Elías S. Canales

Induction of degenerative changes in uterine myomas by high-dosage progestin therapy

Abstract 1. 1. Continuous administration of 2 mg. estrogen-free norethindrone daily for periods of 1 to 3 months had no effect on uterine myomas in 14 women. 2. 2. Forty-six patients with uterine myomas were treated with a large dose (25 mg. daily) of a highly potent “pure” oral progestin, medrogestone, for periods of 14 or 21 days. Hysterectomies were scheduled at intervals up to 120 days following treatment. Myomas from 40 women at various stages of pregnancy served as a comparison group. Medrogestone therapy for 21 days evoked intense degenerative changes in both small and large myomas exceeding those seen at the end of pregnancy. There was no evidence of cellular proliferation. These changes progressed to fibrosis and hyalinization. Treatment for 14 days produced similar but less consistent changes. It is suggested that brief, intense exposure to appropriate progestational agents has potentialities in the therapy of the myomatous uterus.

Successful Induction of Ovulation with Synthetic Luteinizing Hormone-Releasing Hormone in Anovulatory Infertility

13 women with suspected hypothalamic anovulation were treated with l uteinizing hormone-releasing hormone (LH-RH) by a variety of regimens. 3 women received LH-RH by continuous intravenous infusion equal to 100 mcg LH-RH for 8 hours followed by an acute injection of LH-RH 100 mcg. 10 days later the infusion was repeated without the supplemental injecti on and coitus advised immediately after the end of the 2nd infusion. 10 patients were given LH-RH by injection of 50 mch/day for 10 days. Coitus was indicated every other day from Day 8 of therapy. Presumptive ovulation was determined on each mode of therapy. 2 of the 3 intravenous patients had presumptive ovulation responses wihtout conception. 4 of the 10 injection patients had presumptive ovulation signs and 2 conceived. The 6 remaining injection patients responded with increased estrogens and estrogenic effect on cervical mucus. The results confirm the therapeutic role of LH-RH in certain cases of sterility.

Anovulatory effect of a LHRH antagonist in women

The antagonistic analog of LHRH, NAc-D-p-Cl-Phe(1),(2), D-Trp(3),D-Phe(6), D-Ala(10)-LHRH was administered intramuscularly in a dose of 2 mg to ten normally ovulating women on day 12 of the menstrual cycle. Ovulation was inhibited in six patients, and two more presented an insufficient corpus luteum. No pregnancies were recorded in this series. In those patients who did not ovulate, it was demonstrated that the LHRH analog abolished the midcycle surge of both LH and FSH. Luteolysis evidenced by the rapid decline in progesterone levels was present in 2 cases. Bleeding pattern showed a tendency to delayed menses. The morphological findings in endometrial biopsies of 6 women exhibited mild proliferation. Further research along these lines is necessary for appraisal of this approach to birth control.

Studies on the luteinizing hormone- and follicle-stimulating hormone-releasing mechanism in the testicular feminization syndrome: Hypothalamic-pituitary responsiveness to clomiphene, luteinizing hormone-releasing hormone, gonadectomy, and sexual steroids

Abstract The follicle-stimulating hormone (FSH) and luteinizing hormone (LH) secretory response to various stimuli was studied in 4 adult siblings with the complete form of testicular feminization. Before gonadectomy, the 4 patients had elevated serum levels of both LH and FSH. Clomiphene administered for 7 days did not change the serum levels of gonadotropins. LH-releasing hormone (LH-RH) administration resulted in FSH release above the range observed in normal adult men and women; however, the maximum LH increase was not different from that of normal adults. Gonadectomy elicited a further and significant elevation of both FSH and LH levels. After castration, serum levels of LH and FSH exhibited a further increase following LH-RH administration comparable quantitatively to that before castration. The FSH secretory response to LH-RH was greater than that of LH. The administration of progesterone alone to the 4 patients already castrated did not result in any major change in the serum levels of FSH and LH. Estrogen administration decreased the high levels of gonadotropins. The relative decrease for FSH was greater than for LH, and, when progesterone was given following 4 weeks of estrogen treatment, an increase in the serum levels of LH was found; there was also a small increase in FSH concentration. It is concluded from this study that in testicular feminization: (1) There is a partial gonadal feedback control of both FSH and LH secretion; (2) hypothalamic receptors are not sensitive to the stimulatory effect of clomiphene; (3) there is an unusually large amount of FSH released by the pituitary after intravenous LH-RH; (4) FSH and LH secretion are readily suppressed by estrogen administration; (5) there is a positive feedback effect of progesterone upon serum gonadotropins in estrogen-primed castrated patients with testicular feminization.

Pituitary responsiveness to synthetic luteinizing hormone-releasing hormone during pregnancy: Effect on follicle-stimulating hormone secretion

Abstract Thirteen pregnant women were given synthetic luteinizing hormone-releasing hormone (LH-RH) by a single intravenous injection. Serum concentrations of follicle-stimulating hormone (FSH) were measured by radioimmunoassay. A significant rise in FSH was found after LH-RH administration in 10 of the 13 patients; however the response was very variable in each case. The maximum increase in the serum levels of FSH above the base line remained constant with the advancement of pregnancy. The present study confirms that the pituitary gland responds to LH-RH administration with the secretion of FSH despite the high levels of sex steroid and chorionic gonadotropin during pregnancy.

Pituitary FSH and LH reserve in women with isolated gonadotropin deficiency.

Six women with isolated gonadotropin deficiency were stimulated with 50 μg of synthetic luteinizing hormone-releasing hormone (LH-RH) and their response was compared with that obtained from 10 eumenorrheic women. Patients with hypogonadotropic hypogonadism had low serum LH levels and normal or near

EFFECT OF CLOMIPHENE ON PROLACTIN SECRETION AND LACTATION IN PUERPERAL WOMEN

Clomiphene citrate treatment neither inhibited milk secretion nor had a suppresive effect on serum prolactin levels in 10 puerperal women.

Further observations on postpartum ovarian refractoriness: effect of gonadal stimulation in women receiving bromocryptine.

It has been reported previously that the administration of human menopausal gonadotrophins (HMG) to lactating and non‐lactating women from day 5 to day 9 postpartum elicited no significant elevation of urinary oestrogens or serum oestradiol within 15 days after delivery. In order to study further the role of prolactin on this ovarian refractoriness, five women receiving 7.5 mg of bromocryptine (CB‐154) daily were given HMG at a dose of 300 iu per day, from day 5 to day 10 postdelivery. In all women serum oestradiol and urinary oestrogens showed no significant elevation within the 2 weeks after delivery. Serum prolactine was elevated in all cases and fell to normal nonpregnant levels immediately after CB‐154 was administered. The suggestion that prolactin may possess antigonadotrophic activity at the ovarian level is not supported by the data presented here. The deficient ovarian response to gonadotrophin stimulation could be due to either the intraovarian effect of the high amounts of circulating steroids produced during gestation or to some unknown mechanism.

Long-Term Administration of Thyrotropin-Releasing Hormone and its Effect on Gonadotropin Secretion in Eumenorrheic Women

Thyrotropin-releasing hormone (TRH) was administered orally in doses of 60 mg/day to six women for two consecutive menstrual cycles. Daily serum samples were obtained for radioimmunoassay of luteinizing hormone, follicle-stimulating hormone, prolactin (PRL), and 17beta-estradiol secretory response. TRH was ineffective in interfering with normal gonadotropin and estradiol secretion, and failed to inhibit ovulation. The length of the luteal phase was not affected by TRH in the two cycles of treatment as demonstrated by basal body temperature, pregnanediol excretion, and endometrial biopsy. Long-term TRH administration induced an elevation of PRL serum levels that were not persistent and showed wide spikes. From these studies it is concluded that oral TRH at a dosage of 60 mg/day is unable to modify gonadotropin secretion and ovarian responsiveness in normally menstruating women.

Successful induction of ovulation with synthetic luteinizing hormone-releasing hormone in anovulatory infertility

13 women with suspected hypothalamic anovulation were treated with l uteinizing hormone-releasing hormone (LH-RH) by a variety of regimens. 3 women received LH-RH by continuous intravenous infusion equal to 100 mcg LH-RH for 8 hours, followed by an acute injection of LH-RH 100 mcg. 10 days later the infusion was repeated without the supplemental injecti on and coitus advised immediately after the end of the 2nd infusion. 10 patients were given LH-RH by injection of 50 mch/day for 10 days. Coitus was indicated every other day from Day 8 of therapy. Presumptive ovulation was determined on each mode of therapy. 2 of the 3 intravenous patients had presumptive ovulation responses wihtout conception. 4 of the 10 injection patients had presumptive ovulation signs and 2 conceived. The 6 remaining injection patients responded with increased estrogens and estrogenic effect on cervical mucus. The results confirm the therapeutic role of LH-RH in certain cases of sterility.