Unexplained habitual abortion is associated with a reduced endometrial release of soluble intercellular adhesion molecule-1 in the luteal phase of the cycle.

Although the mechanisms causing recurrent spontaneous abortion (RSA) remain frequently speculative, recent evidence indicates that a specific uterine immune-endocrine network plays a pivotal role in the continuation of pregnancy. We have recently demonstrated that an adhesion molecule of the immune system, named intercellular adhesion molecule (ICAM)-1, is markedly expressed at both protein and mRNA levels in endometrial stromal cells and is able to mediate their interaction with lymphoid cells. Moreover, we have shown that the soluble form of ICAM-1 (sICAM-1) can be released by the endometrium in a hormone-dependent manner. The present study was designed to determine whether surface and/or sICAM-1 expression by cultured endometrial stromal cells could be related to early pregnancy loss in patients with a history of unexplained RSA. Luteal-phase endometrial biopsies were obtained from eight patients who had experienced three or more consecutive unexplained RSAs in the first trimester and 12 control fertile women. Surface ICAM-1 was similarly expressed on luteal-phase endometrial cells obtained from women with and without a history of unexplained RSA. In contrast, the endometrial release of sICAM-1 was significantly lower in abortion-prone patients than in control women. sICAM-1 is a cytokine-inducible molecule able to interfere with several immunological responses and the reduced levels of the protein shed by the endometrium in patients who have suffered from unexplained RSAs may reflect the presence of an altered immunological environment during the early phases of pregnancy.

Gonadotropin-releasing hormone agonist-induced hypoestrogenism and blood flows in cerebral arteries.

OBJECTIVE: To evaluate the effect of the hypoestrogenism induced by GnRH agonist (GNRH-a) therapy on cerebral vessel blood flow. DESIGN: Open, controlled study. SETTING: Tertiary care units of the University of Milan, Italy. PATIENTS: Young women scheduled to undergo 6 months of therapy with a GnRH-a; a control group was also enrolled. INTERVENTIONS: In both groups, the pulsatility index of both the internal carotid artery (ICA) and middle cerebral artery (MCA) was measured by means of Doppler ultrasound over a period of 6 months. MAIN OUTCOME MEASURE: The ICA and MCA pulsatility index. RESULTS: No variation in the pulsatility index of either artery was found in either group. CONCLUSIONS: A 6-month period of GnRH-a-induced hypoestrogenism in young women does not lead to any variation in the blood flow of cerebral vessels. This provides some reassurance as to the safety of these drugs in relation to the role that the reactivity of peripheral arteries may play in determining risk of cardiovascular disease. Furthermore, our results show that blood flow in the cerebral vessels of young subjects is under extraestrogenic control and that this may counterbalance estrogen deprivation through mechanisms that probably are no longer active in the perimenopausal years.

Induction of follicle maturation and ovulation by gonadotropin administration in women with beta-thalassemia.

The objective of this paper was to assess the ability of gonadotropin administration to induce ovarian steroidogenesis, follicle maturation and ovulation in hypogonadal women affected by beta-thalassemia. Thirteen hypogonadal thalassemic women underwent a test with gonadotropin-releasing hormone (GnRH), with estimation of serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels. They were then administered human menopausal gonadotropin (hMG) for a period ranging from 11 to 15 days with a total dose variable from 3,300 to 4,200 IU. In each patient, the initial dosage of 300 IU daily, adopted for the first 9 days, was modified subsequently according to the ovarian morphology, as shown by serial echographic examinations and by serum estradiol levels. In those patients in whom a dominant follicle was evidenced and the occurrence of pregnancy could be excluded, induction of ovulation was attempted by administration of 10,000 IU of human chorionic gonadotropin (hCG). All patients displayed a reduced LH and FSH rise in response to GnRH. Upon hMG administration, they exhibited echographic evidence of follicular growth with a clear-cut increase of serum estradiol, which peaked between the 9th and the 16th day from the start of treatment. In two out of three patients in whom a dominant follicle developed, ovulation was induced successfully by hCG injection, as shown by the increase of serum progesterone and by the ultrasonographic demonstration of a corpus luteum. This study has shown that, by proper pharmacological stimulation, the steroidogenic function of the gonads and even ovulation can be reinstated in hypogonadal thalassemic women.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma FSH, LH and prolactin levels in postmenopausal women undergoing cyclofenil treatment.

Ten postmenopausal women were studied in an attempt to identify the mechanism of action of cyclofenil, a non-steroidal anti-estrogen which has proved to be effective in the climacteric syndrome. A double-blind inter-patient clinical investigation was undertaken, with patients assigned randomly to treatment for 10 days with cyclofenil, 400 mg/day, or else conjugated estrogens, 1.25 mg/day, always given orally at 8 a.m. Serum FSH, LH and PRL levels were determined daily 2 days before, during and for 2 days after treatment. On the first and tenth day of treatment, five blood samples were drawn between 8 a.m. and 4 p.m. to ascertain if there was any drug-induced variation in the hormonal secretory patterns. Furthermore, endometrial biopsies of all patients were taken before and immediately after the 10-day treatment. In 5 patients, endometrial biopsies were repeated after 3-6 months of therapy with cyclofenil. The results indicate that cyclofenil has two opposing actions on the hypothalamic-hypophyseal axis, one estrogen-like, in that it depresses serum FSH levels, and the other antiestrogen-like, in that it depresses serum PRL levels. They also show that at both the peripheral and the central level cyclofenil is a drug of first choice for postmenopausal women at risk for endometrial and mammary neoplastic pathology.

Bromocriptine induced pregnancy in two cases of euprolactinemic hypothalamic amenorrhea.

Two euprolactinemic women with hypothalamic amenorrhea, previously unsuccessfully submitted to clomiphene citrate therapy, were treated with bromocriptine. PRL secretion was studied in basal conditions and under dynamic tests: TRH and chlorpromazine. Serum FSH, LH and 17-beta-estradiol were determined before and during the treatment. Both patients conceived, and one delivered a healthy baby at term. Bromocriptine appears to be an effective drug for treating women with hypothalamic amenorrhea, particularly those unresponsive to clomiphene.

[Current significance of the endocrine monitoring in the treatment of amenorrhea]. / Significato attuale del monitoraggio endocrino nel trattamento della amenorrea

PIP: The use and limitations of various endocrine monitoring tests in the diagnosis and treatment of amenorrhea are discussed. 100 cases of amenorrhea were studied by measuring serum gonadotropins, estradiol, and prolactin levels under basal conditions and after administration of luteinizing hormone-releasing hormone, ethinyl estradiol, and clomiphene citrate. The ethinyl estradiol test was found to be particularly significant in determining the response of the hypothalamus-pituitary gland system to the gonadal signal. The patients who showed positive or negative responses to the ethinyl estradiol test showed similar responses to clomiphene, which appears to indicate that the latter has a similar estrogenlike action; it is concluded that the estrogen test may have prognostic value for the purpose of clomiphene treatment. Although the tests described are useful, much further research is necessary to determine the neuropsychic control mechanism which governs the development of the menstrual cycle, and it is often very difficult or impossible to reach a correct diagnosis of the causes of amenorrhea, which is a very aspecific symptom.^ieng