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Pituitary and ovarian response to acute stimulation with LH-RH in normal and anovulatory women.

The LH FSH estradiol and progesterone responses to acute stimulation with LH-RH were studied in 12 normal women with ovulatory cycles (4 in the initial follicular phase, 4 in the mid-follicular phase and 4 in the late follicular phase) and in two castrated women, two under hormonal contraception, two with ovarian amenorrhea, twelve with central amenorrhea of no detectable origin (6 with normal and 6 with low basal gonadotrophins), eleven anovulatory patients with pseudomenstruation, two with anorexia nervosa, and two with pituitary amenorrhea. Each woman received a rapid i.v. injection of 100 microgram synthetic LH-RH at 9:00 a.m. Serum levels of LH, FSH, estradiol and progesterone were determined by radioimmunoassay in samples collected before and 60, 120, 240 and 480 minutes after injection. The findings were : 1) A significant rise in estradiol and progesterone levels, in addition to LH and FSH elevation, in normal women; 2) A lack of ovarian steroid response in the castrated women and in ovarian amenorrheas, which suggests that the source of steroid response to stimulation is not extragonadal; 3) Significant differences in the responses of the four hormones to LH-RH in the women with central amenorrhea in comparison with the normal group with great variability of results; the steroid response in the presence of a positive LH response might correlate with the severity and/or prognosis of the disorder, a point deserving further study; 4) In anovulatory women with pseudomenstruation, LH responses for the most part normal, and particularly, progesterone responses.

Adult↗

Pure crystalline estradiol pellet implantation for contraception.

The subcutaneous implantation of estradiol pellets was found to be a simple and effective contraceptive method with good patient acceptance and minimal untoward effects. The pellets (25 mg each) were implanted through a Kearn's trocar into the abdominal wall, 2.5 to 5 cm above and parallel to Poupart's ligament. The regimen began with four pellets, and the dose was maintained or decreased by one pellet every 6 months (four, three, two, one). A potent progestogen was utilized monthly for induction of withdrawal bleeding. Altogether, 236 patients were followed for a total of 1,060 courses in 6,360 cycles (489,02 woman-years). Two pregnancies occurred during therapy. Pearl's index was 0.37. No significant alterations occurred in body weight and blood pressure. Glucose tolerance test, standard blood profiles, and Papanicolaou smears were normal during therapy. No cases of thrombophlebitis, blurred vision, headaches, gastric symptoms, or amenorrhea-galactorrhea were observed. The suppression of ovulation was confirmed by endometrial biopsies, basal body temperature, and serum follicle-stimulating hormone, luteinizing hormone, estradiol, and progesterone in a selected group of patients.

Abdominal Muscles↗

[Antigonadotropic actions of prolactin. Study of 10 cases of women with hyperprolactinemia].

In order to determine the pituitary or ovarian site of the anti-gonadotrophic action of prolactin (PRL), ten women with hyperprolactinaemia were studied in the following way: 1) Repeated estimations of PRL, gonadotrophins (LH and FSH), plasma estradiol and progesterone during six weeks of treatment with bromocriptine. 2) Verification of the effects of estradiol benzoate on LH and FSH levels before and after normalisation of prolactin. 3) Exploration of the ovarian response to the administration of human menopausal gonadotrophin. Without it being possible to exclude any direct effect of prolactin on the ovary, it may be affirmed that the hormone decreases the sensitivity of the gonadotrophic cells to the positive feedback mechanism exerted by plasma estradiol.

Adult↗

Pituitary responses in LH secretion to LHRH during pregnancy.

Thirty-six pregnant women and 15 normally menstruating women were each given 100 microng of synthetic luteinizing hormone releasing hormone (LHRH) by a single intravenous injection. Human chorionic gonadotropin (hCG), luteinizing hormone (LH), and follicle stimulating hormone (FSH) levels were determined by specific radioimmunoassay (RIA) technics. For the determination of the serum LH levels, the LHbeta-RIA method, which is unaffected by hCG at sample levels as high as 500 IU/ml, was used. Serum concentrations of LH and FSH were lower in pregnant women than in the normal women in the follicular and luteal phases. While the release of LH was observed in pregnant women following the administration of LHRH, the average net increase was less than that seen in both the follicular and luteal phases. During pregnancy, there was a progressive decrease in the LH response to LHRH, but no release of FSH.

Adult↗

[Effect of clomiphene on the restoration of ovulation in androgen-sterile rats].

In the androgen-sterile rats given 10-250 mug of testosterone-propionate there was observed at the early postnatal period a reduction in the LH-RP level in the hypothalamus, of the LH in the hypophysis and the blood, of the weight of the ovaries and of the corporal luteum count in them, as well as an increase in the dopamine level in the anterior portion of the hypothalamus. Klomiphen administration for 5 days in a dose of 20 mug led to the normalization of these indices and to the appearance of ovulation, but failed to restore the capacity to pregnancy. Prolonged klomiphen administration (20 mug every 3 days for a period of 1 month) also failed to restore this capacity.

Animals↗

Inhibition of ovulation in women by chronic treatment with a stimulatory LRH analogue--a new approach to birth control?

A stimulatory luteinizing hormone-releasing hormone (LRH) analogue D-Ser(TBU)6-EA10-LRH was administered subcutaneously once daily in a dose of 5 microgram to four regularly menstruating women. Treatment was instituted within the first three days of the menstrual bleeding and continued for 22--30 days. Ovulation was inhibited in all the women during the treatment cycle. The treatment resulted in disturbances in the pituitary gonadotropin secretion which presumably led to disordered follicular menuration and anovulation. The maximum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) responses to the LRH analogue were obtained during the first few days of treatment. The gonadotropin responses then rapidly decreased during the prolonged treatment. This change in the pituitary responsiveness probably prevented the release of a normal preovulatory LH surge. After the treatment, all the women resumed normal ovulatory menstrual cycles. The results suggest that it might be possible to use stimulatory LRH analogues for birth control.

Adult↗

Luteinizing hormone-releasing hormone and the human menstrual cycle.

Plasma concentrations of LHRH were measured by radioimmunoassay in daily samples obtained from 10 normally ovulating women. The normalcy of each menstrual cycle was determined by measuring luteinizing hormone (LH), follicle-stimulating hormone (FSH), total estrogen, and progesterone concentrations. Six women had consistently measurable immunoreactive LH-releasing hormone (LHRH) in every blood sample. In four, LHRH could not be detected in some of the samples, more frequently during the follicular phase. LHRH levels varied between 10 and 35 pg/ml during the menstrual cycle. At midcycle, coincident with the LH surge, the mean LHRH level (17.6 +/- 4.4 pg/ml) was not significantly different from the mean follicular or luteal phase values. The lowest LHRH level, 11.4 +/- 4.6 pg/ml, was observed on the day of the estrogen surge. A detailed evaluation was made of the specific days of the cycle. Blood samples obtained from an indwelling venous catheter every 20 minutes over a 3 or a 5 hour period during the days of the estrogen surge and the LH surge and on the following day showed no correlation between OHRH, LH, and FSH values.

Antigens↗

An apparently direct inhibitory effect of oestrogen on the human testis.

In men suffering from prostatic cancer, i.v. administration of 12 g diethylstilboestrol diphosphate within 20 days resulted in a decrease of the LH serum level to about 50% (P less than 0.05), whereas the total testosterone level decreased to less than 5% (P less than 0.001) and the apparently free testosterone level to less than 2% of the initial values (P less than 0.001). Hence, the "systemic antiandrogenic effect" of oestrogen can be explained (1) by indirect inhibition of testicular androgen secretion via diminution of hypophyseal gonadotrophin secretion, (2) by direct inhibition of testicular androgen secretion and (3) by elevation of the capacity of testosterone binding beta-globulin.

Aged↗

A syndrome of functional hypogonadotropic hypogonadism and sterility in a male with elevated serum estradiol.

A 36-year-old male complaining of impotence was examined. He was a genotypic male. Phenotypically, he exhibited signs of long-standing estrogen excess, such as feminine body build, gynecomastia, and varicose veins. His testes were soft and borderline small, and his prostate was small and soft. However, he had a normal-sized penis, normal male hair distribution, normal sense of smell, and normal intelligence. The laboratory data were compatible with mild hypogonadotropic hypogonadism. Serum estradiol (E2) levels were consistently elevated. The patient had azoospermia and a decreased semen volume. Inappropriately low levels of luteinizing hormone and follicle-stimulating hormone responded normally to gonadotropin-releasing hormone and clomiphene citrate. Levels of both testosterone (T) and E2 increased dramatically after prolonged clomiphene medication and in response to human chorionic gonadotropin. There was no change in either T or E2 levels in response to manipulations of the pituitary-adrenal axis. It is concluded that the elevated E2 level was responsible for suppression of gonadotropins which, in turn, caused mild hypogonadism and sterility in this patient. According to the stimulation tests, the source of the elevated E2 levels was testicular.

Adolescent↗

Investigations of hormones during early abortion induced by prostaglandin F2alpha and 15(S)-methyl-PGF2alpha.

In early pregnancy up the 7th week of pregnancy PGF2alpha was infused and 15(S)-methyl-PGF2alpha was applied i. m. to induce menstruation in 20 or 19 cases, respectively. In the tested form of application 15(S)-methyl-PGF2alpha is effective in 89 per cent of the cases and in 74 per cent complete abortion was achieved. PGF2alpha produced bleeding in 80 per cent only and complete abortion in 55 per cent. The differences in these two groups were not statistically significant. The steroid hormones estradiol and progesterone decrease in a successful application of PGs for induction of abortion and reach a value of 75 per cent at the onset of bleeding. The LH concentration in plasma becomes smaller too. In some cases there is a temporary increase in hormones shortly after starting treatment. The results could indicate that the considerable decrease in hormones before the onset of bleeding might be caused by an alteration of the corpus luteum, which is effective during early pregnancy.

Abortion, Induced↗

[Plasma concentrations of LH and of sex steroids during the normal menstrual cycle and during contraceptive treatment].

The authors have studied the long-term effects of combined oestrogen-progestogen on the secretion of gonadotrophins and on ovarian function. Estimation of the radio-immune levels of the plasma concentrations of the pituitary luteinizing hormone (LH), of oestradiol (E2), of progesterone (P) and of 20 alpha hydroxyprogesterone (20 alpha OHP) and of testosterone (T) served as a base for this study. A test cycle and 8 cycles in which a combination of 50 micrograms of ethinyl-oestradiol and 0.5 mg of norgestrel were administered were studied in 4 normal volunteer women. A pituitary stimulation test using 50 micrograms of gonadotrophin "releasing factor" (LH-RH) was given during the 7th cycle. Ovarian stimulation using human menopausal gonadotrophins (HMG) was given during the 8th cycle of treatment in 3 of the women and in 3 other subjects. Pituitary secretion of LH and ovarian secretion of E2 and P are partially inhibited. Pituitary response to the injection of LH-RH stays normal but 5 out 6 patients had no response to stimulation by gonadotrophins. These results allow us to conclude that the lowering of production of gonadotrophins during treatment with combination oestrogen and progestagens is responsible for inhibition of ovarian activity, and that there is a delay before the latter respond to stimulation by either endogenous or exogenous gonadotrophins.

Adult↗

The significance of galactorrhea in patients with normal menses, oligomenorrhea, and secondary amenorrhea.

Thyroid-stimulating hormone and prolactin (PRL) were measured in a group of 149 women with galactorrhea. Three of these patients were found to have primary hypothyroidism. In the remaining 146 patients, the PRL assay was correlated with the menstrual history and the results of hypocycloidal polytomography. Sixty-two per cent of these patients had hyperprolactinemia and 35 per cent had abnormal tomograms. Nine patients with abnormal x-rays had normal prolactin levels. None of the patients with normal menses and normal PRL was found to have an abnormal x-ray. Fourteen of the 15 patients with PRL levels greater than 200 ng. per milliliter had abnormal tomograms. Almost 70 per cent of patients with secondary amenorrhea and low estrogen status had abnormal x-rays. In patients with oligomenorrhea and secondary amenorrhea with normal estrogen status, it was not possible to differentiate between patients with normal or abnormal tomograms based on the level of serum PRL. Polytomography remains the single most important diagnostic test in establishing the presence of a pituitary tumor.

Adolescent↗