Testosterone and 17 beta-oestradiol secretion of the human ovary. I. normal young women, and premenopausal women with endometrial hyperplasia.

Testosterone and 17 beta-oestradiol were determined in blood obtained from the ovarian veins of 26 women, 16 of whom were young and regularly ovulating and menstruating, and 10 of whom were premenopausal with uterine bleedings and endometrial hyperplasia. The concentrations of these two hormones in the cubital veins of the premenopausal women were also determined. It was found that the concentrations of the two hormones were not significantly greater in the premenopausal women than in the control group of young normally ovulating and menstruating women in the periovulatory phase of the menstural cycle, but that the ovarian secretion rates of both hormones, particularly of testosterone, were considerably greater in the premenopausal women. In these women the concentrations of both hormones were significantly lower in the cubital veins than in the ovarian veins. The conclusion is that the augmented oestrogenic effect on the endometrium and on other target organs of premenopausal women with endometrial hyperplasia may be due not only to an increased ovarian secretion rate of estradiol, but also and more specifically to an increased ovarian secretion rate of testosterone, and to the rapid vonversion of this hormone into oestradiol in the periphery.

Testosterone and 17 beta-oestradiol secretion of the human ovary. II. normal postmenopausal women, postmenopausal women with endometrial hyperplasia and postmenopausal women with adenocarcinoma of the endometrium.

A study of the concentration of testosterone and of 17 beta-estradiol in blood drawn from the ovarian and cutal veins of normal oestrogen-deficient postmenopausal women and of postmenopausal women with signs of oestrogen activity, and the subsequent computation of the ovarian production rates of these two hormones, show that in the latter group of women there is a high ovarian secretion of testosterone. The theory is advanced that this ovarian-secreted testosterone is rapidly converted into 17 beta-oestradiol, and that, by thus increasing the levels of circulating oestrogens, ovarian-secreted testosterone contributes, albeit indirectly, to endometrial hyperplasia and possibly to endometrial carcinoma.

Plasma gonadotropin response to D-Ala6-LH-RH propylamide.

A long-acting analog of LH-RH, D-Ala6-desGly10-LH-RH propylamide (D-Ala6-LH-RH PA) was administered intramuscularly in a dose of 250 micrograms to 11 women with amenorrhea in whom the determinations of urinary steroid secretion, progesterone challenge, clomiphene, HMG, and LH-RH tests had been performed previously. Blood samples were taken twice before the injection and at 0.5, 1, 2, 4, 8, 12, 24, 26, 28, 30, and 32 h. No visible side effects were observed. Plasma levels of LH and FSH were determined by radioimmunoassays and expressed in mIU/2nd-IRP HMG/ml. The analog caused a great elevation in plasma LH and FSH levels. The maximal absolute increment for LH was between 3.93 and 115.89 mIU/ml, and the maximal increment in percentage was between 220 and 4,300. The time of the LH peak varied between 0.5 and 12 h. For FSH, the maximal absolute increment was between 6.45 and 50.92 mIU/ml and the maximal increment in percentage was between 63 and 1,442. The peak of FSH occurred in most cases at 4 to 8 h.

Response of plasma aldosterone to orthostatism during follicular and luteal phases of the normal menstrual cycle.

The responses of plasma aldosterone (A) and plasma renin activity (PRA) to orthostatism have been evaluated in 47 women during the follicular and/or luteal phase of the menstrual cycle. Three postmenopausal women and 51 men were also studied for control. Fourteen cycling women and 11 men were studied on a low sodium diet (20 mEq/day) while the rest of the subjects were on normal sodium intake. In addition, 18 women (including those postmenopausal) and 17 men were studied after intravenous administration of 20 mg frusemide. The response of A to orthostatism in women during luteal phase on normal sodium diet with or without frusemide was much greater than in men or women during follicular phase (p less than 0.01) or menopuase (p less than 0.05). However, no differences between groups could be observed in A response while on a low sodium diet. PRA response was similar during follicular of luteal phase fo the cycle as well as in men either on low or normal sodium intake with or without frusemide.

[Effect of administering prostaglandine f2alpha and e2 on lh secretion in rat (author's transl)]. / Efecto de la administración de prostaglandina F2alpha y E2 sobre la secreción de LH en la rata.

Intraperitoneal administration of 100 ng of synthetic LH-RH to castrated male rats, produces a significant elevation of plasma LH values, as determined by RIA. A greater increase is obtained, by administrating 400 ng of LH-RH. Intrayugular injection of physiologic saline reduces basal values of plasma LH. This pattern is not modified by administration of 10 microgram or 100 microgram of PGF2alpha. On the other hand 10 microgram of PGE2 compensates the fall and 100 microgram significantly increases plasma LH over the basal values. Intracarotidly a similar pattern is observed. Plasma LH values decreases in the control group and no modification is observed by the administration of 10 microgram of PGF2alpha. By injecting the same amount of PGE2, plasma LH values remains constant, compensating the fall observed in the controls. Our results show a stimulatory effect of PGE2 and no effect of PGF2alpha on LH secretion in the castrated male rat.

[Radioimmunologic method for the measurement of plasmatic LH in humans (author's transl)]. / Determinación por radioinmunoanálisis de la hormona luteinizante en plasma humano

A simple radioimmunologic method for the measurement of plasmatic LH concentration is described. This procedure utilizes a second antibody for the separation by precipitation of the bound from the free hormone. LH is labelled with 125I by means of a modified Greenwood and Hunter Chloramine T procedure. Three reference compounds, LER-907, MRC 68/40 and 2nd IRP-HMG, have been compared. The daily plasma concentrations of LH along the menstrual cycle in 12 young normal women and the changes induced by 100 mug LHRH were measured, validating the method used since it is capable of detecting the expected variations.

Effects of postovulatory estradiol benzoate administration on women's ovarian function.

The effects of postovulatory estradiol benzoate (EB) administration were studied in six women having normal biphasic, presumably ovulatory, menstrual cycles. EB was administered intramuscularly at dose levels of 0.5 and 10 mg daily for 5 consecutive days. The study covered a total of 30 cycles; parameters studied were basal body temperature, urinary excretion of estrogens and pregnanediol, and characteristics of cervical mucus. EB had no effect on the length of the luteal phase nor on urinary pregnanediol excretion, but a dose of 10 mg/day caused a significant prolongation of the next follicular phase. The elevated estrogen excretion observed at the end of the cycle supports the hypothesis that gestagenic deprivation causes menstrual bleeding.

PIP: The effect of postovulatory administration of estradiol benzoate on the functional life of the corpus luteum was investigated in 6 women. Either .5 or 10 mg of estradiol benzoate was injected im each day for 5 consecutive days beginning on the 1st day of basal body temperature rise. Treatment began on the average on Day 17.5 of the cycle, 1-4 days after the probable day of ovulation. A shortening of the luteal phase was seen with both dosage levels. Prolongation of the follicular phase was noted in the 10 mg/day group but not in the .5 mg group. Some of the administered estradiol benzoate was detectable in the urine; about 20% in the 5 mg doses, about 12% in the 10 mg patients. A rebound phenomenon in pregnanediol excretion was observed after estradiol benzoate treatment. It was concluded that menstrual bleeding is strongly related to a decrease in pregnanediol excretion. It was suggested that this reflects failure of the luteal phase to maintain progesterone secretion but such failure appears independent of the bioavailability of estrogens.

[Radioimmunoanalysis of plasma testosterone]. / Determinación por radioinmunoanálisis de la testosterona plasm

A simple radioimmunoassay procedure for the determination of testosterone concentration in plasma is described. Small amounts of plasma, 0,5 ml for males and 1 ml for females, are extracted with diethyl ether. Recoveries for the extraction are obtained by the addition of labelled tesosterone. The radioimmunoassay is performed directly on the extracts without further purification. Separation of the free from the antibodie bound testosterone is achieved with dextran coated charocoal. Under the used conditions, the calibration curve covers a range between 0,5 and 1,5 ng per sample. Reproducibility is acceptable with a coefficient of variation of 7%. The normal values are slightly higher than those obtained with methods using some purification step of the extract before the assay but due to its simplicity the described method is a suitable one for clinical purposes.