Progestational Therapy Research Articles

The Effect of Treatment with a Low-dose Progestagen (Lynestrenol) on Hormonal Cytology

The effect of continuous, low-dose progestagen therapy on endogenous oestrogen production and ovulation in women, was investigated in terms of vaginal cytology. The phase contrast method was used to establish the karyopknotic index from 482 smears from patients using lynestrenol 0.5 mg for oral contraception. The results are presented as the mean of karyopyknotic indices, with standard deviation and standard error of the mean, scored over each three day period of the menstrual cycle, and, in the case of delayed menstruation, over longer periods throughout the protracted cycle. Graphically, the results are shown as average levels compared to controls. Our results show that in patients who have used the preparation for a maximum of three months, cyclic oestrogen production varies only slightly, the mean being within the lower limit of normal and suggesting FSH suppression. In patients who use the preparation for longer periods, the karyopyknotic index becomes similar throughout the cycle to that of controls, being clearly biphasic and generally suggestive of ovulation. In the first group, delayed menstruation seems to be caused mainly by transient FSH suppression. When it occurs in the group treated over a longer period, the disorder appears to be caused by a normo- or hyperoestrogenic, anovulatory condition, due initially to LH suppression with FSH supression setting in later, if the disorder persists longer.

Endolymphatic stromal myosis in two patients on progestagen therapy

Two patients suffering from menometrorrhagia were treated with progestational agents and were subsequently found to have massive endolymphatic stromal myosis. Both are alive and well 3 and 6 years following surgical treatment which was supplemented by radiation in one of them. Although a causal relationship between the progestational medication and the development of endolymphatic stromal myosis cannot be established in these cases, it is conceivable that these hormones stimulated the growth of the lesions.

Carcinoma of the cervix with cylindromatous features believed to arise in mesonerphric duct

A detailed description of the clinical and morphological aspects of a case of carcinoma of the cervix arising from mesonephric duct remnants is presented, and the literature pertaining to these rare tumors is discussed. At the time of initial surgical treatment the tumor was confined to the cervix; however, eventual metastatic dissemination to the bony and soft tissues of the pelvis, the lungs, and the lower vertebral column resulted in the patient's death 8 years later. The tumor appeared refractory to further attempts at treatment with radiation, progestational therapy, and variety of chemotherapeutic agents. The observation of a focal cylindromatous growth pattern, not previously described in tumors of this type, is presented.

The treatment of advanced endometrial cancer with hydroxyprogesterone caproate

In 314 women with progressing advanced adenocarcinoma of the uterine corpus (endometrial cancer) no longer responding to established anticancer measures, hydroxyprogesterone caproate (1.0 or more g/wk intramuscularly for 4 or more wk) induced in 37.0% an objective response (averaging 20 mo in duration) consisting of regression in 30.2% and arrest of the disease in 6.8%. These responders survived an average of 27 mo, over four times as long as the nonresponders. The incidence of responders was significantly greater in patients with slowly growing tumors, in those treated for 12 or more wk, and for patients with rapidly growing tumors in the younger women. The objective response rate was not influenced significantly by obesity, by the amount of hydroxyprogesterone caproate per week, or by the discontinuation of the progestational therapy during an objective response. Other findings suggest that the efficacy may have been decreased in Negro women, increased in women with no prior radiation but with cancerous involvement only in the nonpulmonary areas, increased in women with prior radiation and metastatic lesions limited to the pulmonary area, decreased by prior radiation therapy in women with nonpulmonary lesions but not in those with pulmonary metastases, and increased in women given radiation concomitantly but not influenced in those given other anticancer therapy simultaneously. After 13 yr of observation, 13.4% of the women appeared to be potentially “cured”; no significant distinctive pattern of characteristics could be discovered by which a woman who achieved the “cured” status could have been selected in advance. These factors concerning efficacy and potential “cure” need further study. Hydroxyprogesterone caproate (up to 7.0 g/wk) was safe and well tolerated; undesirable manifestations occurred infrequently.

Transplacental carcinogenesis by stilbestrol.

This editorial argues the cause-and-effect relationship between in utero exposure to diethylstilbestrol (DES) and incidence of vaginal adenocarcinoma among young women. It is conjectured that the mechanism by which DES induces tumors is a result of transplacental carcinogenesis; i.e., DES causes a malignant change in any fetal cell of future vaginal tissue, resulting in a genetic defect which may not be realized until puberty, when endogenous hormone production acts as a promoter of the malignancy initiated by DES exposure during gestation. If this theory is correct, local progestational therapy may arrest future adenocarcinoma cases. Though it is obvious that DES therapy must be avoided in the future in the population of pregnant women, of more concern is the presence of residual DES in foodstuffs, particularly livestock meat. A ban of such diet supplementation of human foodstuffs is called for.

Progestational therapy and metastatic adenocarcinoma of the body of the uterus.

Using progestational therapy a marked regression occurred in a patient with pulmonary and vaginal metastases developed from an earlier adenocarcinoma diagnosed about 8 years earlier of the uterine body. The patient received dimethisterone at 300 mg/day orally in divided doses for about 1 year the dosage because of the absence of symptoms and the general state of well-being was then reduced to 200 mg/day. The patient was last examined about 6 months later; no side effects were seen from the dimethisterone therapy. The disappearance of regression of pulmonary metastases has been observed only rarely in the literature.

Pituitary-adrenocortical effect of short- and long-term progestational therapy

With the metyrapone (SU-4885) test, 50 patients on short- and long-term progestational therapy were investigated for the possible inhibitory effect of these compounds on pituitary ACTH production. Result of the tests (comparison of plasma corticoids, plasma desoxycortisol, urinary 17-ketogenic steroids, and urinary 17-ketosteroids before and after the metyrapone test) indicated that progestational agents used in this study in either form (combined versus sequential) were all capable of this inhibitory effect and statistically no particular agent appeared to be more responsible than others. New hypotheses as to the mechanism of pituitary ACTH suppressive effect of these compounds are postulated and new theories as to the lack of development of frank adrenocortical deficiency are described.

Morphology of the cervix in women treated with synthetic progestins

A study of cervical morphology was carried out in 5 groups of subjects: (1) 104 women using oral contraceptives for 9 months or longer; (2) 43 women receiving continuous, usually high-level oral progestational therapy with little or no estrogen; (3) 20 women dying of accidental deaths; (4) 30 women dying in the third trimester of pregnancy; and (5) 24 women with endometrial hyperplasia. The patients on oral contraceptives were studied by multiple biopsies, while in the others the entire cervix was examined.Cervical glandular hypersecretion and stromal edema increased with the exposure to progestational influences. With continuous progestin dosage or in pregnancy, an increase of pronounced squamous metaplasia was noted. There was no evidence of an increase of epithelial changes in the cervix of women receiving contraceptive therapy, as compared to the other groups.

BOOK REVIEWS

Book reviews in this article: “Medical, Surgical and Gynecologic Complications of Pregnancy.” By J. J. Rovinsky and A. F. Guttmacher. “Caesarean Section Scars.” By L. O. S. Poidevin. “The Effects of Education for Childbearing on the Mother's Well‐being.” “Marriage and First Pregnancy.” By E. R. Goshen‐Gottstein. “Elettrofonocardiografia Prenatale, Fisiopatologia e Clinica.” By G. Brigato, G. Franco, F. Cipani, and G. Abelli. “Care of the Newly Born Infant.” By W. S. Craig, in collaboration with M. F. G. Buchanan, G. M. Lewis, J. M. Littlewood, and Miss M. Pattullo. “Backache in Women.” By E. Schleyer‐Saunders. “Progestagen Therapy.” By Maxwell Roland, in collaboration with N. Applezweig, M. J. Clyman, A. Decker, and W. B. Ober. “Research on Steroids.” Transactions of the First Meeting of the International Study Group for Steroid Hormones. Edited by C. Cassano.

THE MANAGEMENT OF THREATENED ABORTION BY PREGNANEDIOL ESTIMATION AND VAGINAL CYTOLOGY.

Summary: Forty‐four patients with threatened abortion have been investigated for progestational activity by pregnanediol excretion and lateral vaginal smears. The prognostic accuracy of both methods of estimation was similar. When both pregnanediol and smear reports were normal over 80% of pregnancies reached viability. When either report indicated severe progesterone deficiency no pregnancy reached viability. It is suggested that the lateral vaginal smear should be used as an index in most cases of threatened abortion if progestational therapy is considered.

Selection of Patients in Early Pregnancy for Progestational Therapy

Selection of Patients in Early Pregnancy for Progestational Therapy

Adolescent Dysfunctional Bleeding

Functional uterine bleeding in adolescence is readily responsive to hormonal therapy. Newer progestational agents will arrest bleeding rapidly. Subsequent to arrest of bleeding, a withdrawal period should be expected. Cyclic progestational therapy should then be continued for several months or years, if necessary, until ovulatory menstrual cycles are re-established. Such month-to-month regulation of uterine bleeding in adolescent girls offers the greatest opportunity to salvage their reproductive capacity and establish normal menstrual function.