Hemostatic effects of two desogestrel-containing combined oral contraceptive regimens: a multinational, multicenter, randomized, open-label study.

PURPOSE OF INVESTIGATION: To compare the effects of desogestrel (DSG) 150 mcg/ethinyl estradiol (EE) 20 mcg for 21 days followed by either seven days of EE ten mcg (21/7-active) or no treatment (DSG/EE+no Tx) on hemostatic markers. MATERIALS AND METHODS: This was a randomized, multicenter, open-label study that enrolled healthy premenopausal women. Non-inferiority of 21/7-active to DSG/EE+no Tx was determined if the upper limit of the two-sided 95% CI of the mean treatment difference in prothrombin fragment 1+2 (F1+2) over 24 weeks between groups was < 130 pmol/L. RESULTS: 246 subjects (n = 125, 21/7-active; n = 121, DSG/EE+no Tx) comprised the primary analysis. Mean F1+2 levels increased in both 21/7-active and DSG/EE+no Tx regimens (least square [LS] mean changes +45 pmol/L and +56.8 pmol/L, respectively). LS mean treatment difference was -11.8 pmol/L (95% CI: -54.8, 31.2). CONCLUSION: The effect of adding EE ten mcg to the seven-day hormone-free interval of DSG/EE on F1+2 levels was non-inferior to traditional DSG/EE.

Continuous versus cyclic use of oral contraceptives after surgery for symptomatic endometriosis: a prospective cohort study.

OBJECTIVE: To evaluate the efficacy of continuous oral contraceptive (OC) use versus the usual cyclic fashion in the recurrence of endometriosis-related symptoms after surgery. DESIGN: Prospective cohort trial involving patients in two tertiary care units. SETTING: Academic institution in collaboration with a private hospital. PATIENT(S): 356 patients underwent surgical treatment by laparoscopy for symptomatic endometriosis. INTERVENTION(S): After surgical treatment for endometriosis, patients offered 6-month course of cyclic OC (including a 7-day pill-free period) or continuous OC. MAIN OUTCOME MEASURE(S): Recurrence rate of endometriosis-related symptoms and endometriomas after fertility-sparing surgery. RESULT(S): Out of 356 patients, 167 were placed on the usual cyclic OC course and 85 on continuous OC for a minimum of 6 months. The continuous OC group experienced a statistically significant reduction in recurrence rates for endometrioma, dysmenorrhea, and non-menstrual pelvic pain as compared with the cyclic OC group. There was no reduction in the recurrence of dyspareunia between the two groups. CONCLUSION(S): After surgical treatment of endometriosis, the use of both cyclic and continuous OC improves pain symptoms when compared with preoperative scores. Continuous OC appears to be associated with a reduced recurrence rate for dysmenorrhea, non-menstrual pelvic pain, and endometrioma but not for dyspareunia as compared with cyclic OC.

Types of combined oral contraceptives used by US women.

BACKGROUND: We sought to estimate the prevalence of types of combined oral contraceptives (COCs) used among US women. STUDY DESIGN: We analyzed interview-collected data from 12,279 women aged 15-44 years participating in the National Survey of Family Growth, 2006-2010. Analyses focused on COC use overall, by pill type, across sociodemographics and health factors. RESULTS: The prevalence of current COC use (88 different brands) was 17%. The majority of COC users used earlier-formulation COCs: ≥30 mcg (67%) versus <30 mcg estrogen (33%), monophasic (67%) versus multiphasic (33%) dosages and traditional 21/7 (88%) versus extended/other cycle regimens (12%) regimens. Norgestimate (32%) and norethindrone (20%) were the most commonly used progestins. Sociodemographic, gynecological and health risk factors were associated with type of COC use. CONCLUSION: Further investigation of specific COC use and of the factors associated with types of pills used among US women at the population level is needed.

Long-term cyclic and continuous oral contraceptive therapy and endometrioma recurrence: a randomized controlled trial.

OBJECTIVE: To evaluate long-term cyclic and continuous administration of oral contraceptive pills (OCP) in preventing ovarian endometrioma recurrence after laparoscopic cystectomy. DESIGN: Prospective, randomized, controlled trial. SETTING: Tertiary care University Hospital. PATIENT(S): Two hundred thirty-nine women who underwent laparoscopic excision of ovarian endometriomas. INTERVENTION(S): Patients were divided randomly into three groups: nonusers receiving no therapy and cyclic and continuous users receiving low-dose, monophasic OCP for 24 months in cyclic or continuous administration, respectively. MAIN OUTCOME MEASURE(S): Endometrioma recurrence, size of recurrent endometrioma, and growth rate during at least 2 years follow-up evaluated by transvaginal ultrasonography. RESULT(S): The crude recurrence rate within 24 months was significantly lower in cyclic (14.7%) and continuous users (8.2%) compared with nonusers (29%). The recurrence-free survival was significantly lower in nonusers compared with cyclic and continuous users. The mean recurrent endometrioma diameter at first observation was significantly lower in cyclic (2.17 +/- 0.45 cm) and continuous users (1.71 +/- 0.19 cm) compared with nonusers (2.73 +/- 0.56 cm). The mean diameter increase every 6 months of follow-up was significantly reduced in cyclic users (0.31 +/- 0.18 cm) and continuous users (0.25 +/- 0.09 cm) versus nonusers (0.48 +/- 0.3 cm). No significant differences between cyclic users and continuous users in terms of endometrioma recurrence were demonstrated. CONCLUSION(S): Long-term cyclic and continuous postoperative use of OCP can effectively reduce and delay endometrioma recurrence.

Efficacy and safety of a 28-day oral contraceptive with 7 days of low-dose estrogen in place of placebo.

BACKGROUND: The study was conducted to evaluate the efficacy and safety for the prevention of pregnancy of a 28-day oral contraceptive (OC) containing 150 mcg desogestrel (DSG)/20 mcg ethinyl estradiol (EE) for 21 days followed by 7 days of 10 mcg EE (Cette-28). STUDY DESIGN: A 6-month, prospective, multicenter, single-arm study was conducted in 1302 women aged 18-45 years. RESULTS: Over six cycles of treatment, the cumulative risk of pregnancy among all treated subjects (n=1262) was 0.9%. The Pearl Index for women 18-35 years of age (n=1042) was 2.20, including 9 pregnancies with estimated conception dates during active drug ingestion or up to 7 days after the last combination tablet. The rate of unscheduled bleeding was low and the duration of scheduled bleeding was approximately 2 days during each of the six treatment cycles. The safety profile was similar to what has been reported for other OCs. CONCLUSION: This low-dose, 28-day OC incorporating 7 days of 10 mcg EE during the hormone free interval is effective and safe for the prevention of pregnancy and is well-tolerated by women.

[The influence of sequential hormonal therapy on biochemical and cardiovascular indices in menopause]. / Utjecaj sekvencijske hormonske terapije na biohemijske i kardiovaskularne pokazatelje u menopauzi.

This study follows 94 patients, age 45 to 60, by controlled, random and prospective studies in time period of six months. Out of total number of patients, 53 were divided into research group and treated with hormonal therapy (2 mg of estradiol and 0,5 mg of norgestrel), 41 patients were divided into control group and treated with refemin (Cimicifuga recemosa). Results were statistically processed using Student test and ANOVA, giving us following results: use of HNL resulted with statistically significant changes--increase of heart frequency (*p<0,01), QTc-intervals (**p=0,01), increase of systolic pressure (**p=0,01), increase of diastolic pressure (**p=0,01), increase of body mass index (**p=0,01), endometrial thickness decrease (**p=0,01); use of Cimicifuge recemose resulted with statistically significant changes--increase of diastolic pressure(*p=0,01), increase of body mass index (BMI) (*p=0,01) and endometrial thickness decrease (*p=0,05). By testing research and controlled group with ANOVA test, we have determined that there is statistical difference in operating between recovered hormone therapy and Cimicifuge recemose within parameters of hearth frequency and diastolic pressure.

[Advances in hormonal contraception]. / Adelantos en anticoncepción hormonal.

This review provides an update regarding newer options in hormonal contraception that include the progestin-releasing intrauterine system, the contraceptive patch and ring, the single rod progestin-releasing implant, extended and emergency oral contraception and recent advances in hormonal male contraception. These methods represent a major advancement in this field, allowing for the development of more acceptable, safety and effective birth control regimens.

The use of triphasic oral contraceptives in a continuous use regimen.

OBJECTIVE: The objective of this study was to describe the characteristics of and outcomes and side effects in patients using triphasic oral contraceptives (OCs) in a continuous use regimen. METHODS: A retrospective review of patient charts from four community-based physician practices was conducted. All patients had been using triphasic OCs in a continuous regimen (i.e., to prevent withdrawal bleeding) for a planned duration of at least three 28-day cycles. Data collected through retrospective chart abstraction included demographic and clinical indicators, duration of and reason for continuous triphasic OC use, prior OC history and side effect incidence and treatment. RESULTS: Forty-three patients meeting the inclusion criteria had data of sufficient quality to be included in all analyses. These patients represented 603 total cycles. Nearly half of the patients (49%) indicated that their primary reason for continuous OC use was personal preference rather than medical reasons. More than half of the patients (56%) had previously used triphasic OCs in a noncontinuous regimen; 24% had no prior OC experience. The median duration of continuous use was 237 days (including right-censored patients; range, 55-994). Of the 39% of patients who terminated continuous use, the most common reason given was the desire to become pregnant (35%). Sixty-one percent of the patients reported no side effects from continuous use. The most common side effect occurring beyond Day 21 of continuous use was breakthrough bleeding (reported in four patients). Survival analysis indicated that time on continuous triphasic use was positively related to parity >0 (p<.05) and the absence of side effects (p<.1). CONCLUSION: The data suggest that successful continuous use is feasible with triphasic OCs, with few adverse side effects.

Oral contraceptives and libido in women.

Oral contraceptives (OCs) provide safe, effective, and reversible contraception and are widely used by women for fertility control. Little is known about the effects of OCs on sexual functioning. This paper critically examines the published literature addressing the impact of OCs on sexual desire or libido. We reviewed 30 original research studies. In the retrospective, uncontrolled studies (n = 17), it was found that most women reported an increase in libido during OC use. In the uncontrolled, prospective studies (n = 4), it was found that most women reported little change in libido during OC use. In the prospective and cross-sectional controlled studies (n = 4), women using OCs reported both increased and decreased libido compared to non-OC users. The findings from randomized, placebo-controlled studies (n = 5) were mixed: In the most recent and well-conducted trial, a decrease in libido in OC users compared to placebo users was found. Overall, women experience positive effects, negative effects, as well as no effect on libido during OC use. Better-designed studies are needed to establish the independent, causal effects of OCs on libido.

"Estrophasic" dosing: A new concept in oral contraceptive therapy.

The first of a new "estrophasic" type of oral contraceptive with 20 microg ethinyl estradiol on cycle days 1 through 5, 30 microg ethinyl estradiol on days 6 through 12, and 35 microg ethinyl estradiol on days 13 through 21 and 1 mg norethindrone acetate throughout the cycle (Estrostep; Parke-Davis, Morris Plains, NJ) combines a continuous low progestin dose with a low, gradually increasing estrogen dose. It was developed to ensure good cycle control while conferring the benefits of low hormone content, such as minimizing estrogen-related side effects. In a double-blind, randomized, parallel-group trial, Estrostep provided acceptable cycle control and excellent tolerableness, comparable to that of the 30-microg ethinyl estradiol monophasic control drug. In a second study Estrostep demonstrated a neutral impact on serum lipids, like the triphasic control drug. This new oral contraceptive design offers a useful low-dose alternative to existing combination preparations.

[Biological and clinical safety of nomegestrol acetate administered alone then associated in inverse sequence with transdermal 17 beta estradiol, in women at risk of dyslipoproteinemia type IIa]. / Tolérance biologique et clinique du Nomégestrol acétate, administré seul puis associé en séquentiel inversé au 17 beta estradiol cutané, chez des femmes à risque présentant une dyslipoprotéinémie de type IIa.

In this study including 26 patients with dyslipoproteinemia classified IIa, we evaluated biochemical and clinical safety of Nomegestrol acetate (Lutenyl) used for its antigonadotrophin property. It was administered alone, during 3 cycles at the dose of 5 mg/d for 21 days by cycle and then it was associated (at the same sequence and dose), without any wash out, for the next 6 cycles, with a 17 beta estradiol patch (Estraderm TTS 50), 50 micrograms/d from the 11th to the 21st day of each cycle. Nomegestrol acetate, alone, had no significant effect on glycemia, antithrombin III, triglycerides, total cholesterol, apoprotein A1, and LpA1 values compared to those at baseline but apoprotein B and Lp (a) values tended to decrease slightly. Serum progesterone levels were collapsed, and FSH values were low. Weight and blood pressure remained constant. Adding 17 beta estradiol enabled to significantly decrease and normalize the apoprotein B values after the first 3 cycles compared to the baseline values, then these values remained constant during the next 3 cycles. There was no effect on the other parameters (except for a significant increase in plasmatic estradiol values) on the antigonadotrophin property of Nomegestrol acetate, nor on weight and blood pressure which remained constant. Moreover, we observed an important decrease in the rate of amenorrheic cycles compared to those with Nomegestrol acetate alone.

[Mesenteric vein thrombosis with hemorrhagic infarct of the small intestinal as a complication of oral contraceptives]. / Mesenterialvenenthrombose mit hämorrhagischem Dünndarminfarkt als Komplikation oraler Contraceptiva.

Venous thrombosis is a documented complication of oral contraceptives in adolescents and young women. The frequency of thrombosis increases in presence of additional risk factors as e.g. smoking and obesity. This is a case-report of a mesenterial vein thrombosis in a 24 years old woman on low estrogen dose triphasic oral contraceptives combined with smoking and obesity. Wide jejunal haemorrhagic infarction with acute abdomen and volume deficiency shock conducted to diagnosis finally by emergency laparotomy. Wide resection of jejune was required.

The relationship between mood and sexuality in women using an oral contraceptive as a treatment for premenstrual symptoms.

This study investigated the effects of a triphasic oral contraceptive (OC) on mood and on sexual interest in a group of 45 women with premenstrual complaints. Subjects made daily ratings of mood and sexual interest for one baseline cycle and were then randomly assigned to receive either placebo or OC for 3 mo. Women who received the OC reported decreased sexual interest during the menstrual and postmenstrual phases of the cycle. The predominant effect of both the OC and the placebo on mood was one of improvement, particularly during the premenstrual phase. There was little evidence of co-variation of mood and sexual interest in either group. Although the mechanism for the adverse effects of the OC on levels of sexual interest in unknown, it is clear that this effect was not simply a consequence of pill-induced negative mood change. The findings provide evidence that mood and sexual desire are dissociable and suggest that OCs can have direct effects on women's sexuality.

PIP: In Montreal, Canada, after 45 women who were seeking treatment for self-reported moderate to severe premenstrual changes made daily ratings of mood and sexual interest for 1 baseline cycle, they were blindly allocated to a group receiving a triphasic oral contraceptive (OC) Synphasic for 3 months or a group receiving a placebo for 3 months. Researchers wanted to determine the effects of the OC on mood and on sexual interest. Ratings of depression and sexual interest in both groups demonstrated significant cyclicity. For example, depression scores were highest during the premenstrual phase and lowest during the postmenstrual phase. Sexual interest peaked in the postmenstrual phase and bottomed out in the premenstrual phase. Both groups experienced a loss of cyclicity for mood and sexual interest by the 3rd treatment cycle. During the premenstrual phase, depression scores fell significantly in both groups (p .01), but an increase in sexual interest did not occur. During the menstrual phase, the OC group experienced a considerable drop in sexual interest (p .01), but the mood did not change. On the other hand, postmenstrually, the mood worsened, not significantly however, among the OC users, coinciding with a significant reduction in sexual interest (p .01). Yet mood and sexual interest were not correlated. In fact, covariation of mood and sexual interest basically did not occur in either group. Generally, both the OC and the placebo improved the mood, especially during the premenstrual phase. The negative effect of the OC on sexual interest was not just a result of OC induced negative mood change. These results show that mood and sexual desire are not linked. They intimate that OCs directly influence women's sexuality.

The impact of oral contraceptives on the experience of perimenstrual mood, clumsiness, food craving and other symptoms.

Two-hundred and seventy-six oral contraceptive (o.c.) users (171 combine o.c. and 105 triphasic o.c.) were compared with 276 non-o.c. users. All women regarded themselves as PMS sufferers, and the groups were matched for age, parity and marital status. Each woman rated severity of 27 symptoms during the premenstrual, menstrual and postmenstrual phases of their last menstrual cycle. The o.c. users reported significantly less menstrual pain and premenstrual breast tenderness. When controlling for the severity of premenstrual depression, there were no differences between the three groups in the timing or severity of perimenstrual food craving or clumsiness. When controlling for the severity of menstrual pain, the o.c. users showed significantly less improvement in negative mood during the menstrual phase, compared with non-users. The apparent tendency for o.c. users to show either a delayed or more prolonged pattern of perimenstrual negative mood deserves further study.

Effect of "missed" pills on oral contraceptive effectiveness.

OBJECTIVE: The purpose of this study was to determine whether missing pills in an oral contraceptive (OC) cycle resulted in folliculogenesis and eventual ovulation. METHODS: Fifteen women selected from a population requesting tubal reanastomosis were randomized into three groups and issued pill packs missing four consecutive pills in specific sequences, as follows: group I, days 1-4; group II, days 3-6; and group III, days 6-9. Serum was drawn for assay of LH, FSH, estradiol (E2), and progesterone, and serial ovarian ultrasound examinations were done to study follicular development throughout the cycle at 4-day intervals. RESULTS: No subject ovulated, as suggested by serum progesterone concentrations (not exceeding 0.63 ng/mL for any woman) and ultrasound assessment of follicular development (no follicular diameter exceeding 13 mm). The highest (mean +/- standard deviation) serum concentrations of LH and FSH in any group (13.25 +/- 18.71 and 14.40 +/- 7.71 mIU/mL, respectively) and of E2 (44.35 +/- 26.79 pg/mL) were observed during or immediately after the pill-free interval. Ovarian ultrasound examinations suggested suppressed folliculogenesis in all groups. No functional ovarian cysts were detected. CONCLUSIONS: Oral contraceptives exerted a similar degree of pituitary and ovarian suppression even when the subjects missed four pills at varying times in a cycle. The anovulatory effect persisted when the OC pills were reinstituted and taken reliably after an interval of noncompliance.

A prospective treatment study of premenstrual symptoms using a triphasic oral contraceptive.

Eighty-two women with complaints of moderate to severe premenstrual symptoms were recruited for a double-blind, controlled trial of a triphasic oral contraceptive (o.c.). Subjects made daily ratings of symptoms for at least one baseline cycle and were then randomly assigned to receive either placebo or o.c. for three months. Twenty-three women dropped out of the study (18 o.c., 5 placebo), 13 failed to show prospective confirmation of moderate to severe premenstrual symptoms, and one placebo subject had an anovulatory cycle. Forty-five women with prospectively-confirmed premenstrual changes (20 o.c., 25 placebo) completed the study. Premenstrual breast pain and bloating were significantly reduced with active treatment compared to placebo (p less than 0.03) but there were no beneficial effects of the o.c. over placebo for any of the mood symptoms. Women who received o.c.s reported decreased sexual interest after starting treatment and this effect was independent of any adverse influence on mood.

PIP: A placebo-controlled, double-blind study of triphasic oral contraceptives for prospectively confirmed premenstrual syndrome (PMS) was conducted with 82 subjects, 59 of whom completed the study and who were later confirmed to have moderate to severe premenstrual symptoms. 212 subjects were recruited between April 1987 - June 1988, and completed a menstrual history form and a 95-item retrospective questionnaire on premenstrual symptoms. Subjects took Synphasic (Syntex, Mississauga, Canada) containing 35 mcg ethinyl estradiol and 0.5 mg, 1.0 mg, and 0.5 mg norethindrone. Subjects were monitored for 1 menstrual cycle for baseline, then took triphasic or placebo for 3 cycles. 23 oral contraceptive taking and 36 placebo subjects completed the trial: completers had higher status occupations and lower symptom severity scores than dropouts. Both pill and placebo groups showed significant clinical improvement on every symptom except headache. Symptom scores decreased significantly between baseline and 3rd treatment cycle, and between menstrual phase scores and the variables "mood swings," "more sleep," "unhappy," and "tense" in the 2nd treatment cycle compared with the 1st treatment cycle in both groups. In the pill group ratings of premenstrual breast pain were significantly lower in the 3rd treatment cycle compared with baseline (p0.05), and to the 1st treatment cycle (p0.01). No significant changes in breast pain were found in the placebo group. Some pill cycles showed significant reduction in edema. Those in the pill group who were initially rated as "depressed" showed greater improvement in work impairment, sleep requirements, and energy level premenstrually. The pill group, however, reported significantly lower sexual interest during treatment. This is the 1st reported double-blind, placebo-controlled, prospectively confirmed study of oral contraceptives for PMS.

[Response to the letter by Prof. Kuhl: "Does a rise in endogenous estradiol during treatment with low-dose ovulation inhibitor signify increased risk"?]. / Erwiderung zum Leserbrief von Herrn Prof. Kuhl: "Bedeutet ein Anstieg des endogenen Oestradiols während der Behandlung mit niedrig dosiertem Ovulationshemmer (OH) ein erhöhtes Risiko"?

PIP: During testing new sequential preparations such as Trinordiol the weak suppression of gonadotropin and the partly increased endogenous estradiol (E2) and also partly increased progesterone were noted in the course of 30,000 checkups by contraceptive users when clinical symptoms were confirmed by ultrasound and biochemical analysis. In micropill users these were acute abdominal and breast pain, often follicular ripening in the ovaries, and cysts in the ovaries and in the breast with increased E2 values up to ovulatory values in some. The strong pain in the lower abdomen required intervention. It has been known that ethinyl estradiol (EE) and gestagens inhibit ovulation. In a study of 7 patients taking 40 mcg of gestoden there were 6 cases of ovulation inhibition (4 times along with follicular ripening) and 1 case of corpus luteum insufficiency. There were 2 instances of follicular ripening in 32 patients using Femovan containing 30 mcg of EE with 75 mcg of gestoden. With a 20 mcg preparation these signs occurred repeatedly when young girls complained of strong breast pain and breast enlargement. Shifting to a preparation containing 30 mcg of EE with the same dose of gestagen eliminated the complaints. This contradicts the hypothesis that all receptors are occupied by Ee and that endogenous E2 production cannot exercise its effect. Therefore, development of micropills with a somewhat higher gestagen dose has been suggested. There are patients whose cycle regulation is aided only by sequential preparations with 50 mcg of EE. It is concluded that ovulation inhibition is dependent on the dose and structure of gestagens, with the resorption and current metabolism of steroids in agreement with individually differing suppression of the ovaries.^ieng