Increased serum levels of nitric oxide metabolites among users of levonorgestrel-releasing implants [corrected] a possible role in progestin-induced bleeding.
(41/142)
BACKGROUND: Nitric oxide (NO) is a potent angiogenic and vasodilator factor that could be involved in progestin-induced bleeding. This study aimed to assess possible changes in the serum levels of NO metabolites in users of levonorgestrel-releasing implants (LNG-implants) [corrected] and to identify any correlation between some of their clinical characteristics and NO metabolite levels. METHODS: This cross-sectional study included 37 LNG-implants [corrected] users; a single 5 ml venous blood was collected at different periods of [corrected] use. Women were divided into users with acceptable menstrual bleeding (n 5 13) [corrected] and those having abnormal bleeding patterns (n 5 24) [corrected] The controls are 13 age-matched healthy women; they were fertile, had regular menstruation and did not use any contraceptive method in the previous 3 months. NO was determined by the evaluation of its oxidation products (nitrites and nitrates) where the nitrates were reduced to nitrites with cadmium filings; total serum concentrations of nitrites were measured by using the Griess reaction. RESULTS: The mean serum levels of NO metabolites were significantly higher in the LNG-implants [corrected] users than in the controls (mean+/-SE) 34.9+/-11.3 versus 6.1+/-1.5 mumol/l (P<0.001) [corrected] The mean serum levels of NO metabolites were significantly higher in the LNG-implants [corrected] users with abnormal bleeding patterns than in those with normal bleeding patterns (mean+/-SE) 41.3+/-7.4 versus 23.2+/-5.8 mumol/l (P<0.001) [corrected] There was a positive correlation between NO levels and both prolonged spotting and heavy/prolonged bleeding days (P<0.001 and P<0.01, respectively) and negative correlation between NO levels with the duration of use and length of the menstrual cycle (P<0.05). CONCLUSION: The significantly increased serum levels of NO metabolites among LNG-implants [corrected] users may primarily reflect an increase in its endometrial production, possibly secondary to its increased liberation by systemic vascular endothelium. This may result in enhanced endometrial angiogenesis and vascular dilatation which can induce and perpetuate abnormal excessive/prolonged uterine bleeding. (+info)
Superior cycle control with a contraceptive vaginal ring compared with an oral contraceptive containing 30 microg ethinylestradiol and 150 microg levonorgestrel: a randomized trial.
(42/142)
BACKGROUND: This trial was conducted to compare cycle control with vaginal ring a combined contraceptive vaginal ring, and a combined oral contraceptive (COC) delivering 30 mug ethinylestradiol (EE) and 150 mug levonorgestrel. METHODS: This open-label, randomized, multi-centre, Phase III study involved adult women from 11 countries. Subjects were treated with either vaginal ring or a COC for 13 cycles (12 months). RESULTS: A total of 1030 subjects (vaginal ring, n=512; COC, n=518) comprised the intention-to-treat (ITT) population. The percentage of women in the ITT population who completed the trial was 70.9% for vaginal ring and 71.2% for the COC group. The incidence of breakthrough bleeding and spotting over cycles 2-13, the primary efficacy parameter, was lower with vaginal ring (range 2.0-6.4%) than the COC (range 3.5-12.6%), and for cycles 2 and 9 the lower incidence with vaginal ring was confirmed as statistically significant (P=0.003 and P=0.002 respectively). The incidence of intended bleeding was significantly higher over all cycles with vaginal ring (58.8-72.8%) than with the COC (43.4-57.9%). CONCLUSIONS: Cycle control with vaginal ring was excellent and superior to that of a COC containing 30 mug EE. (+info)
Heat acclimation and physical training adaptations of young women using different contraceptive hormones.
(43/142)
Although endogenous and exogenous steroid hormones affect numerous physiological processes, the interactions of reproductive hormones, chronic exercise training, and heat acclimation are unknown. This investigation evaluated the responses and adaptations of 36 inactive females [age 21 +/- 3 (SD) yr] as they undertook a 7- to 8-wk program [heat acclimation and physical training (HAPT)] of indoor heat acclimation (90 min/day, 3 days/wk) and outdoor physical training (3 days/wk) while using either an oral estradiol-progestin contraceptive (ORAL, n = 15), a contraceptive injection of depot medroxyprogesterone acetate (DEPO, n = 7), or no contraceptive (EU-OV, n = 14; control). Standardized physical fitness and exercise-heat tolerance tests (36.5 degrees C, 37% relative humidity), administered before and after HAPT, demonstrated that the three subject groups successfully (P < 0.05) acclimated to heat (i.e., rectal temperature, heart rate) and improved muscular endurance (i.e., sit-ups, push-ups, 4.6-km run time) and body composition characteristics. The stress of HAPT did not disrupt the menstrual cycle length/phase characteristics, ovulation, or plasma hormone concentrations of EU-OV. No between-group differences (P > 0.05) existed for rectal and skin temperatures or metabolic, cardiorespiratory, muscular endurance, or body composition variables. A significant difference post-HAPT in the onset temperature of local sweating, ORAL (37.2 +/- 0.4 degrees C) vs. DEPO (37.7 +/- 0.2 degrees C), suggested that steroid hormones influenced this adaptation. In summary, virtually all adaptations of ORAL and DEPO were similar to EU-OV, suggesting that exogenous reproductive hormones neither enhanced nor impaired the ability of women to complete 7-8 wk of strenuous physical training and heat acclimation. (+info)
Treatment of pelvic endometriosis with etonogestrel subdermal implant (Implanon).
(44/142)
BACKGROUND: Endometriosis is one of the commonest benign gynaecological disorders and has a peak incidence between 30 and 45 years of age. Treatment options are medical or surgical, depending on the location and extent of the disease and the woman's childbearing aspirations or need for contraception. Over the past five decades several formulations of progestogen have been used to treat endometriosis. METHODS: Our study was not planned research but a series of case studies of women with severe symptoms of endometriosis treated in an innovative way with a new long-acting progestogen contraceptive system (etonogestrel subdermal implant) which could reasonably have been expected to have a favourable effect on their disease and its symptoms. RESULTS: Five women with severe pelvic endometriosis were treated. Two of them were nulliparous and wished to become pregnant in due course; the other three had completed their childbearing and were contemplating hysterectomy. One of the five women had relief of pelvic pain but requested removal of the implant after 3 months because of side effects; the other four remained very satisfied with their treatment for the symptoms of pelvic endometriosis. Two of the four very satisfied women have had their implant replaced and the other two are expected to have their implant replaced when necessary. CONCLUSION: Etonogestrel subdermal implants are an additional treatment option in women with symptoms related to pelvic endometriosis. (+info)
Migration of implanon: two case reports.
(45/142)
These two case reports describe migration of Implanon (the single-rod contraceptive implant). A review of the literature revealed true migration of Implanon to be rare. A change of practice locally is described. (+info)
The role of CYP2C and CYP3A in the disposition of 3-keto-desogestrel after administration of desogestrel.
(46/142)
AIMS: Our objective was to study in vivo the role of CYP2C and CYP3A4 in the disposition of 3-keto-desogestrel after administration of desogestrel, by using the selective inhibitors fluconazole (CYP2C) and itraconazole (CYP3A4). METHODS: This study had a three-way crossover design and included 12 healthy females, the data from 11 of whom were analyzed. In the first (control) phase all subjects received a single 150 microg oral dose of desogestrel alone. In the second and third phases subjects received a 4 day pretreatment with either 200 mg fluconazole or 200 mg itraconazole once daily in a randomized balanced order. Desogestrel was given 1 h after the last dose of the CYP inhibitor. Plasma 3-keto-desogestrel concentrations were determined for up to 72 h post dose. RESULTS: Pretreatment with itraconazole for 4 days significantly increased the area under the plasma concentration-time curve (AUC) of 3-keto-desogestrel by 72.4% (95% confidence interval on the difference 12%, 133%; P = 0.024) compared with the control phase, whereas fluconazole pretreatment had no significant effect (95% CI on the difference -42%, 34%). Neither enzyme inhibitor affected significantly the maximum concentration (95% CI on the difference 14%, 124% for itraconazole and -23%, 40% for fluconazole) or elimination half-life (95% CI on the difference -42%, 120% for itraconazole and -24%, 61% for fluconazole) of 3-keto-desogestrel. CONCLUSIONS: According to the present study, the biotransformation of desogestrel to 3-keto-desogestrel did not appear to be mediated by CYP2C9 and CYP2C19 as suggested earlier. However, the further metabolism of 3-keto-desogestrel seems to be catalyzed by CYP3A4. (+info)
Interaction of progestins with the human multidrug resistance-associated protein 2 (MRP2).
(47/142)
Progestins are widely used as oral contraceptives and hormone replacement therapy. Recently it has been demonstrated that many progestins are inhibitors of P-glycoprotein, possibly explaining gender differences in drug actions. In vitro evidence suggested that at least norgestimate might also inhibit other transporters like the multidrug resistance-associated protein 2 (MRP2). We therefore investigated whether norgestimate, desogestrel, medroxyprogesterone acetate, norethisterone, progesterone, cyproterone acetate, chlormadinone acetate, and levonorgestrel inhibit MRP2 in vitro using confocal laser scanning microscopy and 5-chloromethylfluorescein diacetate as a prodrug of the fluorescent 5-chloromethylfluorescein (CMF), which is actively transported by MRP2 as glutathione conjugate. Of the progestins tested, only norgestimate (50 microM) and progesterone (100 microM) significantly increased intracellular CMF fluorescence by 62% and 53%, respectively. In conclusion, the progestins norgestimate and progesterone significantly inhibit the transport activity of MRP2 in vitro. (+info)
Estradiol supplementation modulates neuroendocrine response to M-chlorophenylpiperazine in menstrual status migrainosus triggered by oral contraception-free interval.
(48/142)
BACKGROUND: Migraine triggered by oral contraception (OC)-free interval is very common and may be extremely severe, long-lasting and poorly responsive to analgesics (status migrainosus). The serotoninergic (5-HT) system is crucially involved in pain threshold and it is sensitive to estradiol (E2). Therefore, we aimed to assess neuroendocrine correlates of OC status migrainosus in response to the direct central 5-HT agonist meta-chlorophenylpiperazine (m-CPP) and to test the effect of transdermal E2 supplementation of the OC-free interval. METHODS: Clinical investigative protocol, single-blinded placebo-controlled treatment. Oral m-CPP (0.5 mg/kg body weight) challenge test was performed in 10 patients with status migrainosus occurring within 48 h of the discontinuation of a monophasic pill (30 microg of ethinyl estradiol and 150 microg of desogestrel) and in six healthy women assuming the same OC as controls. In a consecutive menstrual cycle, patients with OC status migrainosus underwent to the same test after they were blindly treated with 2.0 g of percutaneous E2 gel or placebo daily during the pill-free interval. Plasma prolactin and cortisol levels and clinical characteristics of migraine attacks were evaluated. RESULTS: Women with OC-status migrainosus showed a derangement of prolactin release (F = 4.8; P < 0.01) and a lack of cortisol response (F = 5.8; P < 0.001) after m-CPP in comparison with controls. Transdermal E2 during the pill-free interval significantly restored prolactin (F = 2.8; P < 0.01) and cortisol responses (F = 18.9; P < 0.001) against placebo and positively affected the duration (P < 0.001), the number of hours in which pain intensity prohibits daily activity (P < 0.001), the episodes of vomiting (P < 0.001) and the consumption of analgesics (P < 0.001). CONCLUSIONS: Status migrainosus triggered by OC-free interval is associated with impaired prolactin and cortisol responses following m-CPP challenge. Transdermal E2 supplementation is able to restore neuroendocrine response to this specific 5-HT agent, exerting a positive clinical effect on the course of menstrually related migraine. (+info)