Association between COVID-19 and vaccination on menstrual cycle.

OBJECTIVE: To evaluate changes in the menstrual pattern of women of reproductive age infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or vaccinated against coronavirus disease 2019 (COVID-19). METHODS: A cross-sectional study at the University of Campinas, Brazil using Google questionnaire applied from December 2021 through February 2022, disseminated through snowball technique. Participants responded about characteristics of their menstrual cycle before the pandemic and before COVID-19 vaccination, and then about characteristics of their cycle 3 months after infection with SARS-CoV-2 and 3 months after vaccination. Our primary outcome was a binary indicator of changes in the menstrual cycle. We used multivariate regression analysis to identify factors associated with menstrual changes. RESULTS: We received 1012 completed questionnaires and 735 (72.7%) were from women aged between 20 and 39 years, 745 (73.6%) were White and 491 (48.6%) lived with a partner. A total of 419 (41.6%) of the women reported SARS-CoV-2 infection; however, only two of them were hospitalized, and 995 (98.8%) of women had at least one dose of COVID-19 vaccine. About menstrual characteristics, 170 (41.3%) reported changes after having COVID-19 and 294 (29.9%) after COVID-19 vaccination, respectively. Few years of schooling, lower income, and non-white ethnicity were related to higher reports of menstrual changes after COVID-19. Menstrual changes after COVID-19 vaccination were associated with not using contraception. Higher body mass index was associated with irregularities in cyclicity and bleeding days, after COVID-19 and COVID-19 vaccination, respectively. CONCLUSION: Our results corroborated the stability of the menstrual cycle after having COVID-19 or COVID-19 vaccination; however, there is a potential relationship between menstrual changes and socioeconomic factors as well as contraceptive use.

Diagnostic value of susceptibility-weighted imaging of abdominal wall endometriomas during the cyclic menstrual changes: a preliminary study.

OBJECTIVE: The purpose of this study is to investigate the value of susceptibility-weighted imaging (SWI) for the evaluation of cyclic morphological and hemorrhagic changes in abdominal wall endometriomas (AWE). MATERIALS AND METHODS: Fourteen patients with a total of 17 lesions who were admitted with complaints of abdominal wall mass and cyclic pain were evaluated by MRI. Patients were scanned during the first three days of the menstrual cycle and during the mid-cycle phase (day 13-15). In addition to conventional images SWI was performed. The signal changes within the lesions on SWI were compared and graded on both studies. RESULTS: There was no significant difference in the size of the lesions in the early days of the menstruation compared to the mid-menstrual period. The SWI taken on mid-cycle phase showed that the center was hyperintense and the peripheral zone was hypointense in all lesions. A signal void related to increased blood and the shrinkage of complete disappearance of hyperintensity in the venter of the lesion was seen 15 (88%) of the 17 cases on the SWI series performed during the menstrual phase scan. CONCLUSION: SWI is a sensitive technique and has the capability to show hemorrhage and deposition of hemosiderin within the lesions. For patients suspected with AWE, valuable diagnostic findings may be obtained if the MRI examination including SWI is performed during the early and mid phase menstrual cycle.

Use of levonorgestrel implants versus oral contraceptives in adolescence: a case-control study.

OBJECTIVE: We compared continuation rates, effectiveness, satisfaction with method, side effects, and condom practices among adolescents using levonorgestrel implants (Norplant, Wyeth-Ayerst Laboratories, Philadelphia) as compared with oral contraceptives. STUDY DESIGN: We conducted a case-control study comparing 94 adolescents < or = 18 years old who received Norplant between March 1, 1992, and Nov. 1, 1993 (cases), with 94 age-matched controls who selected oral contraceptives during this same time period. By use of a structured questionnaire, information was obtained on pregnancy status, duration of use, patient satisfaction, side effects, and condom practices 6 months after initiation. Objective measures included weight on Norplant and oral contraceptive users and hematocrit on implant patients. RESULTS: Forty (43%) oral contraceptive patients compared with no Norplant patients discontinued their selected method before the 6-month interview (p = 0.00). Six patients prescribed oral contraceptives became pregnant. Ninety-three percent of Norplant users expressed overall satisfaction despite experiencing menstrual irregularity and cramping, amenorrhea, nervousness, abnormal hair growth or loss, rashes, and an increase in appetite more often than oral contraceptive users. Although Norplant patients also reported an increase in the duration of menstrual flow and number of days of spotting more often than oral contraceptive users, evaluation of hematocrits in these patients demonstrated a significant increase over the 6-month period (p = 0.00). Assessment of condom practices since initiation demonstrated that Norplant patients used condoms less often than oral contraceptive users (p = 0.00). CONCLUSION: Use of levonorgestrel implants may cause more side effects than oral contraceptives in the early months after initiation but provide superior protection against unintended pregnancy. We concluded that Norplant is a reasonable alternative for adolescents, especially when compliance is an issue.

Epidemiology of menstruation and its relevance to women's health.

PIP: The data on the menstrual cycle as a health endpoint and as a risk factor for chronic disease are inadequate. Specifically, the data on menstrual cycle length and blood loss do not have the detail on within-woman variability needed to allow women and clinicians to anticipate certain bleeding changes that tend to develop at different life stages, to distinguish between potentially pathologic alterations from short-term aberrations, and to recognize bleeding patterns that may be risk factors for the development of chronic disease. Lack of data on bleeding changes in premenopausal and menopausal women concerns many health professionals considering the many physician visits for abnormal bleeding and the prevalence of hysterectomy among women aged more than 35. Thus, development of objective criteria on how much bleeding is too much is needed so women can determine whether their daily blood loss is or is not a concern. Women also need more information on what constitutes menstrual dysfunction. Some basic research needs include definition of population patterns of gynecologic disease, identification of potentially modifiable risk factors, the influence of recreational activity in gynecologically mature women, influence of hard physical activity in the context of women's daily work life, interaction of low weight and physical activity in developing countries, effects of work stress, effects of family interactions, effects of violence, environmental risk factors (e.g., pesticides), and physiologic variation across the menstrual cycle. Research on menstrual cycle-related risk factors for chronic disease could explain women's long term health status and identify preventive strategies for premenopausal women. Current women's health research tends to ignore hormonal influences. The limited available research on immune parameters suggests that follicular/luteal classification may not be able to detect meaningful variation. In conclusion, a comprehensive research program would fill the many gaps in scientific knowledge about the menstrual cycle.^ieng

Effect of tamoxifen alone and in combination with RU 486 on the endometrium in the mid-luteal phase.

The effects of RU 486 combined with tamoxifen and tamoxifen alone on hormonal parameters and endometrial development at the time of implantation were studied. Measurements of cytosolic oestrogen and progesterone receptors in endometrium and placental protein 14 (PP14) in plasma were also included. Three dosage schedules were used: single oral dose of 40 mg tamoxifen alone and in combination with 200 mg RU 486, and 40 mg tamoxifen for three consecutive days starting on the first day after the luteinizing hormone (LH) surge. The combined treatment prolonged the luteal phase (P < 0.05) and increased the plasma levels of progesterone. A single dose of tamoxifen did not affect the bleeding pattern and plasma hormone levels, but raised plasma oestradiol and LH with the 3-day treatment. The endometrium was retarded after the combined and the 3-day treatment with tamoxifen. Concentrations of cytosolic progesterone receptors were higher after the combined therapy, but were unaffected after tamoxifen only. PP14 levels were higher (P < 0.05) after repeated tamoxifen doses than in controls, but were lower with combined treatment. Progesterone and oestrogen are evidently necessary for endometrial maturation during the secretory phase of the menstrual cycle. PP14 levels in plasma cannot be used for clinical assessments of endometrial function because high levels coincide with disturbed endometrial development.

Effects of continuous treatment with low dose mifepristone throughout one menstrual cycle.

The effects of continuous low dose mifepristone (RU 486) 10, 5 or 1 mg/day on the menstrual cycle were assessed in groups of five volunteers, who were treated for 30 days from the beginning of the cycle. Hormonal determinations in blood and urine samples, ovarian ultrasonography and an endometrial biopsy taken on day 22-29 of treatment were used to monitor the cycle. Pre- and post-treatment cycles presented a normal profile. During treatment, concentrations of RU 486 in plasma ranged from 65 nmol/l with 1 mg/day to 1000 nmol/l with 10 mg/day. With 10 or 5 mg/day, all treated cycles were prolonged as a result of arrested or slower follicular growth during treatment. Gonadotrophins, sex steroids and their urinary metabolites remained at early follicular phase levels throughout treatment, whereas androstenedione, prolactin and cortisol were unaffected. Follicular maturation resumed after discontinuation of treatment and several days later a luteinizing hormone surge followed by a luteal phase was observed in all cases. Ovulation was suppressed during treatment only in one of the five cycles treated with 1 mg/day. Endometrial maturation was disturbed by all doses. These data demonstrate a differential threshold of the follicle and the endometrium to mifepristone. This finding has potential application in the contraceptive field.

The impact of HIV on women: gynecology, pregnancy, and family planning considerations.

PIP: Few studies of the course of HIV infection or response to treatment for women with HIV exist. There have been studies on women's role in transmission of HIV to sexual partners and to infants, however. The experiences of homosexuals forms our knowledge base about HIV infection, yet as of April 1992, 22,000 women had AIDS. Most lived in inner cities on the East Coats of the US. Black and Hispanic women suffer from HIV infection rates 13 and 6 times higher, respectively, than that of white women. Despite the large number of HIV-infected women, many health providers and policymakers still believe that AIDS does not affect women, health workers tend to overlook AIDS symptoms in women or attribute them to other causes, and women tend to place other's need over their own. Thus biological and social factors cause women with HIV/AIDS to fall and die sooner than men. Even though HIV contributes to and/or alters gynecological conditions, infectious disease specialists do not perform pelvic examinations and reproductive health practitioners do not know much about HIV detection or management. These gynecological manifestations include genital ulcers, human papillomavirus infection, cervical cancer, pelvic infection, candidiasis, and changes in the menstrual cycle. Women are often not empowered to negotiate condom use and to request sexual abstinence. Safe, reliable, and acceptable contraceptive methods must be available for HIV-positive women. They should avoid IUDs, however, since IUDs increase susceptibility to pelvic infections. HIV-positive pregnant women face unique problems such as consideration of pregnancy termination since vertical transmission is likely, struggles with religious beliefs, and locating health practitioners to provide them with prenatal care. Research is needed on the biological, psychological, social, and sexual effects of HIV on women. Community-based primary health care facilities can meet the needs of women infected with HIV.^ieng

Hormonal profile of the menstrual cycle in Chinese women after tubal sterilization.

Ten women after tubal sterilization were studied for the hormonal profile of the menstrual cycle. They had undergone sterilization procedures, on the average 5.3 years (range 1.5-10 years) earlier. The serum concentrations of LH, FSH, prolactin, estradiol and progesterone were measured by RIA in daily blood samples of a complete menstrual cycle. Another ten normal women were studied at the same time and were used as the control group. There were no significant differences in the hormonal patterns of the menstrual cycle between the two groups. There was a significantly lower LH level in the early luteal phase of the tubal ligation group compared to the control group. Also, a significantly lower E2 luteal peak compared to the preovulatory peak was observed in the tubal ligation group. The physiological significance of these minor changes is not clear. Only one out of ten women in the tubal ligation group, who had undergone sterilization 1.5 years prior, showed a deficiency in luteal function, but her ovulatory function and menstrual cycle appeared normal. This study indicates that normal hormonal profiles are retained after tubal sterilization.

PIP: 10 women were studied poststerilization for the hormonal profile of the menstrual cycle. They had undergone the procedures on an average of 5.3 years earlier (range 1.5-10 years). The serum concentrations of luteinizing hormone (LH), follicle stimulating hormone, prolactin, estradiol, and progesterone were measured by radioimmunoassay in daily blood samples of a complete menstrual cycle. Another 10 normal women were studied at the same time and were used as a control group. There were no significant differences in the hormonal patterns of the menstrual cycle between the 2 groups. There were significantly lower LH levels in the early luteal phase of the tubal ligation group as compared to the controls. Also, a significantly lower E2 luteal peak compared to the preovulatory peak was observed in the tubal ligation group. The physiological significance of these minor changes is not clear. Only 1 of 10 women in the tubal ligation group who had undergone sterilization 1.5 years earlier showed a deficiency in luteal function however, her ovulatory function and menstrual cycle appeared normal. This study indicates that normal hormonal profiles are retained after tubal sterilization.

Hormonal and menstrual changes after laparoscopic sterilization by Falope-rings or Filshie-clips.

OBJECTIVE: To evaluate the influence of laparoscopic sterilization by Falope-rings (Cabot Medical Corp., Langhorne, PA) or Filshie-clips (Femcare, Nottingham, United Kingdom) on menstrual pattern and ovulatory function. DESIGN: A prospective, nonrandomized study of women sterilized by Falope-rings (n = 6) or Filshie-clips (n = 5). Menstrual charts were kept. Serum follicle-stimulating hormone (FSH), estradiol (E2) and progesterone (P) were measured by means of radioimmunoassay in one cycle before and 3, 6, and 12 months after the sterilization. Blood samples were drawn on day -6, -2, 0, +6, +10 of the menstrual cycle, ovulation corresponding to day 0. The women sterilized by Filshie-clips had abdominal ultrasonography of the ovaries measuring the leading follicle on day -6, -2, 0, +6 of the menstrual cycle. PATIENTS: Twelve women, 25 to 38 years old, with regular menstrual cycles and no use of oral contraceptives or intrauterine contraceptive device at least 6 months before sterilization. One woman was excluded. RESULTS: After the sterilization, all women reported unchanged menstrual pattern. The follicular rise in E2 unchanged, and FSH levels fell accordingly. Progesterone levels were ovulatory, but the midluteal P peak 3 months poststerilization was significantly decreased. Serial abdominal ultrasonography in women sterilized by Filshie-clips confirmed ovulation in all cycles except in one woman, who had an unruptured follicle in one cycle before and in the sixth cycle after sterilization. CONCLUSION: Laparoscopic sterilization by Falope-rings or Filshie-clips does not seem to interfere with menstrual pattern or ovulatory function.

PIP: Physicians evaluated the effect of laparoscopic female sterilization by Falope-ring and the Filshie-clip technique on the menstrual pattern, the ovarian endocrine function, and the ovulatory function on 6 women at the Rigshospitalet in Copenhagen, Denmark and on 5 women at Gentofte County Hospital in Denmark. They followed these women from 1-2 months before sterilization and at 3,6, and 12 months after sterilization. The physicians took blood samples on day -6, -2, 0 (menstrual cycle), 6, 10 of the menstrual cycle to measure follicle stimulating hormone (FSH), estradiol, and progesterone. Ultrasonography measured the leading follicle of women sterilized by Filshie-clips on day -6, -2, 0, 6, 10 of the menstrual cycle. None of the 11 25-38 year old women used oral contraceptives or an IUD before the surgery. All experienced regular menstrual cycles. The sterilization did not cause any changes in menstruation. Moreover peak estradiol levels rose during the follicular phase and peak FSH levels decreased as normal. Overall peak progesterone levels stayed within normal limits of the ovulatory cycle, but it fell considerably 3 months after sterilization (p.05) and somewhat significantly 12 months after sterilization. Ultrasonography revealed that only 1 women sterilized by Filshie-clips experienced an unruptured follicle in the cycle before and the 6th cycle after sterilization. All other women sterilized by Filshie-clips experienced normal valuation. Based on these results, the researchers concluded that laparoscopic female sterilization by Falope-rings and the Filshie-clips do not affect the menstrual pattern or ovulatory function.

[Effects of oral contraceptive norethisterone compound on lipid and lipoprotein metabolism].

PIP: 20 healthy women in their reproductive age were treated orally with norethisterone, beginning with the 5th day of the menstrual cycle. Each patient received 1 pill each day, 22 pills/cycle, for a total of 6 cycles. Lipid levels, including triglyceride (TG), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), apolipoprotein AI (apo AI), apolipoprotein AII (apo AII), and apolipoprotein B (apo B), were determined in fasting fresh serum prior to treatment, after treatment for the 1st and for the 6th cycle, as well as in the 3rd cycle after cessation of treatment. Results show that all parameters except LDL-C increased significantly (p0.05-0.01) after treatment for the 1st cycle. All parameters were continuously increasing (p0.01-0.001) after treatment for 6 cycles. After cessation for 3 cycles, TG, TC, and LDL-C levels all returned to normal. Although all others had a tendency to decrease, they were still significantly higher than the levels prior to treatment (p0.05-0.01). During the entire study period, except for the fact that the ratio of apo AI/AII increased significantly (p0.05) after treatment for 1 cycle, the changes of other ratios were all insignificant. The study suggests that norethisterone induces a change in lipid metabolism, but no changes occur in the ratios. Thus it can be concluded that there is no obvious relation between norethisterone and CVD. (author's modified)^ieng

Desogestrel-ethinylestradiol, an oral monophasic contraceptive. Clinical and lipid metabolic effects: a 5-year experience.

A comparative study of 5 years' duration using desogestrel (DSG), levonorgestrel (LN), and norethindrone (NET), combined with ethinyl estradiol (EE), was conducted. A total of 4499 cycles on DSG-EE, 3691 on LN-EE (1980 on triphasic and 1711 on monophasic schemes) and 1680 on NET-EE was evaluated. A contraceptive efficacy of 100% was obtained in all the groups. Minimal side effects were observed. In particular, body weight in those women on DSG-EE did not show noticeable changes and headaches were minimal. No alterations on blood pressure readings or on the routine laboratory tests were noticed in any of the groups. There was a significant increase in high-density lipoprotein-c (HDL-c) in women on DSG-EE. There was no change in NET-EE, and a significant decrease in women on LN-EE in both schemes. Changes in LDL-C, very low density lipoproteins, triglycerides, total lipids, total cholesterol, and glucose were not significant, although there was some increase at 60 cycles on triglycerides on those women on DSG-EE and on NET-EE. At the end of 5 years, 76% of women continued on DSG-EE. They indicated their satisfaction with this method.

Contraception after heart surgery.

This study represents the different methods of contraception used by women having cardiac surgery at Ain Shams University Hospital. The study comprised of 250 women having had mitral commissurotomy, 77 women having had valve replacement including one case of triple valve repair and 3 women having had cardiac surgery for congenital heart disease. An IUCD was used by 170 women (51.5%), vaginal tablets by 4 women (1.2%), oral contraceptive pills by 7 women (2.1%), "safe period" by 7 women (2.1%), tubal ligation was performed in 10 women (3%). The husbands of 33 women (10%) used condoms, and 99 women (30%) did not use contraceptive methods. The IUCD was tolerable and was associated with bleeding in 60 women (35.2%) and leucorrhoea in 55 (32.3%). The IUCD was removed from only one woman due to severe bleeding. Three pregnancies occurred with condom users in two women who had had mitral commissurotomy and one having had valve replacement. There was no case of bacterial endocarditis in the study group.

PIP: Different methods of contraception used by women undergoing cardiac surgery at the Ain Shams University Hospital in Cairo are discussed. The study including 250 women who had mitral commissurotomy, 77 with valve replacement including 1 case of triple valve repair, and 3 women who had cardiac surgery for congenital heart disease. An IUD was used by 170 women (51.5%), vaginal tablets by 4 (1.2%), oral contraceptives by 7 (2.1%), "safe period" by 7 women (2.1%), and tubal ligation was performed on 10 women (3%). The husbands of 33 women (10%) used condoms, and 99 women (30%) did not use any contraception. The IUD was tolerable, and was associated with bleeding in 60 women (35.2%) and leukorrhea in 55 (32.3%). The IUD was removed from only 1 woman because of severe bleeding. 3 pregnancies occurred with condom users in 2 women who had had mitral commissurotomy and 1 who had valve replacement. There was no incidence of bacterial endocarditis in the study group.

Clinical evaluation of a new triphasic oral contraceptive: norgestimate and ethinyl estradiol.

The safety and efficacy of the triphasic oral contraceptive agent containing norgestimate and ethinyl estradiol were evaluated in a 12-month study of 661 women. Excellent contraceptive efficacy was achieved, with two pregnancies ascribed to product failure in a total of 6,511 treatment cycles. The life-table predicted pregnancy rate was 0.57 per 100 woman-years of use. The overall and theoretical Pearl indexes were 0.55 and 0.37, respectively. Good cycle control was maintained in patterns similar to those noted in previous studies. The incidence of dysmenorrhea and premenstrual syndrome was sharply reduced. Side effects reported were typical of those associated with use of low-dose oral contraceptive agents. Acceptability was high compared with agents used previously by the subjects. Total cholesterol did not change but high-density lipoprotein cholesterol was significantly elevated at 3 and 12 months. There were no clinically significant changes in the parameters of hematology or blood chemistry tested.

PIP: The safety and efficacy of the triphasic oral contraceptive (OC) containing norgestimate and ethinyl estradiol were evaluated in a 12-month study of 661 women. Excellent contraceptive efficacy was achieved, with 2 pregnancies ascribed to product failure in a total of 6511 treatment cycles. The life-table predicted pregnancy rate was 0.57/100 woman-years of use. The overall and theoretical Pearl indexes were 0.55 and 0.37, respectively. Good cycle control was maintained in patterns similar to those noted in previous studies. The incidence of dysmenorrhea and premenstrual syndrome was sharply reduced. Those side effects reported were typical of those associated with use of low-dose OCs. Acceptability was high compared with OCs used previously by these subjects. Total cholesterol did not change but high-density lipoprotein cholesterol was significantly elevated at 3 and 12 months. There were no clinically significant changes in the parameters of hematology or blood chemistry tested.

Cycle control with triphasic norgestimate and ethinyl estradiol, a new oral contraceptive agent.

Effective cycle control was demonstrated based on two multicenter, 2-year studies of the triphasic oral contraceptive (OC) agent containing the new progestin norgestimate. The estrogen in this OC is ethinyl estradiol. These open-label Phase III studies were conducted in the United States by 33 investigators at 33 sites who treated a total of 1,783 subjects, healthy women 17 to 38 years of age with menstrual cycle characteristics considered to be within the normal range. The norgestimate/ethinyl estradiol preparation was taken for up to 24 cycles. Follow-up information was collected 3 to 4 months post-treatment. Bleeding pattern analyses were based on 27,970 valid cycles. Normal cyclic bleeding patterns were experienced by most of the women during the study; only minimal and statistically and clinically insignificant variations in menstrual flow, dysmenorrhea, and premenstrual tension occurred. There was a low incidence of failed withdrawal bleeding in single cycles (less than 1.0% after cycle 6). There were no cases of amenorrhea, defined as two consecutive cycles of missed withdrawal flow. The incidence of breakthrough bleeding or spotting was highest during the initial treatment cycles and diminished with continued use of the formulation. The mean incidence of breakthrough bleeding was 2.36% in cycles 13 to 24. Apart from somewhat higher initial percentages among women new to oral contraception, the pattern of midcycle bleeding or spotting was similar to that of all women studied. Effective long-term cycle control was demonstrated in women who used this OC agent.

Long-term use of depot-norethisterone enanthate: effect on blood coagulation factors and menstrual bleeding patterns.

Fifty-six women using depot-norethisterone enanthate injections for contraception for 2 years or more were compared with a control group of 48 women not using hormonal contraception. No significant difference was found between the study group and controls for Factors VIIc and Antithrombin III. Factor Xc was reduced in women who had used the injections for over two but less than five years [controls: mean 90.3% SD31.2 vs users for 2-5 yr: 78.7% SD17.1, 95%CI difference in means -0.3, -22.9]. In the group using Net-En for five years or more, Factor Xc was significantly higher than in the control group, but only by 14% of the mean control value [users for over 5 yr: 103.2% SD15.2, 95%CI difference in means 3.1, 22.7]. Haemoglobin levels, red cell count and packed cell volume were higher in those using the injections than in the control group. Changes in the platelet count were not statistically significant. Twenty-three women using the injection agreed to keep menstrual diaries. Of these, 20 experienced amenorrhoea for more than two consecutive injection intervals (112 days). It is concluded that long-term use of norethisterone enanthate is not associated with any markedly deleterious effects on Factor VIIc, Xc, or antithrombin III or haemoglobin levels. Amenorrhoea of 4 months or more can be expected after two years of continuous use.

A comparative study of 35 mcg and 50 mcg combined oral contraceptives: results from a multicenter clinical trial.

A comparative multicenter clinical trial of two combined oral contraceptives (OCs) differing only in the estrogen content (35 mcg ethinyl estradiol versus 50 mcg mestranol) was conducted at five clinics located in Yugoslavia, Egypt, Sri Lanka, Costa Rica and Mexico. The trial was designed to determine the differences between Norinyl 1+35 (Syntex) and Norinyl 1+50 (Syntex) in rates and reasons of discontinuation, and frequency of selected side effects which might contribute to method discontinuation. This report includes analysis of 1698 women, all of whom were interval patients (at least 42 days but within 26 weeks postpartum), randomly allocated to one of the above OCs between October 1982 and January 1984. Follow-up visits were scheduled at 1, 4, 8 and 12 months after admission. Significantly more women in the Norinyl 1+35 group (p less than .001) reported intermenstrual bleeding (primarily staining and spotting), as well as an increase in the occurrence of intermenstrual bleeding compared to women in the Norinyl 1+50 group. There were no significant differences between the groups for side effects with the exception of more women in the Norinyl 1+50 group (p less than .05) reporting breast discomfort. The lost to follow-up rate at 12 months was 19.3% for both the Norinyl 1+35 and the Norinyl 1+50 groups. The total discontinuation rate (including women lost to follow-up) at 12 months was 43.5% for the Norinyl 1+35 group and 41.0% for the Norinyl 1+50 group. There were no significant differences between the two groups for gross cumulative life table discontinuation rates (p greater than .05). There were six accidental pregnancies attributed to user failure reported during the study period; four in the Norinyl 1+35 group and two in the Norinyl 1+50 group.

Oral contraceptive (OCP) use increases proliferation and decreases oestrogen receptor content of epithelial cells in the normal human breast.

The effect of ingestion of oral contraceptives (OCP) on cell proliferation and oestrogen (ER) and progesterone receptor (PR) expression of the epithelial cells of the normal human breast was compared with findings in controls not taking OCPs. Histologically normal breast tissue was removed during operation for fibroadenoma or reduction mammoplasty in 216 women whose mean age was 28.1 +/- 8.5 years (+/- SD range 14-53 years). During natural cycles the mean proportion of cells expressing ER was 3.94 +/- 3.71 (% mean +/- SD, range 0-20.8, n = 51), while of those expressing PR it was 12.1 +/- 7.1% (range 3.0-36.1, n = 47). There was a significant decline in ER during the menstrual cycle [p = 0.001 by multiple linear regression (MLR)], but there was no significant change in the proportion which expressed PR. The mean proportion of proliferating cells (LI) was 2.50 +/- 2.42 (range 0-11.5, n = 147). There was a significant increase of LI during the cycle (p = less than 0.001, MLR) and a significant inverse relationship between LI and ER (r = -0.29, p less than 0.01). Use of the OCP significantly reduced the number of cells which expressed ER and increased the LI earlier in the cycle. No effect of OCP use on the number of PR+ cells was detectable. We conclude that significant changes in the proportions of ER+ and proliferating cells occur during natural menstrual cycles. These changes are perturbed by ingestion of OCPs, so that there is greater suppression of ER and a longer period of high proliferation during the menstrual cycle. These results may explain the relationship between OCP use and the possible risk of breast cancer.

Open prospective multicenter trial with a new monophasic contraceptive combination containing gestodene.

In a large and open prospective multicenter trial of 12,250 cycles from 2,378 women, contraceptive efficacy, clinical tolerance and acceptability of a new monophasic contraceptive combination containing 75 mcg gestodene (delta-5-levonorgestrel) and 30 mcg ethinyl oestradiol were studied. The objective was to assess efficacy, safety, side effects and cycle control of this oral contraceptive on healthy women using no other additional birth control methods. Two women became pregnant (0.016%) during the trial; both were patient failures. There was no effect on systolic or diastolic pressures. An average weight increase of 0.3 kg was noted. Cycle control was excellent with 95% of the cycles free of spotting and 98% free of breakthrough bleeding after six cycles. No serious complications occurred. There was an overall incidence of 14% reported side effects (after six cycles), indicating that the hormonal combination is well tolerated. It should be noted that 41.4% of the patients had some complaint before starting the treatment. For all complaints, a highly significant improvement was seen during the treatment.

PIP: In a large and open prospective multicenter trial of 12,250 cycles from 2378 women, contraceptive efficacy, clinical tolerance, and acceptability of a new monophasic oral contraceptive (OC) containing 75 mcg gestodene (delta-5-levonorgestrel) and 30 mcg ethinyl estradiol (EE) were studied. The objective was to assess efficacy, safety, side effects, and cycle control for this OC on healthy women using no other additional birth control methods. 2 women became pregnant (0.016%) during the trial; both were patient failures. There were no side effects on systolic or diastolic pressure. An average weight increase of 0.3 kg was noted. Cycle control was excellent with 95% of the cycles free of spotting and 98% free of breakthrough bleeding after 6 cycles. no serious complications occurred. There was an overall incidence of 14% who reported side effects after 6 cycles, indicating that the hormonal combination is well-tolerated. It should be noted that 41.4% of the patients had some complaint prior to the start of treatment. For all complaints, a highly significant improvement was seen during treatment.

Lysosomal enzymes in the human endometrium: a biochemical study in untreated and levonorgestrel-treated women.

The activities of four lysosomal enzymes, i.e. N-acetyl-beta-hexosaminidase, acid phosphatase, alpha-D-mannosidase and alpha-L-fucosidase have been measured in extracts of endometrial biopsies from untreated and levonorgestrel-treated women of fertile age. Values were compared with protein and DNA content, as well as with lactate dehydrogenase activity, used as reference constituents. In parallel, organ cultures were established from the same endometrial specimens and the release of lysosomal enzymes into the medium was followed. The human endometrium possesses a rich lysosomal equipment, comparable to that found in the human liver. In the untreated cycles, the activities of lysosomal enzymes show a coordinate response to the hormonal changes, decreasing by about 40% from the proliferative to the mid-late secretory phase. Long-term levonorgestrel treatment causes a marked cytoplasmic atrophy, as shown by decreased protein content and lactate dehydrogenase activity, whereas DNA content remains unchanged. In contrast, N-acetyl-beta-hexosaminidase, one of the most active lysosomal enzymes studied, shows a higher specific activity upon levonorgestrel. In both untreated and treated endometria, the organ cultures provide biochemical evidence for a higher release of N-acetyl-beta-hexosaminidase than of lactate dehydrogenase, indicating active secretion of the lysosomal enzyme. During levonorgestrel treatment, there was no correlation between clinically recognized spotting-bleeding patterns and lysosomal enzyme content in, or release from, the endometrium.

Clinical experience with triphasic oral contraceptive (Triquilar) in 527 women in China.

From October 1987 to May 1989, a total number of 527 women completed a total of 6,291 treatment cycles in 6 centers in China for the study of a triphasic oral contraceptive - Triquilar. The mean age of subjects was 30.21 +/- 2.84 years. There were 7 pregnancies during the study period. Among them, five were patient failures because of missed pill or incorrect intake; one had taken barbiturates along with Triquilar. Only one woman became pregnant in the 11th treatment cycle without any reason being found. In most cases, menstrual flow decreased and dysmenorrhea improved as treatment continued. Of the total treatment cycles, the incidence of missed withdrawal bleeding was 0.25%, spotting 0.97%, and breakthrough bleeding 0.48%. Nausea and vomiting was the most common side effect and accounted for 6.4% of the total treatment cycles. This was followed by breast tenderness (3.7%), dizziness (2.4%) and headache (1.6%). Most of the side effects occurred during the first few cycles and were alleviated later. By the end of one year, the total dropout was 64 cases. The reasons for discontinuing treatment were: pregnancy 1.33 (per hundred women), menstrual disturbances 0.76, side effects 3.80, other medical reasons 2.09, and personal reasons 4.18. The results confirm that Triquilar is an effective oral contraceptive with good cycle control and low incidence of side effects. No serious reaction has been reported. It has been well accepted by the Chinese women. However, due to the low dosage of steroids, it is of utmost importance to avoid errors in its use.(ABSTRACT TRUNCATED AT 250 WORDS)