Pelvic endometriosis: reproductive and menstrual risk factors at different stages in Lombardy, northern Italy.

AIM: To analyse the relationship between reproductive and menstrual factors and different stages of pelvic endometriosis. METHODS: Between 1987 and 1990 a case-control study of risk factors for pelvic endometriosis was conducted. Cases comprised 376 women (median age 32 years) with pelvic endometriosis confirmed by laparoscopy or laparotomy admitted to any one of three clinics in Lombardy, northern Italy. A total of 129 (34.3%) of these women were at stage 1, 76 (20.2%) at stage 2, 96 (25.5%) at stage 3, and 75 (19.9%) at stage 4, according to the American Fertility Society revised classification of endometriosis. Controls comprised 522 women admitted to hospital for acute conditions. RESULTS: The risk of endometriosis decreased with increasing number of births. The estimated odds ratios (OR) were similar in different stages of the disease: for example, compared with nulliparous women, the OR of endometriosis at stage 1 was 0.1 in women who reported two or more births and the corresponding values were respectively 0.1, 0.2, and 0.2 for endometriosis at stages 2, 3, and 4. Cases reported fewer induced abortions than controls: the estimated ORs compared with no induced abortion were 0.4, 0.5, 0.2, and 0.2 in women who reported one or more induced abortions for subsequent stages of endometriosis. Women with irregular menstrual cycles were at less risk of the disease: compared with women who reported lifelong regular cycles the estimated ORs were 0.3, 0.5, 0.5, and 0.3 for disease stages 1-4 respectively. No consistent association emerged between the ages at menarche and at first delivery and the risk of endometriosis. CONCLUSIONS: This analysis provides further evidence that reproductive and menstrual factors are associated with the risk of endometriosis. The observation that early and late stages of the disease share similar epidemiological characteristics suggests an epidemiological (and pathogenetic) continuum between various stages of the disease.

Contraceptive methods and risk of pelvic endometriosis.

The relation between contraceptive methods and risk of pelvic endometriosis has been analyzed in a case-control study. Cases were 376 women with laparoscopically or laparotomically confirmed pelvic endometriosis admitted to a network of Obstetrics and Gynecology Clinics in Lombardy, Northern Italy. Controls were 522 women admitted for acute non-gynecological and non-obstetrics conditions to the same hospitals where cases had been identified. A total 153 women (40.3%) out of the 377 cases and 154 (29.7%) out of the 522 controls reported ever oral contraceptive (OC) use: the corresponding relative risk (RR) was 1.6 (95% confidence interval, CI, 1.2-2.2). The risk was restricted to ex-OC users (RR 1.7, 95% CI 1.3-2.4), the estimated RR for current users being 0.9 (95% CI 0.5-1.9). No clear relation emerged with duration, recency and latency of OC use and risk of endometriosis. In comparison with never IUD users, the risk for ever users was 1.3 (95% CI 0.6-2.8), and no clear relation emerged with duration of use. Likewise, no association was observed between barrier method of contraception and risk of endometriosis (RR ever vs never users 0.5, 95% CI 0.3-1.4). The role of selection and other biases should be considered in the interpretation of epidemiological data on the role of OC on the risk of endometriosis.

PIP: In northern Italy, physicians compared data on 376 women with laparoscopically or laparotomically confirmed pelvic endometriosis with data on 522 age-matched controls admitted for acute nongynecologic and nonobstetric conditions to the same hospitals to examine the association between contraceptive methods and pelvic endometriosis. Cases were more likely to have ever used oral contraceptives (OCs) than controls (40.3% vs. 29.7%; relative risk [RR] = 1.6), but the risk was limited to former OC users (RR = 1.7 vs. 0.9 for current users). There was no clear association with duration, recency and latency of OC use and risk of endometriosis. The relative risk of endometriosis for ever users of the IUD was 1.3. Duration of IUD use was not associated with endometriosis risk. Use of barrier methods was not correlated with risk of endometriosis (RR = 0.5). Before making any conclusions on the association between use of contraceptive methods and pelvic endometriosis, one should consider possible selection and other biases when interpreting epidemiologic data. For example, painful menstruation is a common symptom of endometriosis and a major indication for OC use. Thus, women with endometriosis-induced dysmenorrhea tend to be ever OC users.

Requirement of oestrogens for the sensitivity of prolactin cells to vasoactive intestinal peptide in rats and man.

Vasoactive intestinal peptide (VIP) is a prolactin-releasing hormone which is involved in the multifactorial modulation of prolactin secretion in mammals. Intravenous injection of VIP (1 microgram/kg) to fertile women increased plasma prolactin levels and heart rate and reduced diastolic pressure. The same treatment to menopausal women caused similar cardiovascular effects but did not modify plasma prolactin levels. In contrast, TRH (200 micrograms, i.v.) induced a significant increase in plasma prolactin levels in both fertile and menopausal women. The relevance of oestrogens in affecting VIP-stimulated prolactin secretion was evaluated in vitro by measuring prolactin release from pituitary cells of control and ovariectomized rats. The sensitivity of rat mammotrophs to VIP, but not to TRH, was completely suppressed 3 or 4 weeks after ovariectomy. Furthermore, implantation of rats with a silastic capsule containing oestradiol-17 beta during ovariectomy, preserved the cell responsiveness to VIP. The prolactin-releasing property of VIP was also restored when pituitary cells from ovariectomized rats were cultured for 3 days in the presence of 10 nmol oestradiol-17 beta/l before being used for prolactin release experiments. The present study shows that the ability of prolactin-secreting cells to respond to the stimulatory action of VIP requires high levels of circulating oestrogens, both in man and rats.

Presurgical treatment of uterine fibroids by using gonadotropin-releasing hormone agonists.

Evaluation of clinical intra- and post-operative benefits of pre-myomectomy therapy with a Gonadotropin-Releasing Hormone Agonist (GnRH-A) (Goserelin) in anemic and non-anemic patients suffering from uterine leiomyomas. Evaluation of ultrasound, estradiol (E2) and hematological measurements before and during treatment with a GnRH-a in thirty women with uterine leiomyomas, comparing pre-treated patients operative time, total intraoperative blood loss, blood counts and febrile morbidity with of thirty-five control women. GnRH-A pre-treatment cures, iron-deficiency anemia, significantly reduces myoma and uterine volume (p < 0.01), total intra-operative blood loss (p < 0.001), decreases post-operative febrile morbidity, though it does not reduce operative time. GnRH-A pre-treatment over a period no longer than two months should be suggested in anemic patients suffering from uterine leiomyomas who have to undergo myomectomy.

Conservative surgical treatment in infertile patients with endometriosis.

In the period 1985-1988 23 infertile patients with pelvic endometriosis underwent conservative surgery with microsurgical technique. 8.7% (only 2 women) of the patients were in 2nd stage, 43.5% in 3rd stage and 47.8% in 4th stage of the American Fertility Society classification (1985). Associated pathology was found in 52.2% of the patients. Surgical techniques and results are presented. We obtained 13 (56.5%) full term pregnancies. The postoperative birth rate was 50% in 2nd stage, 80% in 3rd stage and 36.4% in 4th stage. Associated pathology was present in 69.2% of pregnant patients. Ten women (43.5) did not conceive: 10% were at 2nd, 20% at 3rd and 70% at 4th stage. Associated disease was present in 30% of women that did not become pregnant.

Ovarian hyperstimulation syndrome (OHS): a case of severe OHS.

A 26 year old patient, who underwent an ovulation stimulation therapy (Clomiphene /UH-FSH), monitored only by ultrasound presented a severe Ovarian Hyperstimulation Syndrome (OHS). beta-HCG values confirmed conception, that outcame in an abortion. During an ovulation stimulation therapy, patient's management with the ultrasound examination, is often inadequate and it's moreover necessary to determine the 17 beta E2 levels.