Combined contraceptive ring versus combined oral contraceptive (30-µg ethinylestradiol and 3-mg drospirenone).

OBJECTIVES: To compare the adverse effects, cycle control, and metabolic effects of NuvaRing and a combined oral contraceptive (COC). METHODS: Women seeking contraception received NuvaRing (n = 300) or a COC (n = 300) for 12 cycles in a randomized, open-label trial. RESULTS: The total number of women with adverse effects did not differ significantly between the 2 groups. Leucorrhea, vaginitis, decreased libido, and ring-related problems were more common with NuvaRing, whereas weight increase, acne, and emotional lability were more common with the COC. Breakthrough bleeding occurred in 11.3% of women receiving NuvaRing and in 14.7% of women receiving the COC; 2.1% and 2.9% of women, respectively, had no withdrawal bleeding. Differences in blood pressure, blood sugar levels, lipid profile, liver enzyme activity, and anticoagulant activity were not statistically significant, with the exception of low-density lipoprotein levels measured at 6 and 12 months, which were significantly lower in the NuvaRing group than in the COC group. CONCLUSIONS: NuvaRing is a good alternative to a COC. It is associated with a slightly reduced incidence of breakthrough bleeding and there were no clinically relevant adverse effects or changes in blood pressure, blood sugar levels, lipid profile, or anticoagulant activity when compared with the COC.

Urogenital effects of selective estrogen receptor modulators: a systematic review.

OBJECTIVE: Selective estrogen receptor modulators (SERMs) include a relatively large number of compounds, each with different profiles of estrogenic/antiestrogenic actions on the genital tract. The aim of this review was to systematically evaluate all the available data from randomized, controlled studies on the effects of these compounds on pelvic organ prolapse and urinary incontinence. METHODS: Literature searches were performed using three computerized databases to identify the result of all randomized, controlled trials performed with SERMs having any effects on pelvic floor as an outcome. A manual search was performed on all related articles. RESULTS: We have identified only one randomized, placebo-controlled trial specifically designed to assess the effect of raloxifene and tamoxifen on the urogenital tract. Most of the data on genitourinary effects of various compounds derive from either questionnaires or adverse events reported during phase III clinical trials. Both tamoxifen and raloxifene appear to increase the incidence of pelvic floor prolapse in one trial, although this was not apparent from the licensing studies data for either of the drugs. Raloxifene does not appear to increase the incidence of urinary incontinence. Levormeloxifene and idoxifene, on the contrary, were noted to increase uterine prolapse and incontinence during phase III trials that prematurely terminated. No data are available on the genitourinary effect of toremifene and on the newer SERMs currently undergoing phase III trials: basedoxifene, lasofoxifene, and arzoxifene. CONCLUSION: Contrary to their effects in bone, SERMs do not have a class-specific effect on the genitourinary tract. In fact, compounds that are more estrogenic on the uterus such as levormeloxifene and idoxifene also increase the risk of prolapse and incontinence. SERMs can adversely affect the pelvic floor and incontinence but data from urodynamic studies are not yet available. Data on prolapse are contradictory. Given the increased incidence of prolapse and incontinence observed in several licensing trials, more focused research on the effect of these molecules on pelvic floor function is needed.

[Clinical evaluation of estramustine phosphate in the treatment of patients with advanced breast cancers].

Estramustine phosphate, an anti-prostatic cancer agent, was investigated on eleven patients to evaluate the efficacy in a treatment of advanced breast cancers. The daily dose of medication was 840 mg. According to criteria of Japan Society for Cancer Therapy, none was assessed as CR, three as PR, four as NC and PD. The response rate was 27.3%. There was no differences in response rates among estrogen receptor status. A favourable response was observed in postmenopausal patients but no response in premenopausal, as well as a good response in lesions of soft tissue and lung, a poor response in lesions of liver and bone. As to toxicity of estramustine phosphate, gastrointestinal disorders such as nausea, vomiting and diarrhea were noted frequently during the treatment, and a long term administration was not able to perform in premenopausal patients because of vaginal bleeding and discharge, and pain in breast. The estramustine phosphate therapy for advanced breast cancers was regarded as one of modalities for a treatment of postmenopausal patients as a second line therapy. This is the first report in Japan discussing the efficacy of estramustine phosphate for a treatment of breast cancer.

Pseudoincontinence secondary to unopposed estrogen replacement in the surgically castrate premenopausal female.

Over a four-year period, approximately 200 patients were evaluated for incontinence at the Urogynecology Clinic of the University of Minnesota Hospitals. Seven women between the ages of 26-56 complained of incontinence beginning shortly after hysterectomy-oophorectomy for benign disease. Each gave a history of continuous leakage of urine per vagina. Urodynamics, provocative testing, and home pad tests with urinary dye all failed to prove incontinence. A common historic feature was replacement therapy with unopposed conjugated estrogen. Addition of a progestational agent to the estrogen replacement regimen eliminated the fluid loss per vagina in six of the seven women and improved it in the remaining patient. Unnecessary surgery and evaluation might have been prevented had this condition been recognized earlier.

Clinical experience with a triphasic oral contraceptive ('Trinordiol') in young women.

Seven hundred and fifty cycles of treatment with a new triphasic oral contraceptive (WL-49(50). 'Trinordiol') containing the lowest quantity of steroids of all available preparations were evaluated in 75 healthy young women (mean age 19.6 years), 70% of whom had regular, normal cycles. Sixty-five percent had not used contraception before; the others had previously been on combined or progestagen-only oral contraceptives or had an IUD. The mean length of treatment with the triphasic preparation was 10 cycles. No pregnancy was recorded during the 750 cycles of treatment. Fifteen (20%) women dropped out of the study for medical reasons, essentially breast tenderness, weight increase, spotting and nausea, in decreasing order of frequency. Mastalgia was present in 21% of the women (8.9% of the cycles) during triphasic oral contraception, but this symptom disappeared in more than half of the cases within 3 months of continued use. Other side-effects were less frequent: vaginal discharge (4.4% of the cycles), nausea (3.7%), abdominal and leg cramps (2.8%), headaches (3.2%) and weight increase (3%). Spotting and breakthrough bleeding were reported during only 1.9% of the cycles, a remarkably low frequency. No absence of withdrawal bleeding was noted. Weight and blood pressure changes were minimal and never reached statistical significance. Hypertension developed during triphasic medication in 1 predisposed individual. Complaints of oestrogen-related symptoms such as breast tenderness and digestive disorders were probably due to the reduced progestagen content of the preparation compared with combined low fixed daily dose oral contraceptives. However, no increases in dysmenorrhoea and/or premenstrual tension were noted. It is concluded that the triphasic preparation provides effective contraception with excellent cycle control and minimal side-effects, which should help to increase the acceptability of low-dose combined oral contraceptives.

PIP: 750 cycles of treatment with a new triphasic oral contraceptive (OC), (WL-49(50), Trinordiol), containing the lowest quantity of steroids of all available preparations were evaluated in 75 healthy young women (mean age 19.6 years). 70% of all young women had normal, regular menstrual cycles. 65% had not used contraception previously, and the others had previously taken combined or progestogen only OCs or had an IUD. The mean length of treatment with the triphasic preparation was 10 cycles. Routine clinical evaluation, including gynecological examination, weight and blood pressure measurement, assessment of cycle events, and recording of spontaneously reported side effects, was performed every 3 months. Cycle control during triphasic OC use was very good. There was a statistically significant trend of the cycles toward more regularity than prior to this type of contraception, with an increased frequency of 28-day cycles. Duration of menses was significantly reduced and menstrual volume was more frequently rated by the women as normal. Spotting and breakthrough bleeding showed a very low frequency, the latter accounting for less than 10% of intermenstrual bleeding during triphasic OC medication. Frequency of side effects was 53.3% (40 women) during triphasic OC use. 20% of the population reported side effects among the reasons for stopping triphasic OC use. Breast tenderness was the most frequent side effect recorded in almost 9% of the total number of treatment cycles. It affected 21% of the women under study, a significantly more frequent occurrence than before triphasic OC use in these individuals. The tendency of this symptom to improve was observed in more than half of the cases within 3 months use of triphasic OC use. Other signs of estrogenic dominance such as gastrointestinal disturbances, vaginal discharge, pelvic congestion, and leg cramps were also present but much less prominent than breast tenderness. 16 (21.3%) patients presented with breast tenderness for 67 (8.9%) cycles. Nausea and vomiting were experienced by 6 (8%) patients for 28 (3.7%) cycles. Vaginal discharge was present in 10 (13.3%) patients for 33 (4.4% cycles). Spotting and breakthrough bleeding occurred in 6 (8%) women for 14 (1.9% cycles). Absence of change in weight was recorded in 1/3 of the women studied; another 1/3 experienced a weight reduction of 1-4 kg and the last 1/3 gained 1-4 kg. There were no statistically significant variations in either systolic or diastolic blood pressure values.

Side effects of oral contraceptives.

PIP: It is estimated that 10-15 million women use oral contraceptives in the U.S. The 2 types of pills available are combination products containing both an estrogen and progestin, and single entity products with only progestin. Although more side effects are associated with estrogen, combination pills are the preferred prescription. Most often side effects are mild and disappear after continued use or switching to another type of pill. Some of the side effects are nausea; weight gain; chloasma; cervical extrophia and leukorrhea; hypermenorrhea; spotting and breakthrough bleeding; galactorrhea and pituitary tumors; choreiform movement disorder; endometrial cancer; and, hepatic effects. Fetal exposure to exogenous estrogens and progestins has been reported to result in increased risk for the heart and neural tube defects. Teratogenic effects subsequent to discontinuation of OCs does not appear to be a risk. The beneficial side effects of oral contraceptives are that the incidence of menorrhagia, benign breast neoplasm, dysmenorrhea, iron-deficiency anemia, premenstrual tension, acne, and ovarian cysts are lower in OC users. Thryoid diseases may be reduced by OCs.^ieng

Ethynodiol diacetate as a contraceptive.

PIP: 437 multiparous women were given ethynodiol diacetate in continuous microdoses of .35 mg/day, .50 mg/day, .25 mg/twice a day, or .125 mg/twi ce a day. 7 pregnancies occurred during treatment, 5 due to medication failure; 2 were in the .5 mg/day group and 3 were in the .125 mg/twice a day group. Women taking .5 mg/day and .25 mg/twice a day had most menstrual irregularities (10% of the cycles). Side effects noted were: headache, nervousness, nausea and vomiting, and abdominal pain. Most of the patients lost weight; lactation did not appear to be affected by the medication. Uterine tone changed during treatment; there was a decrease in frequency, an increase in intensity and an increase in the tone of the contractions. It is concluded that the contraceptive efficacy was directly related to dosage as were menstrual and uterin disturbances, except for side effects. Ovulation was not inhibited although contraception was produced.^ieng

[Clinical study of a new, normophasic type oral contraceptive]. / Etude clinique d'un nouveau contraceptif oral de type normophasique.

PIP: A new "normophasic" oral contraceptive, Fisioquens (7 tablets of .05 mg ethinylestradiol, and 15 tablets with .05 mg ethinylestradiol and 1 mg lynestrenol) was taken by 120 fertile women for an average of 9.24 cycles, maximum of 12 cycles, and a total of 1108 cycles. There were no pregnancies, no drug related drop outs, good menstrual control and very few side effects. Latent period before withdrawal bleeding was 2-3 days in 89.9% of cycles. Bleeding lasted 4.5 days in 72% of cycles, occurred every 28 days in 88%, was usually the same in amount, sometimes increased. There was breakthrough bleeding in .38% of cycles, spotting in 2%, and amenorrhea in only 2 cycles. Side effects included nausea (worsened in 3.3%, improved in 5%); headache (worsened in 9.1%, improved in 10.8%); breast pain (worsened in 7.5%, improved in 17.5%); leg pain (worsened in 8.3%, improved in 7.5%); leucorrhea (worsened in 1.6%, improved in 30.8%); psychological status (worsened in 2.4%, improved in 7.5%). Whether the patients had previously been taking other pills was not stated. The author concluded that this formulation was efficacious and acceptable because it resembles a sequential, but gives longer protection of progestagen.^ieng

Low dosage megestrol acetate application as contraceptive.

PIP: A review of the development of low dose progesterone is presented. Continuous low-dose megestrol acetate therapy data from 43 patients is presented. When short cycle lengths, breakthrough bleeding, and amenorrhea occurred, a lower dose of megestrol acetate was substitute. 78% of the cycles varied between 21 and 38 days a breakthrough bleeding occurred in 19.6% cycles, and average flow was 5.2 days. There were no breakthrough pregnancies in this group. A majority of the cycles with megestrol acetate were ovulatory, but the cervical mucus was hostile and vaginal smears showed a definite progestational effect.^ieng