Μg Levonorgestrel Research Articles

The response of the pituitary-ovarian axis to pulsatile administration of gonadotropin-releasing hormone in long-term oral contraceptive users

OBJECTIVE: Our purpose was to differentiate between pituitary and hypothalamic feedback effects of oral contraceptives. STUDY DESIGN: Twenty micrograms of gonadotropin-releasing hormone was administered intravenously at 90-minute intervals for 4 days to 14 long-term users of a combined oral contraceptive (30 μg of ethinyl estradiol and 150 μg of levonorgestrel), starting at different moments in the pill cycle. On the fourth day of administration the pulsatile release of luteinizing hormone was determined by blood sampling every 10 minutes for 6 hours. The sensitivity of the pituitary was determined before, during, and after treatment with gonadotropin-releasing hormone by a 100 μg gonadotropin-releasing hormone challenge test. On each sampling day serum estradiol, progesterone, and prolactin levels were measured, and ovarian ultrasonography was performed. RESULTS: After 4 days of pulsatile gonadotropin-releasing hormone administration every exogenous gonadotropin-releasing hormone bolus was followed by an endogenous luteinizing hormone pulse of high amplitude (median 3.30 U/L). Both serum luteinizing hormone and follicle-stimulating hormone levels increased significantly (p < 0.001). The increase in follicle-stimulating hormone levels was accompanied by an increase in serum estradiol (p < 0.01). The luteinizing hormone response to a 100 mg bolus of gonadotropin-releasing hormone decreased during gonadotropin-releasing hormone treatment (p < 0.01), whereas the follicle-stimulating hormone response did not change. CONCLUSION: Pituitary sensitivity is not impaired during oral contraceptive use, suggesting that oral contraceptives exert their negative feedback effects predominantly at the hypothalamic level. (AM J OBSTET GYNECOL 1994;170:462-8.)

Bleeding pattern and climacteric symptoms during different sequential combined HRT regimens in current use

Four sequential combined oestrogen and progestogen regimens were compared in terms of bleeding pattern and relief of climacteric symptoms. Treatment was with either 2 mg 17β-oestradiol with I mg norethisterone acetate [E 2 + NEta]; 2 mg oestradiol valerate with 75 μg levonorgestrel [E 2V + Lng]; 2 mg oestradiol valerate with 10 mg medroxyprogesterone acetate [E 2V + Mpa]; or 1.5 mg 17β-oestradiol with 150 βg desogestrel [E 2 + DG]. A placebo-controlled study lasting 12–24 months was completed by 143 healthy early postmenopausal women. Bleeding lengths were not substantially different; in all regimens the majority of women were bleeding for 3–6 days. Bleeding onset showed differences when related to the 11th day of progestogen addition; in the regimen with E 2V + LNG, 21% of the women were bleeding before the 11th day of progestogen addition 26% on, and 53% after that day. In the regimen with E 2V + MPA, 56% of the women were bleeding before the 11th day, 28% on, and 17% after that day, whereas in the regimen with E 2 + DG, 15% of the women were bleeding before the 11th day, 5% on, and 80% after that day. All regimens reduced climacteric symptoms to the same extent. Breast tenderness occurred in all the regimens, except in the E 2 + DG. Conclusively, the differences between the responses to treatment were not conspicuous. However, our data indicate that one regimen (E 2 + DG) resulted in optimal bleeding control, optimal effect on climacteric symptoms, and no production of breast tenderness.

Levonorgestrel implants as a contraceptive in captive white-tailed deer.

Silastic implants containing levonorgestrel (LNG) were evaluated as a contraceptive in captive white-tailed deer (Odocoileus virginianus). Six adult females and six female fawns received either six or nine implants in autumn. Each implant contained 36 mg of LNG. Blood was analyzed by radioimmunoassay to determine LNG release profile for 5 mo post-implantation. Serum LNG concentrations rose significantly (P = 0.0005) 3 days post-implantation, leveled off after 7 days, and did not change (P = 0.5913) during the remaining 5 mo. Mean (+/- SE) LNG concentrations for all months were higher (P = 0.0377) in adult and fawn females implanted with nine versus six rods (138.1 +/- 14.4 versus 56.7 +/- 12.3 pg/ml, respectively). Serum LNG levels did not differ between adults and fawns. Five of the six implanted adult females had normal estrous cyclicity; three of these five adult females became pregnant in the first year. Four implanted females (two yearlings and two adults) were monitored during a second year, and housed with a fertile buck; three of them became pregnant. We do not recommend the use of LNG in deer.

Systemic availability of levonorgestrel after single oral administration of a norgestimate-containing combination oral contraceptive to 12 young women

Norgestimate is a novel progestin which undergoes both in vivo and in vitro metabolic conversions to a number of metabolites, of which the most important are levonorgestrel acetate, levonorgestrel oxime and levonorgestrel itself. It has been claimed that the progestogenic activity of norgestimate in clinical studies is almost exclusively based on the parent drug and its major metabolite, levonorgestrel oxime, and that levonorgestrel does not make an important contribution. However, to date, no data on the presence of levonorgestrel in the serum of women who have received oral doses of norgestimate have been presented. In the present study, 12 young female volunteers received single oral doses of 250 μg levonorgestrel in combination with 50 μg ethinylestradiol and 250 μg norgestimate in combination with 35 μg ethinylestradiol in an open, randomized, intraindividual comparison. Blood samples were taken at regular time intervals after each treatment, and the serum samples were analyzed for their content of levonorgestrel. Basic pharmacokinetic parameters of levonorgestrel were calculated and from the ratio of the AUC values obtained after both administrations, the bioavailability of norgestimate-derived levonorgestrel was calculated. About 22 ± 6 % of the dose of norgestimate administered became systemically available as levonorgestrel. Thus, it was concluded that levonorgestrel is a major metabolite of orally administered norgestimate, and that at least part of the pharmacologic activity of norgestimate in women is due to the presence of levonorgestrel.

A study comparing the ovarian effects of levonorgestrel and desogestrel given orally and by vaginal ring

SummarySummaryTo compare the effects of two progestagens delivered in two different ways, 40 healthy ovulating volunteers were allocated to four groups. Study design included a control cycle, a study cycle and a recovery cycle. On day two of the menstrual cycle, group 1 used a vaginal ring releasing 20 μg/24 hours of levonorgestrel for 21 days, group 2 and 3 took 30 μg levonorgestrel and 60 μg desogestrel tablets respectively for 21 days. Group 4 used a 3-keto-desogestrel vaginal ring releasing 30 μg/24 hours. The steady state plasma levels with the keto-desogestrel ring did not differ from the trough levels of the 60 μg desogestrel tablets. The release rate from the levonorgestrel containing ring was in a similar relationship to the release rate from the levonorgestrel tablet. Ovulation was inhibited in 4/10 in the levonorgestrel ring group, 8/10 with the levonorgestrel tablet group; no ovulation was seen with the keto-desogestrel tablet or the desogestrel ring. All treatments were associated with persis...

Absence of an effect of high vitamin C dosage on the systemic availability of ethinyl estradiol in women using a combination oral contraceptive

Previous studies in small numbers of women have suggested that the administration of gram quantities of ascorbic acid interferes with the conversion of ethinyl estradiol (EE 2) to its sulfates, leading to higher blood levels of EE 2 The possibility of such potentiation has been investigated in 37 women using a combination monophasic oral contraceptive (30 μg EE 2 and 150 μg levonorgestrel) for two consecutive cycles. Concomitant daily administration of 1 g ascorbic acid taken 1 2 hour before OC intake, was randomly assigned to the first or second cycle of OC use. On the first and 15th day of OC intake, blood samples were drawn 11 times over a 12-hour interval and C max and AUC(0–12 h) calculated. On pill days 10 and 21, only 6-hour post-intake samples were obtained. Samples were analyzed for levels of ascorbic acid, free and sulfated ethinyl estradiol (and a number of other parameters). C max and AUC values for EE 2 and EE 2-sulfate in cycles with and without ascorbic acid were evaluated statistically by the Grizzle model for days 1 and 15 and the ratios of day 15/day 1 for each of the substances. No effect of ascorbic acid was observed ( α = 0.05, 1− β = 0.9). Only on day 15 was there a significantly lower AUC for EE 2-sulfate in the presence of ascorbic acid intake. Thus, the competition between ascorbic acid and EE 2 for sulfation does not lead to an increased systemic availability of EE 2 and is, therefore, unlikely to be of any clinical importance. Ascorbic acid can, therefore, be removed from the list of drugs interfering with the pharmaco-kinetics of ethinyl estradiol.

The TCu-380a (Ag), MLCu375, and Nova-T LUDs and the IUD daily releasing 20 μg levonorgestrel-four pillars of IUD contraception for the nineties and beyond?

With recent studies repeatedly showing results clearing the IUDs from their formerly suspected role in causing pelvic inflammatory disease (PID), very likely IUD use will further increase worldwide. While most previous IUDs have been withdrawn from the US market during the 1980s, newer and more effective IUDs have subsequently been developed; and some, marketed. Four of these devices will probably become the pillars for future IUD contraception worldwide. This review evaluates the relative performance and safety of these four devices. Consistent findings have proven the Copper-T 380A (Ag) and the Multiload-375 (MLCu375) IUDs to be safe with high and long-lasting efficacy. The Nova-T IUD showed favorable results in some studies, but showed deteriorated efficacy after three years of use in others; more studies are needed. Studies show that the IUD that daily releases 20 μg levonorgestrel (LNG-20) is associated with the highest efficacy in preventing accidental pregnancy among the four devices, but it has a uniquely high medical removal rate because of amenorrhea. This steroid-releasing device could be a high-performance IUD if this type of medical removal can be reduced through patient counseling devised according to local cultural background.

An objective and subjective assessment of uterine blood loss in postmenopausal women on hormone replacement therapy

Objective To determine the volume of withdrawal blood loss in women taking hormone replacement therapy (HRT). Design Prospective randomized double blind cross-over trial. Subjects Twenty-nine postmenopausal women, with climacteric symptoms. Interventions The women were treated with cycles of 2 mg oestradiol valerate for 21 days combined with either 250 μg levonorgestrel or 10 mg medroxyprogesterone acetate, for the last ten days. Each woman was randomly allocated to one of the preparations and switched to the other after four months. Twenty-nine postmenopausal women, with climacteric symptoms. Main outcome measures Uterine blood loss was estimated by the alkaline haematin method. Bleeding patterns were recorded specifying the number of days with bleeding and subjective rating of the amount of blood lost. Results and conclusions The mean uterine blood loss was 35.2 ml and was equivalent to the normal menstrual blood loss. There was no significant difference between therapies but the women themselves considered that they bled more heavily when taking the levonorgestrel combination. The intraindividual variation in blood loss was small, independent of preparation taken, but the variation between individuals was large. Withdrawal bleeding started 2–3 days earlier when the women used the medroxyprogesterone acetate compared to the levonorgestrel formulation.

Correction: Starting oral contraceptives (25 May, page 43)

Norgestrel, contained in the progestagen-only pill Neogest, is not, as we said, a ‘newer’ progestagen but a mixture of 37.5μg levonorgestrel and 37.5μg of dextronorgestrel which has no progestagenic activity.

A cross-over study of three oral contraceptives containing ethinyloestradiol and either desogestrel or levonorgestrel

A randomised cross-over trial was performed to compare the pharmacodynamic actions of three low-dose oral contraceptives (OCs): Marvelon (150 μg desogestrel (DSG) + 30 μg ethinyloestradiol (EE)), Mercilon (150 μg DSG + 20 μg EE) and Microgynon (150 μg levonorgestrel (LNG) + 30 μg EE). None of the OCs produced any significant changes in serum cholesterol, LDL-C and apoprotein B. Triglycerides were increased by the desogestrel OCs but not by Microgynon. The latter however increased the glucose and insulin responses to a glucose tolerance test whereas Marvelon and Mercilon had no effect. HDL-C increased with Marvelon, was unchanged with Mercilon and was decreased with Microgynon. Apoprotein AII was increased by all three OCs but only the DSG OCs increased apoprotein AI. All OCs produced similar increases in caeruloplasmin but the increase in SHBG was much greater with Marvelon and Mercilon than with Microgynon. Testosterone was reduced more with Microgynon than with the DSG OCs. Many of the changes reflect the strong anti-oestrogenic action of LNG on metabolic parameters compared to DSG. Except for the effect on HDL-C, there was little difference between Marvelon and Mercilon on metabolic parameters and this complements the findings from large-scale clinical trials of the two OCs. Mercilon, therefore, provides a very satisfactory alternative to Marvelon.

Intrasubject variability in the pharmacokinetics of ethynyloestradiol

Intrasubject and intersubject variability in the metabolism of ethynyloestradiol (EE) was assessed in a cross-over randomized study of 6 women who each received 3 months treatment with 50 μg EE and 50 μg EE with 250 μg levonorgestrel (LNG). Blood samples were collected at the end of each treatment month, assayed for EE and the half-life of elimination ( T el and bioavailability (area under the serum concentration-time curve, AUC) calculated. Intrasubject variability for T el and AUC varied markedly; the variability was random and not correlated with the formulation administered. The intrasubject variability for T el and AUC was 31 and 17%, respectively, and intersubject variability 66 and 95%. The intersubject range of values was more than 3-fold for both T el and AUC and the intrasubject range about 2-fold. The pharmacokinetics of EE were not influenced by LNG; mean values for T el and AUC were 17.3 ± 5.5 h and 11.1 ± 3.8 ng/ml/h, respectively, when EE was administered alone compared with 16.4 ± 4.8 h and 12.5 ± 3.9 ng/ml/h when given with LNG. However, EE influenced the metabolism of LNG; T el for LNG was 19.3 ± 4.2 h when administered alone and significantly higher (30.0 ± 11.2 h) when given with EE. There was no correlation between the rate of metabolism of EE and that of LNG. The intrasubject variability shown in this and other studies suggests that genetic factors are less important in intersubject variability than previously thought. Some implications of intrasubject variability are discussed.

Serum lipids, lipoproteins, and apolipoproteins during postmenopausal estrogen replacement therapy combined with either 19-nortestosterone derivatives or 17-hydroxyprogesterone derivatives

To study the influence of combined hormone replacement therapy on levels of serum lipids, lipoproteins, and apolipoproteins. One hundred thirty-nine healthy early postmenopausal women selected by means of a questionnaire, a medical examination, and a laboratory screening procedure to be a representative sample of postmenopausal Danish women aged 45 to 55 years old were randomized to four treatment and two placebo groups. The four groups receiving hormone replacement therapy were given 2 mg estradiol valerate equivalents (E), either sequentially combined with 75 micrograms levonorgestrel (E/LNG), 10 mg medroxyprogesterone acetate (E/MPA), or 150 micrograms desogestrel (E/DG), or continuously combined with 1 mg cyproterone acetate (E/CPA). Serum lipids, lipoproteins, and apolipoproteins were measured before institution of hormone replacement therapy and at nine well-defined times during the following 84 days. Total response and cyclical variations were calculated. All active treatment regimens reduced serum low-density lipoprotein cholesterol (LDL-C) significantly: E/CPA, 6% (95% confidence limits 0.3% to 11.3%); E/LNG, 10.9% (4.9% to 16.6%); E/MPA, 14.4% (7.4% to 20.9%); E/DG, 10.7% (3.3% to 17.6%). The changes in serum total cholesterol and apolipoprotein B were similar but smaller than those in LDL-C. None of these treatment regimens induced significant overall changes in serum high-density lipoprotein cholesterol (HDL-C) or apolipoprotein A1 (Apo A1). The sequentially combined hormone treatments induced significant cyclical variations in HDL-C, with an increase during estrogen therapy and a decrease during combined therapy: E/LNG, 13.3% (7.4% to 19.4%); E/MPA, 6.9% (1.6% to 12.6%); E/DG, 10.3% (5.8% to 14.9%). No cyclical changes in HDL-C were found in the group receiving continuously combined hormone replacement therapy (E/CPA). The changes in Apo A1 parallel those in HDL-C. All the treatment regimens produced changes in levels of serum lipids, lipoproteins, and apolipoproteins that may be considered favorable in terms of cardiovascular disease.

The effect on follicular growth and luteal function of “missing the pill”: A comparison between a monophasic and a triphasic combined oral contraceptive

The effects on follicular growth and hormonal indices of the deliberate omission of two low-dose combined oral contraceptives, a monophasic (30 μg ethinylestradiol + 150 μg desorgestrel) and a triphasic (30 μg ethinylestradiol + 50 μg levonorgestrel for 6 days, followed by 40 μg ethinylestradiol + 75 μg levonorgestrel for 5 days and 30 μg ethinylestradiol + 125 μg levonorgestrel for 10 days) combination during the first three days of one contraceptive pill cycle was studied in two groups of 10 women each. Follicular growth was followed by ultrasound scanning and plasma levels of estradiol, and progesterone were measured every other day until day 19 of the contraceptive pill cycle. In each group, ovulation occurred in one subject and 4 women reacted with follicular activity only, while 5 women on the monophasic and 3 on the triphasic formulation exhibited complete ovarian suppression. Two subjects on the triphasic preparation showed follicular growth followed by insufficient luteal function. Thus, the risk of escape ovulation when the pill-free interval is prolonged to 10 days in women taking low-dose combined oral contraceptive pills, is low ( 1 10 ).

Serum lipids, lipoproteins, and apolipoproteins during postmenopausal estrogen replacement therapy combined with either 19-nortestosterone derivatives or 17-hydroxyprogesterone derivatives

purpose: To study the influence of combined hormone replacement therapy on levels of serum lipids, lipoproteins, and apolipoproteins. patients and methods: One hundred thirtynine healthy early Postmenopausal women selected by means of a questionnaire, a medical examination, and a laboratory screening procedure to be a representative sample of postmenopausal Danish women aged 45 to 55 years old were randomized to four treatment and two placebo groups. The four groups receiving hormone replacement therapy were given 2 mg estradiol valerate equivalents (E), either sequentially combined with 75 μg levonorgestrel (E/LNG), 10 mg medroxyprogesterone acetate (E/MPA), or 150 μg desogestrel (E/DG), or continuously combined with 1 mg cyproterone acetate (E/CPA). Serum lipids, lipoproteins, and apolipoproteins were measured before institution of hormone replacement therapy and at nine well-defined times during the following 84 days. Total response and cyclical variations were calculated. results: All active treatment regimens reduced serum low-density lipoprotein cholesterol (LDL-C) significantly: E/CPA, 6% (95% confidence limits 0.3% to 11.3%); E/LNG, 10.9% (4.9% to 16.6%); E/MPA, 14.4% (7.4% to 20.9%); E/DG, 10.7% (3.3% to 17.6%). The changes in serum total cholesterol and apolipoprotein B were similar but smaller than those in LDL-C. None of these treatment regimens induced significant overall changes in serum high-density lipoprotein cholesterol (HDL-C) or apolipoprotein A 1 (Apo A 1). The sequentially combined hormone treatments induced significant cyclical variations in HDL-C, with an increase during estrogen therapy and a decrease during combined therapy: E/LNG, 13.3% (7.4% to 19.4%); E/ MPA, 6.9% (1.6% to 12.6%); E/DG, 10.3% (5.8% to 14.9%). No cyclical changes in HDL-C were found in the group receiving continuously combined hormone replacement therapy (E/CPA). The changes in Apo A 1 parallel those in HDL-C. conclusion: All the treatment regimens produced changes in levels of serum lipids, lipoproteins, and apolipoproteins that may be considered favorable in terms of cardiovascular disease.

Plasma Estriol Levels after Intramuscular Injection of Estriol and Two of Its Esters&lt;sup&gt;1&lt;/sup&gt;

Twelve female volunteers from Berlin and 9 from Stockholm, all using a contraceptive pill (30 micrograms ethinyl estradiol and 150 micrograms levonorgestrel), received an intramuscular injection of estriol (E3; 1 mg in oil) on day 5 of withdrawal bleeding. Blood samples were collected at increasing time intervals during 4 weeks. Three months later, on day 5 of their withdrawal bleeding, 6 women were given intramuscularly (in oil) estriol 3,17-dipropionate (E3-prop) and 15 women estriol 3,17-dihexanoate (E3-hex). The doses were equivalent to 5 mg of estriol, i.e. 6.94 and 8.90 mg, respectively. Blood samples were collected during a period of 9 weeks. Estriol was analyzed by radioimmunoassay in all plasma samples. The average half-life of E3 ranged from 1.5 to 5.3 h after the administration of E3. It was 12.7 h and between 187 and 221 h after the administration of E3-prop and E3-hex, respectively. The average areas under the curve (in nmol.l-1.h) of E3 were between 82.5 and 161 after the administration of E3-prop or E3-hex, and between 27.1 and 37.9 when E3 had been given. As E3 was administered in a 5-fold lower dose than the esters, the areas under curve appeared to be comparable. Thus, the total exposure to E3 seemed to be almost independent of the type of E3 derivatization, while the time and intensity of exposure were very different.

A comparative study of the effects of a monophasic and a triphasic oral contraceptive containing ethinyl estradiol and levonorgestrel on lipid and lipoprotein metabolism

A comparative study of the effects of a monophasic and a triphasic oral contraceptive containing ethinylestradiol (EE) and levonorgestrel (LNG) on lipid and lipoprotein metabolism was conducted on 45 Singapore women under the WHO Special Programme of Research in Human Reproduction. The women were randomly allocated to one of the two pill groups — a triphasic preparation containing low doses of LNG and EE in various proportions and a monophasic preparation of 150 μg LNG and 30 μg EE, and an additional 18 women, choosing to use IUDs, were recruited as controls. Blood samples were taken at admission, 3 and 12 months thereafter. For both pill groups, total cholesterol decreased with duration of use, while HDL cholesterol decreased slightly at 3 months and thereafter increased. LDL cholesterol decreased slightly at 3 months, returning to baseline at 12 months for the monophasic group, while remaining unchanged at 12 months for the triphasic group. The monophasic preparation appeared to lower total, LDL and HDL cholesterols to a greater extent at 3 months than the triphasic preparation. Compared with IUD users, for the monophasic group, both total and HDL cholesterols were significantly lower at 3 months and HDL and LDL cholesterols were lower at 12 months. In addition, ratios of HDL cholesterol/LDL cholesterol and HDL cholesterol/total cholesterol were significantly lower at 12 months. Changes in triglycerides were minimal for both pill groups. However, at 3 months, triglycerides for the triphasic group were significantly higher than the IUD users, but this observation was not of any clinical importance since comparison of changes with their respective pretreatment values were not statistically significant. These results indicate that these changes are related to the dosage and estrogen-progestogen ratio of the preparation. Furthermore, the monophasic preparation may have a disadvantage over the triphasic preparation since it appears to cause more disturbance in lipid metabolism. However, it is noted that these changes in lipids and lipoproteins were minimal and did not appear to be of any clinical significance.

Vaginal Ring is Effective For at Least One Year, Worldwide Trials Show

Clinical trials of the Silastic 382 vaginal ring indicate that it is an effective contraceptive method for at least 1 year of use. The trials were conducted during 1980-86 with the vaginal ring being tested in 19 centers in 13 countries (Africa Asia Europe and Latin America). The vaginal ring developed by the WHO contains a core of 5 mg of levonorgestrel and must be replaced every 90 days. Specifically it releases 20 mcg of levonorgestrel every 24 hours. 1005 women aged 19-34 were selected for the study. The pregnancy rate with the device in place was 3.7 per 100 women at the end of 1 year. The 1-year discontinuation rate was 50%. This is attributable to loss to follow-up menstrual problems vaginal irritation desire to become pregnant and expulsion of the ring either through defecation menstruation urination strenuous activity or intercourse. The investigators conclude that the contraceptive efficacy and medical safety of the WHO vaginal ring are comparable to other low-dose progestogen-only contraceptives for at least 1 year of use.

Pituitary, ovarian and endometrial effects of 300 μg norethisterone and 30 μg levonorgestrel administered on cycle days 7 to 10

The ovarian, endometrial and pituitary effects of 300 μg norethisterone (NET) and 30 fig levonorgestrel (L-NOG) administered orally on cycle days 7–10 were investigated in two groups of 10 women each, by daily analysis of plasma estradiol (E 2), progesterone (PROG), immunoreactive luteinizing hormone (LH) and follicle stimulating hormone (FSH) in a pretreatment control cycle and during NET or L-NOG administration. Endometrial biopsies were obtained for morphometric analysis on cycle day 11 in the control and treatment cycles. Treatment with 300 μg NET resulted in an increase in the area under the E 2 peak (p<0.05), reduction in the number of subjects with normal progesterone profile (p<0.05) and a decrease in the area under the progesterone curve (p<0.05). The treatment suppressed the LH peak in 4 subjects and progesterone in 4 subjects. The follicular phase was prolonged in one subject, Norethisterone induced marked subnuclear vacuolation in the endometrium, while the glandular mitoses were decreased during NET treatment. Treatment with 30 μg L-NOG resulted in a decrease in subjects with normal progesterone profiles (p<0.05) and in the area under the progesterone curve (p<0.05). The treatment suppressed the LH peak in 3 subjects and progesterone in 4 women. The follicular phase was prolonged in one subject. L-NOG did not significantly increase the diameter of glands or induce subnuclear vacuolation in the endometrial glands.

Interactions between the oral contraceptive pill and antibiotics

To determine whether the efficacy of oral contraceptives (OCs) is diminished by concurrent antibiotic treatment 124 female acne patients at a UK clinic who were receiving combined drugs were surveyed. Cumulatively the survey encompassed 163 woman-years of experience with concomitant OC-antibiotic use. There were 2 pregnancies reported. The 1st involved a patient who was on longterm minocycline for acne and was taking Brevinor (35 mg of estrogen and 500 mg of norethisterone). The 2nd patient had taken oxytetracycline for 5 days while on Microgynon (30 mg of estrogen and 150 mg of levonorgestrel). This failure rate represents a 6-fold increase over the expected OC failure rate of 2/1000 woman-years. Although further research with larger number of cases is needed the findings of this study would suggest that women who are receiving antibiotics and other conditions should be prescribed alternative forms of contraception.

Microdose intravaginal levonorgestrel contraception: A multicentre clinical trial: II. Expulsions and removals

This paper investigates the relationship between expulsions and removals, and demographic characteristics of 1005 women from 19 centres using a vaginal ring releasing 20 μg levonorgestrel per 24 hours. Emphasis is placed on discontinuations of method use due to expulsions, on the number and rate of expulsions, and the time at which the first expulsion occurred.The overall life-table discontinuation rate due to expulsion was 7.1% at one year. Life-table discontinuation rates increased with parity and were highest in Asian and lowest in European women. In respect to the number of expulsions experienced by women (expulsions did not necessarily lead to discontinuation), the women of high parity and those from Asia and Europe have the highest rates.The life-table first expulsion rate is 29% at one year. Such rates are highest in Chinese and Asian women. Following a first expulsion, the second expulsion rate is 45% by the end of the subsequent six months. The majority of first expulsions occur at defaecation (134 or 57% of 234 women), urination (12%) and during menstruation (17%).Rings were removed by 121 (12%) women on 201 occasions and for a variety of reasons. The main medical reasons were vaginal discharge and irritation, bleeding pain and dyspareunia. Others removed the ring during defaecation, intercourse or because the ring came out of place. Women also removed rings for curiosity, to show their husbands and to clean.