theca cell origin.

Experimental biologically active ovarian tumors in mice

Abstract X-ray irradiation of mice at puberty results in the production of two types of ovarian tumors: tubular adenomas derived from the surface epithelium and parenchymal lutein tumors. The parenchymal lutein tumors alone exhibit hormonal activity expressed in proliferative changes in the endometrium and vaginal mucosa. Histologically, these tumors are composed of granulosa and theca cells with varying degrees of luteinization. They are entirely comparable to the granulosa cell tumor and its excessively luteinized variant, the Lecene tumor, and the theca cell tumor of the human ovary. The luteinized ovarian tumors in mice are derived from the undifferentiated parenchyma. While the theca interna cells participate in the early proliferation and luteinization, the mature granulosa cells play no role in the genesis of these neoplasms. The histogenesis of the analogous human tumors may well be identical.

Excretion of Pregnandiol in Women with Virilism

Butler and Marrian 1 in reporting the isolation of a steroid compound pregnane-3-17-20-triol, from the urine of 2 women with virilism caused by “enlarged adrenals,” also noted the presence of “appreciable amounts of pregnandiol.” Venning, Weil and Browne 2 later reported the finding of considerable amounts of sodium pregnandiol glucuronidate (12 mg to 30 mg per day) in 2 cases of virilism, one of which was subsequently found to have an adrenal cortex carcinoma and, the other, adrenal cortex hyperplasia. During the past 2 years, we have been performing pregnandiol excretion studies in women with the arrhenomimetic (virilism) syndrome. In the present communication, we wish to report the results of these studies. Methods and Materials. A total of 7 cases was studied. These consisted of 2 cases proven by operation to be adrenal cortex carcinomas and 5 cases of amenorrhea and hypertrichosis of undetermined etiology. Sodium pregnandiol glucuronidate determinations 3 were performed on single 24-, 48-, or 72-hour specimens, for periods varying from 6 to 32 days. Results. Pregnandiol Excretion in Patients with Adrenal Cortex Carcinoma. In the 2 patients in whom adrenal cortex carcinomas were found, the pregnandiol excretion varied in one from 9 to 20 mg per day and, in the other, from 12 to 18 mg per day. In one patient (I.E.), in whom it was possible to obtain post-operative urines, these were found to contain no detectable amount of pregnandiol after removal of the tumor. Pregnandiol Excretion in Patients with Arrhenomimetic Syndrome (without adrenal cortex carcinoma). In the 5 cases in this group, X-rays of the adrenals after intravenous pyelogram and peri-renal insufflation failed to reveal any evidence of adrenal tumor or enlargement. Two of these (E.W. and T.S.) were explored surgically without revealing any evidence of adrenal neoplasm.

Are Estrogens Carcinogenic in the Human Female

A case report of a 52-year-old patient gravida 3 and para 2 in whom menstruation had ceased 2 years previously is presented. Small uterine fibroids were present. She received 40000 RU of alpha-estradiol-benzoate in less than 2 months. Several months later spontaneous uterine bleeding occurred. A small cervical polyp was removed. The endometrium at that time showed areas of proliferation with other areas of hyperplasia. In a period of about a month she received 234000 RU of alpha-estradiol-benzoate and 65 mg of progesterone im. Before the progesterone was given an endometrial biopsy revealed advanced proliferation with areas of cystic hyperplasia. After progesterone therapy the endometrium showed proliferation and secretory phenomena. 6 months later evidence of estrogen deficiency was present and a pellet of 25 mg of crystalline alpha-estradiol was implanted sc. Her symptoms subsided. 7 months later menopausal symptoms recurred. The implantation site was excised after an additiona l 2 months. Endometrial and vaginal biopsies then showed endometrial regression and evidence of estrogen deficiency in the vaginal biopsy. At this time 29 mg of crystals of alpha-estradiol-benzoate were implanted. After 6 weeks uterine bleeding occurred and intermittent spotting persisted for 6 weeks. Then endometrial biopsy showed advanced proliferation and dilated glands. A later biopsy showed a variable pattern with some atypical glands. 1 month later a diagnostic curettage under anesthesia was done. A diagnosis of adenocarcinoma was made on the tissue removed. A hysterectomy was then done. The uterus contained 2 small myomas and an endometrial polyp but no carcinoma metaplasia or cellular atypica was found. A benign endometrial condition was believed to have been present although consulting pathologists who reviewed the slides were divided as to whether an early carcinoma had been present.

The treatment of dysmenorrhea with testosterone propionate

The subject of dysmenorrhea has engaged the attention of numerous investigators and an extensive literature has accumulated on the subject. The etiology of this distressing condition, however, is still obscure and its treatment still unsatisfactory. Reviews of the various hormonal theories of the cause of dysmenorrhea have recently been published by several authors.1–4 Briefly, there are three current theories as regards the etiology of dysmenorrhea: (a) Deficiency in progesterone, permitting of the unopposed action of estrogenic hormone upon the uterine muscle; (b) excessive estrogen production resulting in hypermotility of the uterine musculature; and (c) excessive progesterone activity.5 None of these theories is, however, adequately supported by controlled experimental studies. The present communication deals with the treatment of dysmenorrhea with male hormone (testosterone propionate). The rationale for this form of therapy is based on the observation that testosterone counteracts certain of the physiologic effects of the estrogens in animals and human beings.Abstract The subject of dysmenorrhea has engaged the attention of numerous investigators and an extensive literature has accumulated on the subject. The etiology of this distressing condition, however, is still obscure and its treatment still unsatisfactory. Reviews of the various hormonal theories of the cause of dysmenorrhea have recently been published by several authors. 1–4 Briefly, there are three current theories as regards the etiology of dysmenorrhea: (a) Deficiency in progesterone, permitting of the unopposed action of estrogenic hormone upon the uterine muscle; (b) excessive estrogen production resulting in hypermotility of the uterine musculature; and (c) excessive progesterone activity. 5 None of these theories is, however, adequately supported by controlled experimental studies. The present communication deals with the treatment of dysmenorrhea with male hormone (testosterone propionate). The rationale for this form of therapy is based on the observation that testosterone counteracts certain of the physiologic effects of the estrogens in animals and human beings.

The variability of menstrual rhythm and character.

In examining the variability of menstrual rhythm and character a careful study of 200 cases was conducted. With great detail the exact days of each menstrual period for an entire year were ascertained. These cases represented women who were being observed for such conditions as cystorectocele or retroversion. These women were not actually ill; they were without gynecologic disease. The most striking finding was the fact that the menstrual period failed to recur regularly on any specific day. In very few instances the periods occurred on the 28th day for 9 of the 12 months. For 6 or 7 months of the year the onset of the period was marked by extreme irregularity varying from 28-40 days and then suddenly for the remainder of the year a so-called normal 29 day cycle. There was also a distinct though not so marked variation in the duration of the flow. In 115 of the 200 cases the periods for the entire year lasted exactly 4 days; in 50 for 5 days; in 18 for 6 days; in 9 for 7 days; in 3 for 8 days; and in 4 for 12 hours. In several cases where the period lasted 4 days a single period during the year would last but for 3 days or occasionally extend to 5 days. In the cases that normally lasted for 5 days the were several instances where the duration was only 4 days for l 2 or even 3 periods in the year and an occasional period that lasted 6 days. The mode of onset and intensity of a period also presented differences. The character of onset varied irrespective of the interval or duration. In a number of women the mode of cessation varied. These observations suggest a wide range of variability in the actual concept of the normal menstrual function.

Effect of Testosterone Propionate on Glycogen Content of Human Vaginal Smears

Summary A method of demonstrating simultaneously the presence of glycogen and the morphologic characteristics of the desquamated cellular elements of the vaginal mucosa is presented. The glycogen in the desquamated vaginal epithelial cells of normally menstruating women can be made to disappear by administering adequate amounts of testosterone propionate. The disappearance of the glycogen is apparently dependent upon the production of atrophic changes in the vaginal mucosa since the first effect of the testosterone propionate is the disappearance of the squamous epithelial cells and their replacement by cells from the deeper layers of the mucous membrane. Coincident with this change in the size of the cells, the glycogen begins to decrease steadily and finally vanishes completely. Restoration of the glycogen in the smears parallels closely the reappearance of the normal vaginal epithelium. The question arises as to the mechanism of this regression in the smear and the disappearance of the glycogen. There is experimental evidence indicating that androgens negate the biologic effect of estrogens. 1-3 It is, therefore, conceivable that the testosterone propionate in the cases reported here inactivated the estrogen formed in the individual and, as a result, atrophy of the vaginal mucosa occurred with loss of cornification and consequent disappearance of glycogen. It seems likely, however, that the regressive changes induced in the smear are also the end results of inhibition of the gonadotropic hormone formation of the hypophysis resulting in suppression of the follicular ovarian cycle. That the testosterone propionate probably inhibits the hypophysis is suggested by the following observations: (a) the excessive gonadotropic hormone excretion in a human female castrate can be suppressed with testosterone propionate; 5 (b) ovulation can be similarly inhibited in monkeys; 6 (c) menstruation can be inhibited and the estrogen and progesterone effects in the endometrium of cyclical human females can be suppressed by administering adequate amounts of testosterone propionate. 7

Postmenopausal endometriosis: A case report and review of the literature

Abstract 1. 1. Theories of the origin of endometriosis are reviewed and the pathophysiologic role of estrogen stimulation is discussed. 2. 2. A series of 203 cases of adenomyosis is presented, of which 23 were in women past the climacteric. An additional case is studied and reported. 3. 3. The origin and fate of such tumors in the postmenopausal woman are discussed.