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

The ovarian, endometrial and pituitary effects of 300 micrograms norethisterone (NET) and 30 micrograms 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 (E2), 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 micrograms NET resulted in an increase in the area under the E2 peak (p less than 0.05), reduction in the number of subjects with normal progesterone profile (p less than 0.05) and a decrease in the area under the progesterone curve (p less than 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 micrograms L-NOG resulted in a decrease in subjects with normal progesterone profiles (p less than 0.05) and in the area under the progesterone curve (p less than 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.     

The effect of follicular growth and luteal function of "missing the pill". A comparison between a monophasic and a triphasic combined oral contraceptive

The effects of follicular growth and hormonal indices of the deliberate omission of two low-dose combined oral contraceptives, a monophasic 130 micrograms ethinylestradiol + 150 micrograms desorgestrel) and a triphasic (30 micrograms ethinylestradiol + 50 micrograms levonorgestrel for 6 days, followed by 40 micrograms ethinylestradiol + 75 micrograms levonorgestrel for 5 days and 30 micrograms ethinylestradiol + 125 micrograms 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).     

Clinical experience and pharmacological effects of an oral contraceptive containing 20 micrograms oestrogen.

The performance of a new low-dose oral contraceptive (Mercilon) containing only 20 micrograms ethinyloestradiol combined with 150 micrograms desogestrel is reviewed. Eight multicentre clinical trials have been completed and provide information on 10,672 women studied over 73,477 cycles. The high efficacy of Mercilon was indicated by the finding that only 10 pregnancies were reported; nine of these occurred in women who omitted to take Mercilon on a number of days and only one in a woman who took all the tablets according to instructions. Cycle control was good; as with all oral contraceptives, the incidence of breakthrough bleeding and spotting was highest in the first treatment cycle and by the sixth treatment cycle the values were usually < 5% and < 7%. More than 80% of women had regular cycles. Side effects were few, the most common being headache, nausea and breast tenderness with incidences in the sixth treatment cycle of less than 2%, 6% and 6%, respectively. There were no significant changes in body weight or blood pressure. Pharmacodynamic investigations showed no adverse effects. Only 1 of 5 studies found an increased response to a glucose tolerance test compared to the pretreatment test. In 8 of 10 studies, serum HDL-C concentrations increased on treatment and this was associated with increases in apoproteins A1 and A2. Serum triglyceride levels also increased but no change occurred in serum cholesterol or LDL-C levels. Haematological factors were assessed in 8 studies and only minor changes were observed. Serum binding protein (SHBG, CBG, caeruloplasmin) concentrations increased and serum androgen levels decreased. Measurements of blood FSH, LH, oestradiol and progesterone indicated adequate inhibition of ovulation. Mercilon is the only oral contraceptive containing 20 micrograms ethinyloestradiol to have high efficacy, to have no adverse pharmacodynamic effects and, importantly, to produce an acceptable bleeding pattern not significantly different from that of oral contraceptives with a higher content of ethinyloestradiol.     

Regulation of non-pregnant human uterine contractility. Effect of antihormones

Uterine contractility was recorded on cycle day LH+6 to LH+8 in a control and treatment cycle in 14 healthy non-pregnant volunteers. In the treatment cycle the subjects received either 50 mg of the antiprogestin RU 486 daily for three days or 40 mg of the anti-estrogen tamoxifen daily for two days. The treatment started on day LH+2. During the recording, 2 to 5 micrograms PGF2 alpha was administered into the uterine cavity. The plasma levels of progesterone and estrogen were the same in both the control and treatment cycles. RU 486 caused a significant increase in uterine contractility expressed in Montevideo Units (MU) and a decrease in uterine tonus in comparison with corresponding data obtained in the control cycle. Following treatment with tamoxifen, uterine contractility was lower but the difference was not significant. PGF2 alpha invariably caused a stimulation of uterine contractility. However, treatment with the antihormones did not influence the response. The result of the present study indicates that the change in uterine contractility occurring in the latter part of the menstrual cycle and during menstruation is due to progesterone withdrawal.     

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 (E₂), 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 E₂ 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.     

The effect of deliberate omission of Trinordiol or Microgynon on the hypothalamo-pituitary-ovarian axis

The effect of deliberate omission of a phased formulation pill, Trinordiol (ethinyl estradiol 30 micrograms + levonorgestrel 50 micrograms: 6 tablets; ethinyl estradiol 40 micrograms + levonorgestrel 75 micrograms: 5 tablets; ethinyl estradiol 30 micrograms + levonorgestrel 125 micrograms: 10 tablets) or a low-dose, combined, oral contraceptive pill, Microgynon (ethinyl estradiol 30 micrograms + levonorgestrel 150 micrograms: 21 tablets) on the hypothalamo-pituitary-ovarian axis were studied. Thirty-six women were recruited to the study and divided equally between the two types of pill. Medication was begun on the 8th pill-free day of the cycle and continued for 7 days (Group 1), 14 days (Group 2) or 21 days (Group 3). Levels of FSH, LH, estradiol (E2) and progesterone (P) were measured in plasma on alternate days during the final week of pill therapy, and daily for the 7 days after stopping the pill. For the first 2 weeks of pill therapy, follicular activity, as judged by plasma levels of E2, was greater in women taking Trinordiol than in those taking Microgynon, but was similar in both groups by the third week of pill treatment. Five women taking Trinordiol (2 in Group 1 and 3 in Group 2) had plasma levels of E2 in excess of 500 pmol/l whilst taking the pills, and only 1 patient achieved this degree of follicular activity after stopping the tablets. One woman who had taken 7 days of Trinordiol (Group 1) showed a rise of plasma levels of P to 6.8 nmol/l, but luteinization did not occur in any of the remaining 35 women who took Trinordiol or Microgynon. These findings suggest that follicular activity is less completely suppressed by Trinordiol than Microgynon, at least in the first 2 weeks of pill therapy, but that normal ovulation is still a rare event in the week after cessation of either of these pills, even if only 7 days of medication have been taken.     

Miniature ponies: 2. Endocrinology of the oestrous cycle

Plasma concentrations of FSH, LH, oestradiol and progesterone were studied daily during 12 interovulatory intervals and 21 periovulatory periods in nine Miniature ponies. The peak of the FSH surge that was temporally associated with emergence of the future ovulatory follicle occurred when the follicle was approximately 9 mm, compared with a reported diameter of 13 mm in larger breeds. The ovulatory LH surge involved a slow increase between Days 13 and 18 (ovulation=Day 0; 0.6+/-0.1 ng day(-1)), a minimal increase or a plateau on Days 18 to 21 (0.04+/-0.1 ng day(-1)), and a rapid increase after Day 21 (2.2+/-0.4 ng day(-1); P<0.0001). The end of the plateau and the beginning of the rapid increase occurred on the day of maximum concentration in the oestradiol preovulatory surge. An unexpected mean increase and decrease in LH occurred (P<0.04) on Days 5 to 9. Concentrations of oestradiol and progesterone seemed similar to reported results in larger breeds. Results indicated that in Miniature ponies the peak of the FSH surge associated with emergence of the future ovulatory follicle occurred at a smaller diameter of the future ovulatory follicle than in larger breeds, the ovulatory LH surge increased in three phases, and the ovulatory LH surge was followed by an LH increase and decrease during the early luteal phase.     

Effect of depo-medroxyprogesterone acetate on serum progesterone levels when administered on various cycle days

Depo-medroxyprogesterone acetate (DMPA) in the conventional dose of 150 mg, was administered intramuscularly to 49 healthy, already sterilized, Thai women on cycle day 5 (13 subjects), day 7 (12 subjects), day 9 (13 subjects) and day 11 (11 subjects) of normal menstrual cycles. Serum progesterone levels were then monitored in order to ascertain the latest follicular phase day in the cycle (up to day 11) when ovulation would be inhibited in the first month after injection. Among the 25 subjects who received DMPA on day 5 and 7, no longitudinal serum progesterone level rises indicative of ovulation were detected. When DMPA was given on day 9 and 11, 2 out of 13 subjects (15.39%) and 3 out of 11 subjects (27.28%), respectively, had serum progesterone levels characteristic of ovulation. It is concluded that the initial cycle's ovulation can also be inhibited when DMPA is administered on day 7 of that cycle. However, DMPA administered on day 9 and 11 failed to inhibit ovulation of that cycle in some of the subjects.     

Using the ratio of urinary oestrogen and progesterone metabolites to estimate day of ovulation

We have developed a method of estimating day of ovulation using urinary ovarian hormone data. The method identifies a day of luteal transition that occurs at the shift from production of follicular oestrogen to luteal progesterone. The algorithm for identifying this shift was evaluated and judged better than specified alternatives in that it resulted in (1) a high concordance between the day of luteal transition and peaks in urinary luteinizing hormone (LH) for cycles with well-defined peaks, (2) a low variance in the length of the luteal phase of the menstrual cycle, which presumably reflects a low measurement error in estimating day of ovulation, and (3) a high proportion of cycles for which an approximate day of ovulation could be determined. To validate the new algorithm, it was applied to an independent data set. The algorithm identified a day of luteal transition in 88 percent of these cycles, and the identified day occurred within two days of the urinary LH peak for all of the cycles with clear LH peaks. Determination of the day of luteal transition to estimate ovulation requires only first-morning urine specimens, requires no correction for day-to-day variations in urine concentration, and can be applied to a mid-ycle window of data.     

Effect of oral administration of a continuous 18 day regimen of meloxicam on ovulation: experience of a randomized controlled trial

Background

Cyclooxygenase-2 (COX-2) is expressed in all female reproductive organs. Therefore, inhibitors of COX-2 may affect reproductive function. We evaluated the effect of extended administration of meloxicam on ovulation and the menstrual cycle. Our hypothesis was that meloxicam administered from menstrual cycle day 5- 22 could interfere with follicular rupture, without disrupting the menstrual cycle, and could be a potential non-hormonal contraceptive method.

Methods

The study was conducted in 56 healthy sterilized women. Before the onset of treatment and after the end of treatment, participants were observed during a control cycle to ensure that they had progesterone (P₄) serum levels (> 12 nmol/l) consistent with ovulation. Participants were treated for 18 days, during three consecutive cycles. They were randomized to 15 or 30 mg/day. The menstrual cycle was monitored with serial ultrasound and hormone assays in blood.

Results

Fifty-six volunteers completed the study. In 55% of cycles treated with 15 mg/day and in 78% of cycles treated with 30mg/day (p<0.001) we observed dysfunctional ovulation defined as follicular rupture not preceded 24–48 h earlier by an LH peak or preceded by a blunted LH peak (< 21 IU/l) or not followed by an elevated serum P₄ level > 12 nmol/l. Ovulation was observed in 44.6% and in 21.7% of women in the lower dose group and the higher dose group, respectively. There were no differences between the two doses in other parameters measured. There were no serious adverse events and adverse events were not different between doses or between control and treated cycles.

Conclusions

Although administration of meloxicam on menstrual cycle days 5- 22 resulted in a dose-dependent inhibition of ovulation, more than 20% of subjects had normal ovulation with the highest dose.

Implications

Previous studies have shown that oral meloxicam can delay follicle rupture. This study investigated daily oral meloxicam as a non-hormonal contraceptive. Since ovulation occurs in over 20% of cycles even with a high dose of 30 mg daily, it is not likely that the approach would be a highly effective contraceptive strategy.     

Immediate postabortal contraception with a microdose combined preparation: gonadotropin, estradiol and progesterone levels during the last treatment cycle and after discontinuation of oral contraceptives

The concentrations of plasma LH, FSH, estradiol, and progesterone, as well as urinary LH, were measured during the last treatment cycle and during the recovery cycle in women who, immediately after abortion, had started microdose combined oral contraceptives containing 30 μg of ethinylestradiol and 150 μg of d-norgestrel.During the treatment, cyclic variations were found in LH, FSH, and estradiol concentrations. FSH levels were highest during the first treatment week as well as the treatment-free week. LH concentrations were highest during the first treatment week. Estradiol concentrations showed a significant increase during the treatment-free week and during the first treatment week suggesting a follicle stimulation.The recovery of ovulation occurred rapidly, in a great majority of the subjects, after discontinuation of the treatment. The first midcycle LH peak was observed thirteen days after the intake of the last pill, and 50% of the subjects had ovulated within 22 days. In 91% of the subjects, plasma progesterone concentration during the luteal phase was higher than 5 ng/ml.     

Intermittent GnRH antagonist plus progestin contraception conserving tonic ovarian estrogen secretion and reducing progestin exposure

The present study was designed to evaluate the effectiveness of a once-weekly regimen of GnRH antagonist followed by a progestin as a potential new contraceptive method. On menstrual cycle days 2, 9, 16, and 23 (onset of menses = Day 1) monkeys were divided into two groups: 1) those injected sc with 0.1 mg/kg Nal-Glu GnRH antagonist in saline and those given only vehicle (control). On cycle days 15 to 26, each treated female was administered 25 micrograms norgestimate/day orally. This was continued for three treatment cycles (84 days). Weekly injections of Nal-Glu GnRH antagonist effectively blocked completion of folliculogenesis, ovulation, and corpus luteum function as judged by serum LH, E2, and P levels. Serum progesterone was undetectable (less than 0.1 ng/ml) during the treatment cycles. Importantly, serum estradiol levels during GnRH antagonist plus norgestimate treatments were maintained at 35 +/- 7 pg/ml. Upon the cessation of norgestimate treatment on day 26 in each cycle, menses uniformly began within 2 or 3 days. Regarding recovery, apparently normal and presumably ovulatory menstrual cycles, as judged by timely estradiol elevations, midcycle LH surges, and luteal phase progesterone patterns, were manifest immediately following termination of the final GnRH antagonist plus norgestimate treatment cycle. Endometrial biopsies removed on day 26 of control cycles, and on day 26 of the third treatment cycle revealed appropriate late secretory phase endometrium having tortuous endometrial glands and superficial stromal edema. Histological sections of ovaries removed at the end of the GnRH antagonist plus norgestimate treatment revealed multiple small and medium-sized developing and atretic follicles, having maintained serial ablation of the potentially maturing follicles.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of oral contraceptives on integrated secretion of gonadotropins.

The mechanism of action of various oral contraceptives has not yet been satisfactorily resolved, as to how gonadotropins affect ovarian function. Alterations of the pulsatile release of LH might be a common denominator. As methodological difficulties for the evaluation of LH pulse pattern with low basal levels exist, we elected to determine the area under the curve (AUC) for LH and FSH for 6 hours before and during treatment with oral contraceptives. LH and FSH were determined every 15 min for 6 hours on day 4 and day 20 of a control cycle and a treatment cycle in 22 women with ovulatory cycles. They received either a combined preparation containing 150 micrograms desogestrel and 30 micrograms ethinyl estradiol, a sequential preparation containing 50 micrograms of ethinyl estradiol and 125 g of desogestrel or only 125 micrograms desogestrel. There was no difference between the sum of LH pulses on day 4 and day 20 of the control cycle. The AUC for FSH was lower on day 20. When the combined preparation was taken, FSH was suppressed on day 4, and FSH and LH on day 20 of treatment. The degree of suppression was even more pronounced when the sequential OC was taken. Ethinyl estradiol alone was as effective as the combination with desogestrel. Desogestrel alone inhibited ovulation without affecting serum LH and FSH in a comparable manner, suggesting a direct effect on the ovary. The determination of the AUC seems to be a sensitive tool for the evaluation of OC-induced changes in gonadotropin output.     

Evaluation of endocrine parameters in clinical trials with beta-hCG vaccine.

This report presents data on various endocrine parameters with respect to pituitary-ovarian axis in-depth in control vs 18 subjects immunized with three beta-hCG based vaccine formulations. Hormonal parameters such as TSH, PRL, ACTH, progesterone, cortisol, T3 and T4 were measured by RIA in sera in control pre-vaccine cycles as well as at 3, 6, and 12 months after primary vaccine immunization. In 6 women urinary E1G, PdG, LH and FSH were measured by ELISA/RIA tests on early morning urine (EMU) samples collected throughout the menstrual cycle in control vs post-booster vaccine cycles. The results indicated that none of the beta-hCG vaccine formulations altered the pituitary peptide or steroid hormone levels in blood at any time during the period of study. Serum P concentration was adequate and indicative of ovulatory cycle in almost all the cycles during the study. The in-depth study on urinary excretion pattern and levels of gonadotropins and E1G and PdG throughout the control vs post-vaccine booster cycles conclusively showed that pituitary-ovarian axis was not adversely affected by the vaccine.     

Opioid involvement in LH release during the negative feedback effects of oestradiol and progesterone in dairy cows.

To create a clearly defined and uniform feedback phase of oestradiol, 1 mg oestradiol benzoate (OE2) was injected i.m. either 15-43 days post partum in 7 cows (Expt 1), or 12 h after prostaglandin oestrus synchronization of 4 cyclic cows (Expt 2 and 3). An endogenous opioid peptide (EOP) antagonist (250 mg naloxone), an EOP agonist (300 mg morphine), or a combination of the two was given in Expt 1, 2 and 3 respectively as a single i.v. injection in cows 16-18 h after OE2, i.e. in the negative feedback phase and before the expected onset of an induced luteinizing hormone (LH) surge. Blood samples were collected every 15 min for 1 h before and 2 h after each treatment. In Expt 1, naloxone failed to increase LH release when given during the negative feedback phase, but caused excessive release in one cow in which the LH surge had just begun. In all cows in Expt 2, morphine suppressed LH release (P less than 0.05). In Expt 3, naloxone prevented the suppressive effects of morphine for the first hour after treatment; a transient rise in LH occurred in one cow in which treatment was given 1 h before the start of the LH surge. In Expt 4, 250 mg naloxone was injected i.v. into 4 cows that had a plasma progesterone concentration of 1.5-3.1 ng mL-1 in the luteal phase of the oestrous cycle: naloxone failed to increase LH concentrations. It is concluded that LH can be further suppressed by opiates given to cows during the negative feedback phase of oestradiol.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of intranasal administration of norethisterone on folliculogenesis, cervical mucus, vaginal cytology, endometrial morphology and reproductive-endocrine profile in women.

The effects of intranasal administration of norethisterone (NET) on menstrual cycle length, folliculogenesis, serum levels of estradiol, FSH, LH and progesterone, vaginal cytology, cervical mucus and endometrial morphology were studied in 8 volunteers (age 28 to 39 years, weighing between 46 and 54 kg). The study period comprised 4 consecutive menstrual cycles. In the first cycle (pretreatment cycle), only the vehicle (alcohol, propylene glycol, water; 3:3:4) was sprayed intranasally (100 microliters in each nostril), using a metered nebulizer, once daily from day 3 to the last day of menstrual cycle. In the next two cycles (treatment cycles), NET (300 micrograms/day) was administered once daily, starting from day one of menstrual cycle, between 9 and 10 a.m. The fourth cycle was a post-treatment cycle in which the volunteers were monitored for recovery. Blood samples (about 5 ml each) were collected once daily from day 8 to 24 and thereafter on alternate days until the last day of cycle during all the 4 cycles. Levels of estradiol, FSH, LH and progesterone were measured in the serum samples by radioimmunoassay methods. Cervical mucus samples and vaginal smears were collected once daily starting from day 7 or 8 of each cycle until the mucus was very scanty. Serial pelvic ultrasonography was performed starting from day 7 or 8 until the growing follicle disappeared or throughout the cycle in case a growing follicular cyst was observed. Endometrial aspirates were collected once around day 22 in each cycle and processed for routine histological examination.     

Antireproductive effect of a potent LHRH antagonist (Nal-Lys antagonist:antide) during early pregnancy in the rat

Effects of a potent third generation LHRH antagonist [Nal-Lys antagonist:antide] have been observed during the first half of pregnancy in rats. A daily dose of 40 micrograms or above, when administered from day 8 of pregnancy, suppressed serum progesterone levels within 48 h and by day 12 there was complete absence of live fetuses. Lower doses of antide (10-20 micrograms) reduced progesterone levels in circulation but were unable to induce abortion consistently in all treated rats. Administration of 150 or 300 micrograms of antide once on day 8 suppressed the progesterone levels within 24 h. Only a dose of 300 micrograms was effective in completely interfering with gestation by day 12 with no observable live fetuses.     

Effects of low dose oral contraceptives containing norethindrone and ethinyl estradiol on serum levels of progesterone and pituitary gonadotropins

Serum gonadotropin and progesterone levels were studied in longterm (>18 months) patients receiving oral contraceptives containing either 1.0 mg or 0.5 mg norethindrone in combination with 35 μg of ethinyl estradiol. In ten patients treated with 1.0 mg norethindrone and 35 μg ethinyl estradiol, no mid-cycle surges of LH were noted and LH levels never exceeded 225 ng/ml. FSH levels were generally elevated during the first half of the cycle. Serum progesterone concentrations in these patients and in fourteen additional women whose blood was sampled intermittently were generally less than 1 ng/ml, and no characteristic luteal phase elevation of this hormone was detected. Of six patients treated with 0.5 mg norethindrone and 35 μg ethinyl estradiol, five clearly had no mid-cycle surge of LH, and levels of this hormone never exceeded 250 ng/ml. The concentrations of FSH and progesterone in these patients and serum progesterone levels in two additional women whose blood was sampled intermittently were similar to those found in patients treated with 1 mg norethindrone and 35 μ ethinyl estradiol. In the sixth patient, hormonal levels did not follow the same pattern, but they were not characteristic of ovulation. It is concluded that there is no evidence of cyclic fluctuations in FSH, LH and progesterone characteristic of ovulation in patients treated longer than eighteen months with either 1.0 mg or 0.5 mg norethindrone in combination with 35 μg ethinyl estradiol.     

Cyclic administration of an LHRH analogue and of progesterone in risk patients to oral contraceptives

Fifty-five cycles of 9 patients with normogonadotropic ovarian function having risks against oral contraceptives (OCs) and intrauterine devices (IUDs) were treated for contraception with buserelin in a dosage of 300 to 450 micrograms per day i.n. from day 5 to day 26 of the cycles. Additionally, progesterone (P) in a dosage of 75 mg per day was given by intravaginal suppositories from day 20 to day 26 of the cycle followed by a 7-day drug-free interval. Serum levels of LH, FSH and estradiol-17 beta (E2) showed a wide variability. However, most E2 levels were in the early or middle follicular phase range. Mean serum P levels monitored during P replacement were found to be in the secretory phase range. Pattern of menstrual cycles was regular in all patients except one whose menstrual bleedings were already disturbed prior to treatment. This mode of contraception was well accepted, no side effects were observed, no pregnancy occurred. In conclusion, contraception by low-dose intranasal application of buserelin combined with transvaginal P replacement seems to be a useful approach for contraception in patients at risk for both OCs and IUDs.     

Hormonal consequences of missing the pill during the first two days of three consecutive artificial cycles

The hormonal effects of the deliberate omission of a low-dose combined oral contraceptive pill (30 micrograms ethinyl estradiol + 150 micrograms levonorgestrel) during the first two days of three consecutive artificial cycles were studied in 10 women. The plasma levels of estradiol, progesterone, levonorgestrel and--whenever justified--of LH were measured three times weekly (Mondays, Wednesdays and Fridays) throughout a 90-day period, and the ovarian reaction to the prolongation of the pill-free period from 7 to 9 days was assessed. One subject (with a premature LH surge) showed a marked follicular and an inadequate luteal activity in 2 of 3 cycles. The remaining cycles were characterized by a varying degree of follicular activity associated with the absence of any luteal function. None of the subjects exhibited peripheral steroid levels indicating a normal ovulatory cycle. The results are interpreted as suggesting that repeated prolongation of the pill-free period from 7 to 9 days might result in a gradual increase in ovarian activity.