1 and 2 mg 17beta-estradiol combined with sequential dydrogesterone have similar effects on the serum lipid profile of postmenopausal women.

OBJECTIVES: The aim of this study was to assess the effects of 1 and 2 mg 17beta-estradiol on serum lipid profile. Beneficial effects have been clearly established in previous studies with a 2 mg dose; further evidence was required to confirm the beneficial effects of a 1 mg dose. METHODS: This double-blind, placebo-controlled study involved 579 postmenopausal women randomized to oral treatment with placebo, 1 mg/day 17beta-estradiol sequentially combined with 5 or 10 mg/day dydrogesterone for the last 14 days of each 28-day cycle, or 2 mg/day 17beta-estradiol sequentially combined with 10 or 20 mg/day dydrogesterone for the last 14 days of each 28-day cycle. Treatment was continued for 26 cycles. RESULTS: High density lipoprotein (HDL) cholesterol levels were significantly (p<0.05) increased after 26 cycles in all active treatment groups compared with placebo. In addition, low density lipoprotein (LDL) cholesterol and lipoprotein(a) levels were significantly reduced, and apolipoprotein A1 and triglyceride levels were significantly increased, in all active treatment groups after 13 and 26 cycles. CONCLUSIONS: The results of this study clearly indicate that sequential combinations of either 1 or 2 mg 17beta-estradiol with dydrogesterone are associated with long-term, favorable changes in the serum lipid profile. There was no evidence that dydrogesterone compromised the 17beta-estradiol-induced improvements in lipid profile.

Endometrial safety and bleeding patterns during a 2-year study of 1 or 2 mg 17 beta-estradiol combined with sequential 5-20 mg dydrogesterone.

OBJECTIVE: To assess the endometrial safety and bleeding patterns of 17 beta-estradiol sequentially combined with dydrogesterone. METHODS: Endometrial safety and bleeding patterns were assessed in 579 postmenopausal women randomized to oral treatment with placebo, 1 mg/day 17 beta-estradiol sequentially combined with 5 or 10 mg/day dydrogesterone for the last 14 days of each 28-day cycle, or 2 mg/day 17 beta-estradiol sequentially combined with 10 or 20 mg/day dydrogesterone for the last 14 days of each 28-day cycle. Treatment was continued for 26 cycles. Proliferative endometrium, endometrial hyperplasia and endometrial malignancy in the end-of-study biopsy were considered as inadequate progestational responses. RESULTS: Biopsies were not available in 137 women mainly because of an insufficient treatment period or non-compliance. An adequate progestational response was seen in more than 98% of the 442 women who underwent biopsy after treatment. Bleeding data were not available in 193 women, most of whom did not remain on treatment for the full 26 cycles. The 1-mg 17 beta-estradiol dose was associated with less cyclic and intermittent bleeding than the 2-mg dose. Higher doses of dydrogesterone were associated with a higher incidence of cyclic bleeds and a later day of onset, while duration, severity and regularity were similar in all groups irrespective of estradiol or dydrogesterone dose. CONCLUSION: Sequential combinations of 1 mg 17 beta-estradiol with 5 or 10 mg dydrogesterone and 2 mg 17 beta-estradiol with 10 or 20 mg dydrogesterone are associated with very good endometrial safety. The incidence of bleeding is lower with the 1-mg dose of 17 beta-estradiol.

Female sterilization: an update.

Female sterilization is the most popular form of birth control in the world. It is performed laparoscopically or through a minilap, depending on the timing (postpartum) and where the patient lives. It is a safe and efficacious procedure with few complications that can be performed under local or general anaesthesia. The techniques presently in use are all adequate and the choice should evolve from a discussion between the doctor and the patient.

17beta-estradiol vaginal tablet versus conjugated equine estrogen vaginal cream to relieve menopausal atrophic vaginitis.

OBJECTIVES: The efficacy and safety of 25-microg 17beta-estradiol vaginal tablets (Vagifem) were assessed and compared with 1.25-mg conjugated equine estrogen vaginal cream (Premarin Vaginal Cream) for the relief of menopausal-derived atrophic vaginitis, resulting from estrogen deficiency. DESIGN: In a multicenter, open-label, randomized, parallel-group study, 159 menopausal women were treated for 24 weeks with either vaginal tablets or vaginal cream. Efficacy was evaluated by relief of vaginal symptoms and concentrations of serum estradiol and follicle-stimulating hormone. Safety was monitored by the incidence of adverse events, evaluation of endometrial biopsies, and clinical laboratory results. Patients also assessed the acceptability of the study medications. RESULTS: Composite scores of vaginal symptoms (dryness, soreness, and irritation) demonstrated that both treatments provided equivalent relief of the symptoms of atrophic vaginitis. At weeks 2, 12, and 24, increases in serum estradiol concentrations and suppression of follicle-stimulating hormone were observed in significantly more patients who were using the vaginal cream than in those who were using the vaginal tablets (p < 0.001). Fewer patients who were using the vaginal tablets experienced endometrial proliferation or hyperplasia compared with patients who were using the vaginal cream. Significantly more patients who were using the vaginal tablets rated their medication favorably than did patients who were using the vaginal cream (p < or = 0.001). Patients who were receiving the vaginal tablets also had a lower incidence of patient withdrawal (10% versus 32%). CONCLUSIONS: Treatment regimens with 25-microg 17beta-estradiol vaginal tablets and with 1.25-mg conjugated equine estrogen vaginal cream were equivalent in relieving symptoms of atrophic vaginitis. The vaginal tablets demonstrated a localized effect without appreciable systemic estradiol increases or estrogenic side effects. Vaginal tablet therapy resulted in greater patient acceptance and lower withdrawal rates compared with vaginal cream therapy.

Protective effect of a thermoreversible gel against the toxicity of nonoxynol-9.

BACKGROUND AND OBJECTIVES: One major problem associated with the use of nonoxynol-9 is that it can induce local inflammation and ulceration of the vaginal and cervical mucosa that might favor the entry of pathogens. With the aim of developing a gel formulation that could be effective in preventing sexually transmitted infections, the authors have evaluated the capacity of a polyoxypropylene/polyoxyethylene polymer to reduce or eliminate the toxicity of nonoxynol-9. STUDY DESIGN: The cytotoxicity of nonoxynol-9 alone or incorporated into the gel was investigated in human cervical and colon epithelial cells and after daily intravaginal application for 2 weeks in rabbits. RESULTS: In vitro experiments showed that nonoxynol-9 was highly toxic to human cervical and colon epithelial cells in a dose-dependent manner. However, the incorporation of the spermicide into the gel markedly reduced its toxicity under the same experimental conditions. In vivo studies showed that in animals treated with nonoxynol-9, the spermicide was very toxic to the vaginal and cervical mucosa as evidenced by the presence of bleeding, irritation, epithelial disruption, necrosis, the accumulation of leukocytes in the submucosa, and the loss of integrity of the epithelial cells. Of prime importance, the incorporation of nonoxynol-9 into the gel markedly reduced the toxicity of this potent spermicide/microbicide. CONCLUSION: The gel formulation could be used as an interesting approach to eliminate the toxicity of potent spermicides/microbicides such as nonoxynol-9.

Factors associated with the obtaining of a second-trimester induced abortion.

This study investigated the factors associated with the obtaining of a second-trimester induced abortion in women consulting the Family Planning Clinic of Le Centre Hospitalier de l'Université Laval in Quebec City, between September 6, 1988 and May 11, 1990. During the study period, 2,771 women obtained abortions at between six and 16 weeks of gestation in a multidisciplinary setting. Of 18 independent variables entered in a stepwise multiple regression analysis, ten made independent contributions to explain the variance at least at the p < 0.05 level of statistical significance. Taken together, these ten variables explained 9.4% of the total variance in gestational age: being young; having a low level of education; living far from the clinic; having other children; having a sexually transmitted disease before the abortion; not using contraception or using oral contraceptives at the time of conception, or being sterilized or having a sexual partner who has had a vasectomy; having had few sexual partners in the year preceding the abortion; not having a significant relationship with a regular sexual partner; being ambivalent about the decision to abort; and having a delay between the first consultation with the clinic and the abortion.

PIP: Researchers analyzed data on 2771 women who underwent an induced abortion at the family planning clinic of Le Centre Hospitalier de l'Universite Laval in Quebec City in Canada between September 6, 1988, and May 11, 1990, to identify factors related to second trimester abortion. 281 (10.1%) women had undergone a second trimester abortion (gestational age, 13-16 weeks). 10 of the 18 independent variables in the stepwise multiple regression analysis made significant contributions to explain variance. Overall, these 10 variables explained 9.4% of the total variance. Factors associated with induced abortion at later gestational age were: being young (age 20 years) (odds ratio [OR] = 4.06; p 0.001); having less than 16 years of schooling (p = 0.013 for 13-15 years and p = 0.002 for 0-12 years); living far from the clinic (200 km) (OR = 2.04; p 0.001); having other children (p = 0.004); having had few sexual partners during the year before the abortion (OR = 1.53; p = 0.001); diagnosis of a sexually transmitted disease at the time of the abortion (p = 0.038); using oral contraceptives (OR = 2.14; p 0.001); benefiting from sterilization (OR = 1.81; p = 0.008); no contraceptive use at time of conception (OR = 1.94; p 0.001); lacking significant relationship with sexual partner (OR = 1.55; p 0.001); ambivalence about decision to undergo abortion (OR = 1.8; p 0.001); and delay between first consultation and abortion (p = 0.003). The major determinant of second trimester abortion was age (regression coefficient [RC] = 1.400; 95% confidence interval [CI] = 2.59-6.34), followed by place of residence (RC = 0.711; CI = 1.52-2.73). These results point out the importance of personal characteristics, psychological factors, and environmental influences as determinants of gestational age at the time of abortion.

The intrauterine device today.

PIP: The intrauterine contraceptive device (IUD) is effective and reversible and has a high continuation rate. It can also be used within 7 days postcoitus. Developed separately by Richter, Grafenberg, and Ota between 1909 and 1934, the IUD gained popularity in the 1960s and 1970s with the introduction of the Margulies Spiral, the Lippes Loop, the Birnberg Bow, and the Dalkon Shield. The last proved dangerous, and the IUD became unpopular. The 4 IUDs which are available in Canada include the TCu-380S (GYNE T Slimline), the TCu-200, the NOVA-T, and the Progestasert. All are T shaped and medicated (copper or progesterone). The 1st and 3rd can be left in situ for 10 years; the 2nd, for 4 years; and the 4th, for 1 year. The NOVA-T has a copper wire with a silver core and is inserted with a unique pull-push technique. The Progestasert, which contains 38 mg of progesterone, releases 65 mcg of the hormone daily. The best candidate for IUD use is parous, but not pregnant, is in a stable monogamous relationship, and has a healthy reproductive tract and no history of ectopic pregnancy, sexually transmitted disease, pelvic inflammatory disease, undiagnosed genital bleeding, endometrial or cervical neoplasia, abnormal endometrial anatomy, compromised immune system, allergy to copper, or Wilson's Disease. The only infection related to the IUD is that associated with insertion. Such an infection is polymicrobial and involves the endogenous, cervicovaginal flora (primarily anaerobes). It is usually asymptomatic and contained by the immune system. 200 mg of Doxycycline can be given orally as a prophylactic 1 hour prior to insertion. A nonprescription, nonsteroidal, anti-inflammatory drug, also taken 1 hour before the procedure, will prevent pain and a vasovagal reaction. Paracervical anesthesia should be used. If the depth of the uterus is less than 6 cm or greater than 10 cm, another form of contraception should be used. Although little research is being done in Canada on new IUDs, the Levonorgestrel IUD from Europe and the CuFix-360 (Flexigard) offer promise. The former, which is T shaped, contains polydimethylsiloxane and levonorgestrel (52 mg, total; releases 20 mcg daily) and can be used for 7 years. The latter IUD is shapeless and consists of 6 copper sleeves strung on surgical nylon thread knotted at 1 end. The knot is inserted, using a needle, into the fundal myometrium. The truth and falsehood of several myths about IUDs are noted with supporting citations.^ieng

Cycle control on low-dose oral contraceptives: a comparative trial.

Cycle control was studied comparing the monophasic oral contraceptive Loestrin with three low-dose phasic preparations (Triphasil, Ortho 10/11 and Ortho 7/7/7) in 391 women of whom 300 completed 6 cycles. Loestrin subjects had a rate of occurrence (31% of cycles) for intermenstrual bleeding (IMB) comparable to the rates for subjects on the phasic preparations (36%, 37% and 37%, respectively). Triphasil subjects had lower rates than the Ortho 10/11 and Ortho 7/7/7 subjects (p less than 0.01) in cycle one when all subjects were analyzed and in pre-study users when continuing menstrual flow (CMF) episodes were not included as IMB. IMB was a cause for dropping out of the study in 7% of subjects who were evenly distributed between groups. There were no differences between groups for BTB when perceived by subjects as a side effect. Spotting was perceived as a side effect more often with Ortho 10/11 and Ortho 7/7/7 use than with Triphasil (p less than 0.01). Loestrin, Ortho 10/11 and Ortho 7/7/7 subjects were more likely to report amenorrhea (p less than 0.001) and less likely to report leg cramps (p less than 0.01) compared to those on Triphasil. Triphasil subjects were less likely to report acne than subjects on Ortho 7/7/7 (p less than 0.01).

Validity of the Bioself 110 fertility indicator.

The Bioself 110 (Bioself Canada, Inc., Montréal, Québec, Canada) is an electronic computerized thermometer designed to identify the fertile and infertile phases of the menstrual cycle. The purpose of this study was to evaluate the validity of the device by comparing it with a reference method, the Ovustick (Monoclonal Antibodies, Inc., Mountain View, CA) luteinizing hormone (LH) surge detection kit. The Bioself 110 identified the 6-day fertile period in 86.4% of 220 cycles studied and 5 fertile days in 93.2%. The Bioself 110 correctly identified the postovulatory infertile phase in 93.3% of 178 cycles. On average, the device identified 10.9 fertile days and 10.6 postovulatory "safe" days per cycle. It was concluded the device would be a useful aid to couples trying to conceive or prevent pregnancy.

Prophylactic antibiotics for suction curettage abortion: results of a clinical controlled trial.

The prophylactic use of 300 mg doxycycline at the time of an abortion was evaluated in a randomized controlled trial. In the group with negative chlamydia screening results, only two (0.4%) of 502 patients who received prophylactic treatment developed pelvic infection, compared with 15 (3.0%) of 497 patients who received placebos (p = 0.001). The same effectiveness was found in women with positive chlamydia screening results. Vomiting was the major side effect of the medication and could limit its use. A simulation of selective prophylaxis in women with negative chlamydia screening results showed that its selective use in patients with a history of gonorrhea or in nulliparous women with multiple sex partners could be nearly two thirds as effective as general prophylaxis.

PIP: Prophylactic doxycycline (tetracycline) antibiotic was tested in a randomized, double-blind, placebo-controlled trial of 1077 women having suction curettage abortion. All women attending Laval University Hospital family planning clinic for 1st trimester abortion from November 1985 to June 1986 participated in the trial, except those eliminated because of antibiotic allergy or treatment, gonorrhea, or cardiac disease. Doxycycline was given in 100 mg capsules, 1 hour before abortion, and 2 capsules 30 minutes afterward. 2 (0.4%) women without chlamydia who received antibiotic developed pelvic infection, compared to 15 (3.0%) who received placebos (p0.001). In the group with chlamydia, 1 (3.0%) given antibiotic developed pelvic infection, compared to 11 (26.2%) given placebo (p0.009). The only side effect of the medication was vomiting in 18%. All pelvic infections were cured within 2 weeks and no antibiotic resistance was apparent. A simulation of risk factors showed that nulliparity and multiple sex partners were associated with the greatest risk of pelvic infection. Use of doxycycline in these women would be 66% as effective and twice as efficient as general prophylaxis, but prophylactic antibiotics cannot be used without follow-up and observance of specific guidelines.

Chlamydial infection among females attending an abortion clinic: prevalence and risk factors.

To determine the prevalence of Chlamydia trachomatis infection and the epidemiologic risk factors for chlamydial infection in the Quebec City region, screening was done with an enzyme immunoassay in 920 females who attended an abortion clinic between November 1985 and June 1986. The organism was detected in 105 (11.4%) of the patients. After adjustment for confounding variables, four variables were found to be independent risk factors for chlamydial infection: age 24 years or less (prevalence ratio 3.0 [p less than 0.001]), two or more sexual partners during the previous year (prevalence ratio 1.8 [p = 0.001]), no contraception or the use of a nonbarrier method (prevalence ratio 1.9 [p = 0.030]) and living in an urban area (prevalence ratio 1.6 [p = 0.046]). The results confirm that chlamydial infection is prevalent in this population. The identified risk factors may prove useful in determining the target population for screening programs.

Pregnancy after IUD use.

Much has been written about the risks of PID to IUD users, but very little about the subsequent fertility status of these patients. Is tubal infertility increased in an IUD user who has been asymptomatic? Does the addition of copper make the device harmless? Was the Dalkon Shield so harmful in the nulliparous woman? Our study (89 and 90% follow-up after 12-14 years) of 200 Dalkon Shield and 142 TCu-200 users allows us to answer 'No' to the three previous questions. We conclude that wearing an IUD per se does not cause infertility since all our patients who had IUDs removed for intended pregnancy did become pregnant; the addition of copper per se does not make an IUD safer although it does make it more efficient; the Dalkon Shield used in nulligravidas was not more dangerous than other types of IUD.

Long-term study of the safety of the Dalkon Shield and Gyne-T 200 intrauterine devices.

Between 1971 and 1973, 200 Dalkon Shield and 142 Gyne-T 200 intrauterine devices (IUDs) were inserted at the department of obstetrics and gynecology in a large urban hospital. In 1984 retrospective analysis of events associated with the use of these IUDs was done. Hospital and clinic charts were reviewed, and the women were contacted to obtain information on infertility and the outcome of pregnancy after discontinuation of IUD use. The rates of events leading to discontinuation of IUD use 2 years after insertion were similar in the two groups except for that of planned pregnancy, which was higher in the Dalkon Shield users (p less than 0.05). The rates of accidental pregnancy per 100 women were 3.8 for the Dalkon Shield users and 1 for the Gyne-T 200 users. The rates of pelvic inflammatory disease (PID) based on all cases of PID and follow-up information were similar in the two groups. There were no differences between the two groups in outcome of pregnancy with the IUD in situ or after expulsion or removal of the IUD because of planned pregnancy or other reasons. Infertility rates after discontinuation of IUD use were similar for the Dalkon Shield and Gyne-T 200 users. The results confirm the authors' opinion that the Dalkon Shield and Gyne-T 200 IUDs are safe and effective methods of intrauterine contraception.

[Not Available]. / La ménopause: subir, prévenir ou guérir.

The menopause is one of the clinical manifestations of the climacteric. It is a sure sign of diminishing ovarian function and the hormonal deficiency which stems from it. Premenopause is characterized by a progesterone insufficiency which manifests in menstrual irregularity and menometrorrhagia. Treatment with progesterone replacement alone is most often sufficient. Menopause is the cessation of menstruation, sometimes without other symptoms. Immediate postmenopause is the most difficult period to live through; symptoms arise from the disappearance of ovarian secretions and an estrogen/progesterone replacement is necessary. Late postmenopause is sometimes complicated by osteoporosis, which estrogen helps prevent, but calcium should be added for greater effect. It is preferable to prevent the harmful effects of the menopause rather than cure the pathological consequences.

Prediction of human ovulation by rapid luteinizing hormone (LH) radioimmunoassay and ovarian ultrasonography.

Accurate prediction of the time of ovulation is essential for the recovery of a mature oocyte for in vitro fertilization (IVF). The preovulatory luteinizing hormone (LH) surge can be considered the most reliable hormonal change closely related to ovulation. With the use of a rapid LH assay and ovarian ultrasonography, it now appears possible to predict quite accurately the time of ovulation, provided that these technologies are appropriately applied. Therefore, we have used a newly standarized rapid (3-hour) LH radioimmunoassay (RIA) for serial estimation of preovulatory serum LH surge. So far, 21 women have come to our center daily during their 5-day preovulatory period. Blood samples were taken daily every 3 to 5 hours between 7:00 A.M. and 11:00 P.M. Ovarian ultrasonic scans were performed one to three times daily depending on the day of the cycle and the serum LH level. Data show that there is a significant variation in the mean preovulatory follicular size, in the duration of the LH surge, and in the time interval between the initial rise of LH surge and the estimated time of ovulation. Results obtained from six women studied during two to four cycles indicate that each woman has a distinctive hormonal and ultrasonic pattern that appears to be reproducible. Thus it is recommended that such a pattern be appropriately evaluated before attempting laparoscopy for recovery of a mature human oocyte.