High levels of women's satisfaction and compliance with transdermal contraception: results from a European multinational, 6-month study.

OBJECTIVE: To investigate compliance, satisfaction, and preference in women using a transdermal contraceptive patch. METHODS: Women (18-46 years) from eight European countries used contraceptive patches (norelgestromin 6 mg, ethinylestradiol 600 µg) for six, 4-week treatment cycles. Compliance, satisfaction, and preference were assessed after 3 and 6 cycles and study completion using self-report methods. RESULTS: Of the 778 participants, 36.8% (n = 287) used no contraception at baseline. The most common methods were oral contraceptives (67.9%, n = 334) and barrier methods (21.5%, n = 106). Of oral contraception users, 63.5% (n = 212) were satisfied or very satisfied with their previous method, but compliance was poor with 77.8% (n = 260) reporting missed doses. After 3 and 6 cycles, >80% of all included women were satisfied or very satisfied with the patch. At study completion, most participants (73.7%) reported a preference for the patch compared to their previous method. Of 4107 cycles, 3718 (90.5%) were completed with perfect compliance. Two pregnancies occurred during this study, representing a Pearl Index of 0.63. No new safety issues were identified and the patch was well tolerated. CONCLUSION: Women were highly satisfied with transdermal contraception and preferred this form of family planning over their previous method. Transdermal contraception represents a valuable addition to contraceptive options with potential to offer high compliance and efficacy.

[The contraceptive method that changed the world]. / La contraccezione ha cambiato il mondo.

During the past century human life expectancy doubled while the birth rate dropped. The widespread use of effective contraceptives has led to a better control of human fertility and changed the structure of modern societies: the elderly now increasingly outnumber the young. Scientifically controlled human reproduction has also resulted in fewer voluntary abortions. The choice of contraceptive strategies differs by geographic area and seems to be linked to such simple mechanisms as the ''door-to-door'' effect. In European countries where the pill is the most widely used contraceptive, interesting variations in the biological profile of oral contraceptive users can be observed; for example, women taking a hormonal contraceptive have only half the risk of developing ovarian cancer. The world is no longer the same since the advent of the pill.

Age, menopausal status and homocysteine levels in women around menopause.

OBJECTIVE: To obtain data on the relation between age, menopause and homocysteine levels in women around menopause, we collected data for a sample of about 500 women attending a menopause clinic in Milan, Italy. STUDY DESIGN: Eligible for the study were all women aged 45-75 years, never HRT users consecutively observed for the first time at the Menopause Center of the 1st Obstetric Gynecological Clinic of the University of Milan. Fasting blood samples for total homocysteine plasma levels were collected during the visit. Of the 490 study subjects, 107 were pre-menopausal and 383 post-menopausal. RESULTS: In the total series, the mean homocysteine level was 8.3 micromol/L (S.D. 3.7, range 3.2-48.8). The values increased from 7.8 micromol/L in women aged <47 years to 9.0 micromol/L in those aged >59. Among pre-menopausal women the mean homocysteine level was 7.7 micromol/L compared to 8.3 micromol/L in post-menopausal women: this difference disappeared on the adjusted values. In post-menopausal women only, no clear relationship emerged between years since menopause and homocysteine levels. CONCLUSION: In our population, age, and not menopausal status, was the main determinant of homocysteine levels in women around menopause.

Looking to Europe: something's changed in Italy.

The new Italian law regulating the use of assisted reproduction technologies (ARTs) prohibits treatment widely practiced in Europe. The new regulations have already given rise to a humiliating form of "reproductive tourism" of Italian subfertile couples.

Effect of three serotonin antagonists on plasma prolactin response to suckling in puerperal women.

The effect of the acute administration of three serotonin antagonists on plasma PRL levels and on the PRL response to suckling was investigated in a group of puerperal women. A single oral dose of metergoline or methysergide induced a significant decrease of plasma PRL levels and abolished the PRL response to suckling. Cyproheptadine administration did not modify either the plasma PRL levels or the PRL response to suckling. These results are discussed in light of the known pharmacological properties of the three antiserotonergic drugs.

Failure of dopamine infusion to suppress the plasma prolactin response to sulpiride in normal and hyperprolactinemic subjects.

In eleven normal women dopamine infusion (5 microgram/Kg/min) significantly lowered plasma prolactin levels but failed to suppress the PRL response to sulpiride (10 or 100 mg i.v.), while the same dose of dopamine was effective in abolishing the PRL response to TRH (200 microgram i.v.). In four hyperprolactinemic women showing an impaired PRL response to sulpiride, dopamine infusion was effective both in lowering PRL circulating levels and in restoring an evident response to sulpiride. This finding suggests an impairment of endogenous dopamine activity in hyperprolactinemic amenorrhea.

Functional characterization of hypothalamic hyperprolactinemia.

PRL secretory dynamics were evaluated by several stimulation and suppression tests in nine patients with hyperprolactinemia due to organic hypothalamic disease. Basal PRL levels ranged between 20-63 ng/ml. There was a normal PRL response to TRH in eight cases (i.e. doubling of basal levels), whereas none of the seven tested subjects responded to sulpiride. The same dissociation of responses was not observed in any of the patients who were still hyperprolactinemic after surgery. Concomitant dopamine infusion resulted in sulpiride-induced PRL release in the four subjects so studied. None of 50 other hyperprolactinemic patients (11 with macroprolactinoma, 18 with microprolactinoma, and 21 with idiopathic hyperprolactinemia) showed PRL response to TRH but not to sulpiride. The TRH-induced PRL increase was significantly higher than that induced by sulpiride in hypothalamic hyperprolactinemia and significantly lower in idiopathic disease as well as in healthy controls; no differences were found in prolactinoma patients. The administration of substances resulting in stimulation of pituitary dopamine receptors, such as dopamine and L-dopa, induced a normal PRL suppression in 7 patients with hypothalamic disease so tested, whereas central nervous system-acting dopaminergic drugs, such as carbidopa plus L-dopa and nomifensine, failed to lower PRL levels in most cases (even when normoprolactinemic after surgery). These data suggest that the mild to moderate hyperprolactinemia found in many patients with hypothalamic lesions is due to dopamine deficiency at the pituitary level, that TRH and dopamine receptors at the lactotropes are intact in this condition, and that paired TRH and sulpiride tests may be of some diagnostic utility in hyperprolactinemic patients. They further suggest that subjects with so-called idiopathic hyperprolactinemia do not suffer from the type of hypothalamic derangement exhibited by patients with organic lesions of the hypothalamus.

Failure of nomifensine administration to discriminate between tumorous and nontumorous hyperprolactinemia.

It has recently been claimed that the PRL-lowering response to nomifensine administration (200 mg, orally) reliably discriminates patients with PRL-secreting tumors from those with so-called functional hyperprolactinemia. In the present study, this test was performed in 15 healthy controls, 7 hyperprolactinemic subjects without evidence of pituitary tumor, and 16 patients with prolactinoma. A decrease of serum PRL to below 65% of basal levels, which seemed to be the cut-off point in the previous study, was obtained in 11 subjects of the first group, in 4 subjects of the second group, and in 4 subjects of the third group. The decrease of mean serum PRL concentration after nomifensine was only significant in the first and second groups. Analysis of variance showed a significant difference in the PRL inhibition by nomifensine between the tumor group and the two groups without evidence of pituitary adenoma. Nevertheless, this study shows that the nomifensine test is unable to discriminate in the individual patient the tumorous or nontumorous origin of excessive PRL secretion.

Cabergoline: long-acting oral treatment of hyperprolactinemic disorders.

Cabergoline, a new orally active dopaminergic drug with an extremely long-lasting PRL-lowering effect, was given to 48 hyperprolactinemic women for 3-18 months (median, 8 months) at doses varying between 0.2-3 mg/week administered one to three times weekly. Serum PRL levels declined to normal in 41 women, 30 of whom received 0.2-1 mg cabergoline once weekly, 8 received 0.2-0.5 mg twice weekly, and 3 received 0.4-0.6 mg 3 times weekly. Five women had slightly supranormal serum PRL levels while receiving 0.3-0.6 mg once weekly, but the dose was not increased because the lower dose had produced the desired clinical benefit. Two women had 50% reductions in their serum PRL levels, but remained hyperprolactinemic while receiving 2-3 mg cabergoline weekly. Among 30 amenorrheic women, 28 had resumption of menses, the exceptions being 2 hypopituitary women, presumptive evidence of ovulation was available in 21. Marked tumor shrinkage occurred after 3-month treatment in 5 of the 6 women who had macroprolactinomas. Only 4 women had side-effects during the first weeks of treatment, and these vanished despite continued cabergoline administration at the same or reduced, but still effective, doses. In a short term, double blind study, cabergoline at 3 different schedules (0.4 mg twice weekly, 0.2 mg 4 times weekly, and 0.4 mg 3 times weekly for 3 weeks, followed by 0.4 mg twice weekly) or placebo was given to a total of 24 hyperprolactinemic women (6 in each subgroup) for 8 weeks, with weekly evaluation of serum PRL levels and side-effects. All 3 cabergoline schedules, but not placebo, induced significant reductions in serum PRL concentrations during the 8-week treatment period. Mild transient side-effects occurred in 7 drug-treated patients (nausea in 5; dizziness in 3). We conclude that cabergoline is effective treatment for hyperprolactinemia. Its efficacy, tolerability, and long duration of action may make it the drug of choice for patients with hyperprolactinemia.

Prolactin-lowering effect of acute and once weekly repetitive oral administration of cabergoline at two dose levels in hyperprolactinemic patients.

To further evaluate the potency and time course of the PRL-lowering effect of single oral doses of cabergoline, two doses of the drug were given to 51 hyperprolactinemic patients who also received 2.5 mg bromocriptine according to a randomized cross-over design. One group (n = 26) received 0.3 mg, and the other (n = 25) received 0.6 mg. Both cabergoline doses induced a significant fall in serum PRL levels, which lasted, on the average, from 3 h to 5 days after 0.3 mg and from 3 h to 14 days after 0.6 mg; the mean maximum decrease after 0.3 mg was -65 +/-4% (+/- SEM), significantly (P less than 0.05) less than that after bromocriptine (group mean, -73 +/- 4%), and it was -76 +/- 3% after 0.6 mg, not significantly different from that induced by bromocriptine (group mean, -71 +/- 4%). The effect of 0.6 mg cabergoline was significantly greater than that of 0.3 mg (P less than 0.01). In a second study designed to evaluate the possible therapeutic use of the new drug, 0.3 or 0.6 mg cabergoline was administered orally once weekly for 9 weeks to 2 groups of 15 and 16 hyperprolactinemic patients, respectively. Serum PRL levels fell significantly by the first week and reached a plateau after 2 doses in the 0.6 mg cabergoline-treated group and after 5 doses in the 0.3 mg-treated group; the absolute PRL decrease was greater in the former. Ten patients in each group achieved normal serum PRL levels, and a marked decrease (greater than 50% of pretreatment values) occurred in all patients treated with 0.6 mg and in 13 treated with 0.3 mg weekly. Resumption of menses occurred during the treatment period in 15 of the 17 premenopausal women with amenorrhea. Six patients who had poor responses had better responses when given higher drug doses for 4 weeks, and serum PRL levels became normal in the 3 receiving 0.6 mg twice weekly. These data confirm that cabergoline is a long-acting oral dopaminergic drug and suggest that it may be a useful agent for the treatment of patients with hyperprolactinemia.

A practical guide to the diagnosis and management of amenorrhoea.

For women of reproductive age, pregnancy and lactation are the two most common physiological causes of amenorrhoea. This article concentrates on pathological causes of amenorrhoea. Primary amenorrhoea refers to the absence of menarche at the age of 16 and secondary amenorrhoea is the cessation of menses for at least 6 months in already cycling women. Amenorrhoea is not a diagnosis but a symptom indicating anatomical, genetic and neuroendocrine abnormalities. It can be determined by two different groups of causes: (a) anatomical defects of the genital organs; (b) endocrine dysfunctions. Both congenital and acquired anomalies in the structure of the uterus and vagina could produce amenorrhoea; nevertheless, in the vast majority of patients, amenorrhoea is related to an ovarian malfunction. Diagnostic work-up includes history, physical examination, laboratory data and imaging. Amenorrhoea resulting from ovarian malfunction is associated with 4 distinct endocrine conditions. Hyperprolactinaemic amenorrhoea is often associated with a pituitary adenoma. Prolactin-lowering drugs, cyclical progestogen and hormone replacement therapy (HRT) are the different choices of treatment for cycle disturbance; a contraceptive pill can be used to ensure contraception, while prolactin-lowering drugs induce fertility in patients who desire pregnancy. Hypogonadotrophic amenorrhoea is frequently associated with stress and nutritional deficiency. If this is the case the patient should simply be counselled. A sequential use of estrogen and progestogen can be suggested to prevent estrogen deficiency or for psychological reasons. If contraception is needed, oral contraception may be the choice for both cycle and fertility control. If the patient desires pregnancy, ovulation may be induced with pulsatile gonadotrophin-releasing hormone (GnRH) in patients with hypothalamic disfunction and with gonadotrophins in patients with pituitary failure. Hypergonadotrophic amenorrhoea is the result of an ovarian failure. There is no curative therapy for these amenorrhoeas. However, a long term hypoestrogenic condition should be treated with estrogen to cure symptoms and to prevent an increased risk of cardiovascular disease and osteoporosis. Normogonadotrophic amenorrhoea is caused by some disturbance in the pattern of pulsatile GnRH secretion. Since these women have some ovarian activity, they are not hypoestrogenic and will bleed in response to progestogen withdrawal. Most of these patients are likely to have polycystic ovarian disease (PCO). Menstrual bleeding can be induced in these women by cyclical progestogen administration or the sequential use of estrogen plus progestogen. Oral contraception is indicated not only in patients who desire to be protected against pregnancy but also in women with acne and hirsutism. These frequently present signs of hyperandrogenism are consistently improved by the ovarian suppression induced by the contraceptive pill. The beneficial effect of the pill can be reinforced by the simultaneous use of antiandrogens. Women with normogonadotrophic amenorrhoea and desiring pregnancy have a less favourable response to all forms of ovulation induction (antiestrogen, GnRH and gonadotrophin preparations.

PIP: Amenorrhea, characterized by anatomical, genetic, and neuroendocrine abnormalities, occurs frequently in adolescents and in 10-20% of women presenting with subfertility. It can be caused by anatomical defects of the genital organs or endocrine dysfunctions. A correct diagnosis, reached through history, physical examination, laboratory data, and imaging, is essential to proper treatment. Amenorrhea resulting from ovarian malfunction, the most common presentation, is associated with four distinct endocrine conditions. Hyperprolactinemic amenorrhea, often linked to a pituitary adenoma, is treated with prolactin-lowering drugs or cyclical progestogen and hormone replacement therapy. Hypogonadotrophic amenorrhea, frequently associated with stress and nutritional deficiency, is generally addressed through counseling and sequential use of estrogen and progestogen. Hypergonadotrophic amenorrhea, the result of ovarian failure, has no curative therapy; however, long-term hypoestrogenicity should be treated with estrogen to prevent an increased risk of osteoporosis and cardiovascular disease and cure symptoms. Finally, in normogonadotrophic amenorrhea, caused by a disturbance in the pattern of pulsatile gonadotropin-releasing hormone, menstrual bleeding can be induced by cyclical progestogen administration or the sequential use of estrogen plus progestogen.

Premature ovarian failure.

Secondary amenorrhoea with elevated gonadotrophins occurring under the age of 40 (premature ovarian failure (POF)), and at the age between 41 and 44 years (early menopause (EM)), respectively, affects 1-2% and 5% of women in the general population. Objective of this study was to evaluate the prevalence of familial cases of POF and EM and to assess the clinical and genetic characteristics of these patients. One hundred and sixty women with idiopathic secondary amenorrhoea before the age of 45 and serum follicle-stimulating hormone (FSH) levels greater than or equal to 40 IU/l were included in the study. Tests performed on patients included complete medical history, pedigree's analysis, clinical pelvic examination, gonadotrophins and thyroid assessment, chromosomal analysis. The 160 patients included in the study showed idiopathic POF (n=130) or EM (n=30). Following pedigree assessment, we were able to identify an incidence of familial cases of 28.5% in the POF group (n=37) and of 50% in the EM group (n=15). POF and EM condition were often present in the same family. There were no differences between POF and EM patients and between familial and sporadic cases regarding age at menarche, personal history, gynaecological history, weight, height and diet habits. There was a statistically significant difference between sporadic and familial cases in age at POF onset: 32.0+/-7.3 years (12-40) compared to 35. 0+/-5.8 (18-40), respectively (P<0.05). The POF and EM families identified showed two or more affected females and transmission through either maternal or paternal relatives; in four families both maternal and paternal transmission was observed. This study suggests that idiopathic POF and EM conditions, differing only in age of menopause onset, may represent a variable expression of the same genetic disease. The different age of menopause onset in these patients may be explained by genetic heterogeneity and/or by different environmental factors. Our results indicate a high rate of familial transmission of the condition. Pedigree's analysis suggests an autosomal or an X-linked dominant sex-limited pattern of inheritance for POF and EM.

Inhibition of prolactin release by serotonin antagonists in hyperprolactinemic subjects.

Metergoline (4 mg) and methysergide (3 mg), two serotonin antagonists known to inhibit prolactin secretion in normal subjects, and the dopaminergic agonist, bromocriptine (2.5 mg) were orally administered in hyperprolactinemic patients. Mean serum prolactin concentration was significantly decreased between 120 and 240 min following the ingestion of all three drugs in comparison with a placebo; a consistent reduction to below 50% of basal values occurred in 10 of 14 patients after metergoline, in 5 of 10 after methysergide, and in 11 of 14 after bromocriptine administration. These data indicate that serotonin antagonists may acutely lower serum prolactin levels in hyperprolactinemic patients similarly to bromocriptine, though their mechanism of action is most likely different.

Hormonal profiles in anovulatory patients treated with gonadotropins and synthetic luteinizing hormone releasing hormone.

Ten patients with hypothalamic anovulation weretreated with a "retard" preparation of synthetic luteinizing hormone releasing hormone (LHRH) after an HMG stimulation in order to induce ovulation and pregnancy. Four of the patient ovulated after intramuscular administration of the LHRH preparation. This study suggests that is is possible to induce ovulation with LHRH in patients pretreated with HMG, and that LHRH has advantages over HCG since it does not induce hyperstimulation even in the presence of exagerated follicular growth. Nevertheless, the optimal conditions for the use and monitoring of LHRH treatment have yet to be clarified.

Spontaneous remission of Cushing syndrome after termination of pregnancy.

A 27-year-old women developed Cushing syndrome during pregnancy. The course of pregnancy was characterized by abnormally low urine and plasma estrogen levels despite the presence of a living fetus. The signs and symptoms of Cushing syndrome disappeared spontaneously within 2 months after delivery. Hormonal studies, however, suggested the presence of an adrenal tumor. An adrenocortical adenoma was found at surgery and removed.

Spontaneous and induced pregnancies in hyperprolactinemic women.

Sixty-nine pregnancies were observed in 57 hyperprolactinemic women (5 with pituitary macroadenoma, 20 with microadenoma, and 32 with normal tomography of the sella turcica). Ten of these pregnancies took place spontaneously in women with mild to moderate hyperprolactinemia (up to 70 ng/ml); 2 were induced by exogenous gonadotropins, 2 by clomiphene, 42 by bromocriptine, and 9 by metergoline; and 4 occurred after pituitary selective adenomectomy. The observed complications included spontaneous abortion (10 cases); headache (7 cases); sellar enlargement (5 cases); and bitemporal hemianopsia (1 subject with macroadenoma). Among 24 women in whom prolactin levels were reevaluated at least 1 month after parturition and/or lactation, 8 showed a decrease in prolactin concentration (less than 50% of pregestational levels), with actual prolactin normalization in 3 and resumption of cyclic menses in 2 previously amenorrheic women. In contrast, no changes in prolactin levels occurred after pregnancies that ended in abortion. These data suggest the following: 1) conception is not uncommon in women with moderate hyperprolactinemia; and 2) pregnancy may be safely induced without prior surgery and/or radiotherapy in hyperprolactinemic women, except those with large pituitary adenomas, and a considerable number of these patients even show a clinical and biochemical improvement after pregnancy.

Maternal and fetal platelet activation in normal pregnancy.

OBJECTIVE: To study the platelet activation phase in normal pregnant women and their fetuses, both in vivo under basal conditions and in vitro after stimulation by adenosine diphosphate (ADP), a weak agonist, and U46619, a strong one. METHODS: Platelet function was investigated in 39 normal pregnant women and their fetuses undergoing fetal blood sampling at 18-37 weeks' gestation, using flow cytometry and the anti-GMP140 monoclonal antibody. This combined technique allows platelets to be investigated in small aliquots of whole blood, and it detects platelet secretion regardless of aggregation. In all cases, the percentage of activated platelets was determined under basal conditions and after addition of platelet agonists: ADP at concentrations of 10 and 50 mumol/L, and U46619, a stable analogue of thromboxane A2, at 1 mumol/L. RESULTS: Compared to nonpregnant controls, pregnant women had a significantly lower percentage of activated platelets after addition of U46619 (P = .02). Compared to their mothers, fetuses had significantly inferior platelet activation after addition of both platelet-activating factors at all concentrations used (ADP 10 mumol/L, P < .0001 and ADP 50 mumol/L, P < .0001; U46619, P < .0001). Maternal and fetal platelet activation did not change with duration of gestation. In the fetus, the percentage of activated platelets did not correlate with hematocrit, pH, or oxygen pressure, but it correlated significantly with platelet count after addition of U46619 (r = 0.45, P = .006). CONCLUSIONS: Decreased platelet activation in both pregnant women and fetuses suggests the action of a plasma factor that selectively inhibits prostaglandin-dependent activation. Prostacyclin, which is known to decrease platelet aggregation and release reactions caused by agonists, might have a greater inhibitory effect in the fetus than in the mother, or be present in larger amounts in the fetus.

Randomized comparison of vaporizing electrode and cutting loop for endometrial ablation.

OBJECTIVE: To compare endometrial ablation using a vaporizing electrode with resection using a standard cutting loop, evaluating distension fluid absorption, operating time, and ease of procedure. METHODS: Premenopausal menorrhagic women with normal hysteroscopic and endometrial biopsy findings were allocated randomly to endometrial vaporization (n = 47) or resection (n = 44). Distension medium deficit, operating time, and degree of difficulty of the procedure were determined at surgery. Menstrual pattern of women in both groups was also assessed after 1-year follow-up. RESULTS: Mean +/- standard deviation (SD) distension fluid deficit was 109+/-126 mL in the vaporization and 367+/-257 mL in the resection group (mean difference 258 mL; 95% confidence interval 175, 341 mL; P < .001, unpaired t test). Mean +/- SD operating time was, respectively, 9.2+/-3.1 minutes versus 10.7+/-2.5 minutes. The surgeon classified intraoperative difficulties as none in 32, minimal in 11, moderate in four, and severe in none in the vaporization group, and 17, 14, seven, and six in the resection group. Menstrual pattern at 1 year in the former group was amenorrhea in 17 (36%) cases, hypomenorrhea or spotting in 20 (43%), normal flows in 10 (21%), and menorrhagia in none compared with, respectively, 21 (48%), 14 (32%), seven (16%), and two (5%) in the latter group. CONCLUSION: Endometrial ablation with the vaporizing electrode limited fluid absorption compared with resection by the standard cutting loop. Long-term effects on uterine bleeding were similar.

Hysteroscopic myomectomy: long-term effects on menstrual pattern and fertility.

OBJECTIVE: To determine the effects of hysteroscopic myomectomy on menorrhagia and infertility and the influence of intramural extension on surgical feasibility and long-term outcomes. METHODS: We studied 108 women who had first-line hysteroscopic resection of submucous pedunculated (n = 54), sessile (n = 30), or intramural (n = 24) leiomyomas over 7 years at an academic department specializing in endoscopic surgery. RESULTS: The mean (+/- standard deviation) operating time and distension medium deficit were 18+/-7 minutes and 204+/-276 mL in the pedunculated lesion group, 23+/-9 minutes and 278+/-269 mL in the sessile lesion group, and 32+/-8 minutes and 335+/-272 mL in the intramural lesion group, respectively. More than one procedure was required to complete myoma removal in 14 (26%) of 54, eight (26%) of 30, and 12 (50%) of 24 subjects in the pedunculated, sessile, and intramural lesion groups, respectively. After a mean follow-up of 41 months, myomas recurred in 27 subjects, with a 3-year cumulative rate of 34%. Twenty women had recurrent menorrhagia, with a 3-year cumulative probability of 30%. The 3-year cumulative probability of conception was 49% in women with pedunculated lesions, 36% in those with sessile lesions, and 33% in those with intramural lesions. The study had 80% power to detect five- and three-fold increases in menorrhagia recurrence and conception rates, respectively, in the mainly intramural myoma group compared with the completely or mainly intracavitary myoma group. CONCLUSION: Hysteroscopic resection of submucous myomas gives satisfactory menorrhagia control and limited recurrence, but the benefit for infertility was less impressive. Myoma intramural extension did not have a substantial influence on any of the long-term outcomes but affected operating time and the number of procedures needed for complete removal.

Determinants of high-grade dysplasia among women with mild dyskaryosis on cervical smear.

OBJECTIVE: To identify the epidemiologic characteristics of women who have mild dyskaryosis on cervical smear but cervical intraepithelial neoplasia (CIN) grade II or III at biopsy. METHODS: We analyzed information from 291 women (median age 33 years, range 17-69) observed for the first time with a single smear test showing mild dyskaryosis. All subjects underwent colposcopy, and histologic confirmation was obtained by biopsy. We compared the characteristics of women who had CIN I or no evidence of CIN with those of women with CIN II or III at biopsy. RESULTS: Twenty-eight women (10%) had CIN I at biopsy, 46 (15%) CIN II, and 23 (8%) CIN III. The frequency of CIN II or III tended to decrease with increasing education; compared with women reporting 11 or fewer years of education, the multivariate odds ratios (OR) of CIN II or III lesions was 0.5 (95% confidence interval [CI] 0.3-0.9) in those reporting 11 years of education or more. Compared with nulliparas, the OR of CIN II or III was 1.8 (95% CI 1.1-3.5) for parous women. Furthermore, compared with never-smokers, the OR of CIN II or III was 2.3 (95% CI 1.0-5.4) for current smokers. Ex-smokers were at increased risk, too; the estimated multivariate OR was 3.8 (95% CI 1.9-7.6). Compared with women reporting one sexual partner, the multivariate ORs of CIN II or III were 1.4 and 2.3 for women reporting two to three or four or more sexual partners, respectively (chi 2(1) trend = 6.65, P < .05). CONCLUSION: Our results show that smoking is a risk indicator of CIN II or III in women with a single smear showing mild dyskaryosis. Parous women, those of low social standing, and those reporting multiple sexual partners also are at increased risk of CIN II or III.