Estrogen-progesterone Therapy Research Articles

Surrogate Embryo Transfer Combined with Estrogen-Progesterone Therapy in Monkeys Implantation, Gestation, and Delivery Without Ovaries

Pregnancy Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.

Surrogate Embryo Transfer Combined With Estrogen-Progesterone Therapy in Monkeys

The collection of in vivo fertilized embryos by lavage of the normal donor's uterotubal lumens and transfer of these surrogate embryos to the uterotubal environs of long-term castrate female monkeys is described. Sequential estrogen-progesterone replacement therapy that mimics the natural ovarian-menstrual cycle was administered to the recipients, causing the development of proliferative and secretory endometrium to accommodate the perinidatory events leading to successful placentation and embryogenesis. Retrograde irrigation of the uterotubal lumens of 23 normal intact donors was performed three to four days after the estimated time of ovulation, coitus, and fertilization. Of the 17 embryos or eggs collected, some were apparently healthy, as assessed by microscopic inspection, whereas others were obviously degenerating. Eleven surrogate embryos were transferred to steroid-treated, long-term castrate female recipients; four viable pregnancies were detected by measurement of chorionic gonadotropin, all concluding with uneventful deliveries of normal live neonates at term. These findings demonstrate the feasibility of establishing and maintaining normal pregnancy by combining surrogate embryo transfer with an exogenous steroid hormone regimen, even in the complete absence of ovarian function. The clinical implications of these primate studies may be far-reaching because they indicate new potential for childbearing by otherwise infertile or sterile women who have a competent uterus but lack the hormonal milieu provided by ovarian follicular maturation and corpus luteum function in the normal menstrual cycle.

Surrogate embryo transfer combined with estrogen-progesterone therapy in monkeys. Implantation, gestation, and delivery without ovaries

Surrogate embryo transfer combined with estrogen-progesterone therapy in monkeys. Implantation, gestation, and delivery without ovaries

Turner's syndrome: Results of estrogen therapy

Annual endometrial biopsy had been advocated for patients with Turner's syndrome. The practicality of using this procedure on patients with no symptoms of abnormal bleeding has been questioned; this study attempts to answer this issue. Charts of patients with Turner's syndrome from the Cleveland Clinic for the period 1951-75 were reviewed. A criteria was established for inclusion of patients in the study. 34 of 43 women who met the criteria returned for the follow-up and were given pelvic exam, Pap smear, and endometrial biopsy by Vabra aspiration. Of the 43 patients given substitution therapy, 13 were taking estrogen alone; 24 were on estrogen-progesterone therapy, and 6 had stopped taking estrogen (Table 1). The presenting symptom in all cases of endometrial adenocarcinoma was abnormal bleeding (menorrhagia or menometrorrhagia), suggesting a change from previous menstrual patterns. At high risk for developing endometrial carcinoma at an early age was patients with dysgenesis who were receiving estrogen replacement therapy. The results of this study suggest that annual endometrial sampling is not necessary for patients with Turner's syndrome. It is recommended, however, that an annual examination and a Pap smear of an endocervical specimen be performed. Should there be any sign of menstrual aberration, endometrial biopsy or dilatation and curettage should be done. The importance of careful follow-up should also be impressed on patients who are on estrogen therapy; not more than 1 year's supply of estrogen should be given to such patients.

343 ENDOMETRIAL CARCINOMA AND HYPERPLASIA IN PATIENTS WITH GONADAL DYSGENESIS RECEIVING ESTROGEN-PROGESTERONE THERAPY

Fifty-one patients with gonadal dysgenesis receiving estrogen-progesterone replacement therapy for periods of six months to twenty years were studied. Endometrial biopsies or dilatation and curettage were obtained in forty-seven patients. One patient on diethylstilbesterol had atypical endometrial hyperplasia which progressed to adenoepidermoid carcinoma. Six patients had benign cystic hyperplasia. Endometrial abnormalities occurred in patients with a duration of estrogen therapy greater than 3-5/12 years and who received a total lifetime estrogen dose exceeding 2500 mg of conjugated estrogen or its equivalent. Five patients who developed endometrial hyperplasia had taken cyclic estrogen-progesterone therapy; the sixth took unopposed estrogen therapy. Total nuclear estradiol binding was measured in six patients with Turner Syndrome and nine control women. Two of the Turner patients had endometrial hyperplasia. Nuclear binding in these two subjects did not differ from that of the other patients with Turner Syndrome. Nuclear binding in the Turner patients (range 3-101/DPM ng DNA) was not different from that of nine control women at comparable stages of the menstrual cycle (34-429 DPM/ng DNA). Cytoplasmic binding of estradiol was not different in two patients with Turner Syndrome with hyperplasia from the four without.

Estrogen-progesterone therapy: A new approach in the treatment of habitual abortion: Studies indicating its rationale in 24 treated cases

1.1. A study was made of a group of 24 patients with habitual abortion who were treated with estrogen and progesterone.2.2. These patients had gone through a total of 80 previous pregnancies from which there had resulted only 7 living babies (9 per cent). There had been 52 abortions, 18 miscarriages, 2 stillbirths, and one premature live birth in which the infant did not survive.3.3. Fifty-four per cent of this group had no difficulty in becoming pregnant, 8 per cent were of diminished fertility, and 38 per cent were of poor fertility.4.4. In none of these patients were there any pelvic abnormalities or systemic diseases which would influence abortion.5.5. In only one patient was the basal metabolic rate diminished.6.6. Two patients had Rh incompatibilities (Rh-negative wife and Rh-positive husband). One of these delivered a normal living baby and the others aborted; in neither case did Rh antibodies develop.7.7. Examination of the endometrium obtained by biopsy or curettage was available in 11 cases before the present pregnancy. Good secretory function was noted in 7 cases, impaired secretory function in 2, and an interval endometrium in two.8.8. Urine hormone assays were made in 15 cases prior to the onset of pregnancy. Urine gonadotropin assays made at the mid-cycle were normal in 87 per cent. Urine estrogens made at the mid-cycle and during the third week of the cycle were diminished in 67 per cent, while low or absent pregnandiol values were obtained in 53 per cent. Since these studies were made in only one cycle, their significance is limited.9.9. Hormone assays consisting of urine pregnandiol determinations, serum estrogens, and serum gonadotropins were made early in pregnancy in 19 cases. In almost all of the cases one or more additional assays were made and in 3 cases monthly assays were done.On the initial assay 95 per cent of the cases showed normal serum gonadotropins. Seventy-nine per cent had diminished serum estrogens and 83 per cent had diminished pregnandiol titers. In 13 of the 19 cases studied, both estrogen and pregnandiol were diminished. These findings indicate a deficiency of the corpus luteum during the early weeks of gestation and an inadequacy of the placenta to take over its functions.10.10. Many of these patients had been unsuccessfully treated in previous pregnancies with progesterone, thyroid, and vitamin E.11.11. During the present pregnancy all patients were treated by the injection of progesterone, 10 mg., and alpha-estradiol benzoate, 10,000 rat units, given together two or three times weekly. This treatment was generally continued to the period of viability or later.12.12. There was fetal salvage of 16 babies, or 67 per cent. There were 15 full-term live births (with one neonatal death due to congenital abnormalities), 3 premature live births of which 2 survived, 2 miscarriages, and 4 abortions.

Effects of estrogenic therapy upon ovarian function: II. When employed during anovulatory cycles

T HE ability of adequate estrogenie therapy to transform normal progestational cycles of women to estrogenic (and presumably anovulatory) ones has been verified in the preceding communication.l It would appear most unlikely that therapy of this kind and order is capable of restoring normal progestational cycles in women with ovarian failure of anovulatory type. An investigation, however, of the end results of estrogenic therapy in association with anovulatory failure seemed advisable for several reasons : (1) to confirm or to deny the dictum that, regardless of our ability to substitute for the endocrine deficienry of ovaries with intrinsic ovarian principles no salvage of physiologic functions, i.e., return of the fertile state, results; and (2) to confirm or to deny the theory that the salvage of ovarian function which has been described as following cyclic estrogenprogesterone therapy in a large group of women with prolonged or excessive estrogenic bleeding results solely from t,he estrogenic fraction of the therapeutic schedule. The commercial availability of a cheap, potent,, and orally active nonhormonal est,rogen (diethylstilbestrol) requires a clear definition of the role of estrogens in the treatment of ovarian failure. Methods Sixteen patients whose ages ranged from 15 to 35 years (average age 21.6 years) were selected for this investigation. These patients had presumed anovulatory ovarian failure predicated upon the occurrence of episodes of estrogenic bleeding. The bleeding cycles were commonly irregular and often of prolonged duration. Each patient selected had received from one to three endometrial biopsies prior to initiation of therapy. Two hormonal estrogens, estriol glucuronidet and estradiol in the form of its benzoatet and dipropionate,§ and an nonhormonal estro*Part I of this article was included in the February issue. ?Estriol glucuronide (emmenin) supplied by Ayerst, Montreal, Canada. McKenna and Harrison.

Subjective Symptoms and Therapeutic Response in the Control of Estrogen-Progesterone Therapy in Menstrual and Reproductive Disorders

It has long been obvious that the two ovarian hormones estrogen and progesterone have a definite relationship to each other and to menstrual and reproductive function. An antagonistic relationship between estrogen and progesterone was first suggested by Smith and Smith in 1931 (1). Prior to the presentation of a gravimetric method for the estimation of urinary pregnandiol by Venning (2) in 1937, endometrial biopsy was the only means available for the estimation of progesterone activity. Wilson, Randall and Osterberg (3) have presented evidence indicating that endometrial changes do not provide an accurate index to the variations of urinary pregnandiol levels. This observation would seem to indicate that endometrial changes are of qualitative rather than quantitative significance. Lack of quantitative means for the determination of progesterone activity has undoubtedly been responsible for the paucity of considerations of estrogen and progesterone relationship in the literature. Theories for estrogen and p...