Effects of (15S)-15-methyl prostaglandin F2 methyl ester and estrogens upon the corpus luteum and conceptus of the rhesus monkey

The corpus luteum inhibiting properties of eighteen 15-methyl prostaglandin analogs were determined in the rhesus monkey during concomitant stimulation of the corpus luteum with chorionic gonadotropin. The methyl ester of (15S)-15-methyl PGF_2^α (15M-PGF_2^α, 12.5 mg/monkey) lowered serum progesterone to 12% of pretreatment values within 24 hours, however progesterone returned to normal limits within 48 hours. Elongation of the top side-chain by two carbons (2a,2b-dihomo-15M-PGF_2^α methyl ester, 13 mg/monkey), substitution of a hydroxymethyl group at carbon 1 (2-decarboxy-2-hydroxymethyl-15M-PGF_2^α, 12 mg/monkey), or the formation of the carbon 1 amide (15M-PGF_2^α amide, 12.5 mg/monkey) improved the inhibitory activity of 15M-PGF_2^α; serum progesterone for these 3 analogs was depressed to 15–30% of pretreatment levels within 24 hours, and did not return to control values. Luteal function was not inhibited (12 or more mg/monkey) when the 15-methyl group was placed in the R configuration, the top side chain was shortened by two carbons, an amino group was substituted for carbon 1, the 5-oxa modification was added, or the 1,9-lactone was formed. Some other modifications of 15M-PGF_2^α were also inactive, although not all were tested at equivalent doses: 2,2-difluoro; 4,5-cis-didehydro; 9,11-dideoxy-9α,11α-dichloro; 11-deoxy; 17-phenyl; 1,15-lactone; and the p-benzamidophenyl ester of 2a,2b-dihomo-15M-PGF_2^α. (15S)-15-Methyl PGE₂ methyl ester (1 mg/monkey) depressed serum progesterone concentrations to 42% of pretreatment values within 24 hours; 2a,2b-dihomo-11-deoxy-(15S)-15-methyl PGE₂ methyl ester was inactive (5 mg/monkey). A corpus luteum inhibiting action of certain 15-methyl prostaglandins can be demonstrated in the rhesus monkey.     

Treatment with a single vaginal suppository containing 15-methyl PGF2α methyl ester at expected time of menstruation

Termination of early pregnancy, by vaginal administration of prostaglandin analogues, one to three weeks after the first missed menstrual period, has advantages and disadvantages in comparison with vacuum aspiration. Some of these may be reduced if the patient is treated earlier. In the present study the effect and safety of one vaginal administration of 2.5 to 3 mg 15-methyl-PGF_2α methyl ester around the expected time of menstruation was evaluated in 16 women exposed to the risk of pregnancy.The overall number of treatment cycles was 35 and pregnancy was confirmed by plasma β-HCG in eight. The treatment resulted in bleeding in all the pregnant cycles while in the nonpregnant ones it only provoked spotting and bleeding did not begin until the expected time of menstruation. Treatment with 2.5 mg 15-methyl-PGF_2α methyl ester resulted in complete abortion in one of three women. If the dose was increased to 3 mg all five treated women aborted. In nonpregnant patients no changes in the levels of estradiol-17β or progesterone at any time during the 24-hour observation period were found. Serum cortisol and prolactin but not TSH levels started to increase two hours after the start of treatment and reached a maximum after five hours. The increase coincided with the onset of uterine pain.Ovulatory cycles as judged from basal body temperature occurred in the first menstrual cycle following treatment in all nonpregnant patients. Although possible to use as a “once a month treatment” it seems preferable since the dose is the same, to postpone treatment until menstruation is delayed for a week or more.     

Effect of estrogen and progesterone treatment on the depressor response to prostaglandin E2 in ovariectomized women

The effect of exogenous estrogen and progesterone on the response of the systemic arterial pressure to prostaglandin E₂ (PGE₂) was studied in 15 ovariectomized women. All experiments were performed on the 7th postoperative day. Arterial blood pressure was measured in all women in supine position at one minute intervals by an automatic recorder. PGE₂ infused intravenously in all subjects for 10 minutes. Ten of the women who were given intramuscular injections of either estradiol benzoate (10 mg) or inert vechicle 60–65 hours before the experiment, showed a significant decline in both systolic and diastolic blood pressure during the PGE₂ infusion. In contrast, the remaining of the women who were injected with progesterone intramuscularly also 60–65 hours before the experiment, did not present any significant alterations in blood pressure during or after the infusion of PGE₂. These results suggest that, in ovariectomized women, progesterone treatment prevents the depressor response to PGE₂. This may be due to increased inactivation of PGE₂ by various tissues.     

Preoperative dilatation of the cervix by single vaginal administration of 15-methyl-PGF2α-methyl ester

Two different vaginal suppositories have been developed suitable for one single treatment for preoperative dilatation of the cervix prior to vacuum aspiration in late first trimester abortion. The study included 60 patients equally distributed in one control group (Group I) where vacuum aspiration was performed without pretreatment; one group (Group II) where the patients obtained 2.0 mg 15-methyl-PGF_2α-methyl ester in a rapid releasing base six hours prior to operation and one group (Group III) where the prostaglandin dose was increased to 2.5 mg 15-methyl-PGF_2α-methyl ester and a more slow releasing base was used and the operation performed after 12 hours. The mean cervical dilatation at operation was in Group II 9 mm and in Group III 11 mm in comparison with 4.8 mm in the control group. The bleeding at the operation was also significantly reduced.     

Inhibition of the monkey corpus luteum with 15-methyl prostaglandins

The corpus luteum inhibiting properties of eighteen 15-methyl prostaglandin analogs were determined in the rhesus monkey during concomitant stimulation of the corpus luteum with chorionic gonadotropin. The methyl ester of (15S)-15-methyl PGF_2^α (15M-PGF_2^α, 12.5 mg/monkey) lowered serum progesterone to 12% of pretreatment values within 24 hours, however progesterone returned to normal limits within 48 hours. Elongation of the top side-chain by two carbons (2a,2b-dihomo-15M-PGF_2^α methyl ester, 13 mg/monkey), substitution of a hydroxymethyl group at carbon 1 (2-decarboxy-2-hydroxymethyl-15M-PGF_2^α, 12 mg/monkey), or the formation of the carbon 1 amide (15M-PGF_2^α amide, 12.5 mg/monkey) improved the inhibitory activity of 15M-PGF_2^α; serum progesterone for these 3 analogs was depressed to 15–30% of pretreatment levels within 24 hours, and did not return to control values. Luteal function was not inhibited (12 or more mg/monkey) when the 15-methyl group was placed in the R configuration, the top side chain was shortened by two carbons, an amino group was substituted for carbon 1, the 5-oxa modification was added, or the 1,9-lactone was formed. Some other modifications of 15M-PGF_2^α were also inactive, although not all were tested at equivalent doses: 2,2-difluoro; 4,5-cis-didehydro; 9,11-dideoxy-9α,11α-dichloro; 11-deoxy; 17-phenyl; 1,15-lactone; and the p-benzamidophenyl ester of 2a,2b-dihomo-15M-PGF_2^α. (15S)-15-Methyl PGE₂ methyl ester (1 mg/monkey) depressed serum progesterone concentrations to 42% of pretreatment values within 24 hours; 2a,2b-dihomo-11-deoxy-(15S)-15-methyl PGE₂ methyl ester was inactive (5 mg/monkey). A corpus luteum inhibiting action of certain 15-methyl prostaglandins can be demonstrated in the rhesus monkey.     

Cervical dilatation with prostaglandin analogues prior to vaginal termination of first trimester pregnancy in nulliparous patients

Dilatation of the cervix with prostaglandin analogues prior to vaginal termination of pregnancy was attempted in 125 nulliparous women in the first trimester of pregnancy. The patients were divided into five groups (25 in each group) and given a single extra-amniotic dose of one of the following prostaglandin analogues 14–16 hours prior to the evacuation of the uterus by vacuum aspiration. (Group A) 15 (S) 15 methyl PGE₂ (free acid); (Group B) 15 (S) 15 methyl PGE₂ methyl ester; (Group C) 15 (S) 15 methyl PGF_2α (free acid); (Group D) 15 (S) 15 methyl PGF_2α methyl ester and(Group E) a mixture of 15 (S) 15 methyl PGE₂ methyl ester and 15 (S) 15 methyl PGF_2α methyl ester. Evacuation of the uterus without mechanical dilatation of the cervix was possible in 111 (90%) of the patients. In an additional 10 patients (8%) there was some degree of cervical dilatation and further mechanical dilatation could be performed easily. With the combination of 15 (S) 15 methyl PGE₂ methyl ester and 15 (S) 15 methyl PGF_2α methyl ester the incidence of gastrointestinal side effects and pyrexia were considerably reduced.     

Peripheral plasma concentrations of 13,14-dihydro-15-keto-prostaglandin F2α and progesterone around luteolysis and during early pregnancy in the goat

Peripheral plasma concentrations of 13,14-dihdyro-15-keto-prostaglandin F_2α (PGFM) and progesterone were determined during both luteolysis in the oestrous cycle and early pregnancy in four goats. Luteal regression, characterised by decreasing progesterone concentrations, began on day 12 or 13. PGFM concentrations showed a pulsatile pattern around this time, with peak concentrations increasingly markedly as progesterone levels fell and oestrus approached. During early pregnancy progesterone concentrations did not fall after day 12 and no marked elevation of PGFM above basal values of 50–150 pg/ml was detected.     

Effects of PGF2α and PGF2α, 1–15 lactone on the corpus luteum and on early pregnancy in the rhesus monkey

The effects of prostaglandin (PG)F_2α and PGF_2α, 1–15 lactone were compared in luteal phase, non-pregnant and in early pregnant rhesus monkeys. Animals treated with either PG after pretreatment with human chorionic gonadotropin (hCG) had peripheral plasma progesterone concentrations that were not statistically different from those in animals treated with hCG and vehicle. However, menstrual cycle lengths in monkeys treated with PGF_2α, 1–15 lactone were significantly (P <0.02) shorter than those in vehicle treated animals. In the absence of hCG pretreatment, plasma progesterone concentrations were significantly (P <0.008) lower by the second day after the initial treatment with either PGF_2α or PGF_2α, 1–15 lactone than in vehicle treated monkeys. Menstrual cycle lengths in monkeys treated with either PG were significantly (P <0.04) shorter than those in animals treated with vehicle. There were no changes in plasma progesterone concentrations in early pregnant monkeys treated with PGF_2α, and pregnancy was not interrupted. In contrast, plasma progesterone declined and pregnancy was terminated in 5 of 6 early pregnant monkeys treated with PGF_2α, 1–15 lactone. These data indicate that PGF_2α, 1–15 lactone decreases menstrual cycle lengths in non-pregnant rhesus monkeys. More importantly, PGF_2α, 1–15 lactone terminates early pregnancy in the monkey at a dose which is less than an ineffective dose of PGF_2α.     

Induced abortion in the 8–9th week of pregnancy with vaginally administered 15-methyl PGF2α methyl ester

15(S)15-methyl PGF_2α methyl ester was self-administered vaginally to terminate pregnancy in 42 women in the 8–9th week of gestation. Ten patients received a total of 6 mg of the compound over 15 hours (Group I) while the remaining 32 patients received 5.5 mg of the prostaglandin compound during a shorter period of time or 9 hours (Group II). If parts of the conceptus were expelled during treatment, surgical intervention was excluded. All patients were followed closely after treatment with repeated serum HCG assays and clinical examinations. All patients in Group II and eight out of ten patients in Group I aborted following treatment. In 33 of the 42 patients, the serum HCG levels and the clinical course following the expulsion of the conceptus indicated that abortion was complete. Gastro-intestinal side effects were minimal if anti-diarrheic agents were given prophylactically. The incidence of uterine pain was variable but could in most cases be controlled by oral or rectal administration of analgetics. The results of this study suggest that the use of this compound for termination of pregnancy may be safely extended through the 9th week of gestation and in certain cases be an alternative to the normal operative procedure.     

Effect of 15(S)15-methyl-PGF2α-methyl ester vaginal suppositories on circulating hormone levels in early pregnancy

Intravaginal administration of 15-methyl-PGF_2α-methyl ester in the form of suppositories terminated pregnancy in 70 percent of the cases whose last menstrual periods ranged from 35 to 56 days. The use of these suppositories in 49 patients, between 57 to 80 days of gestation, dilated the cervix by 10 mm or more, in one hundred percent of the cases. A decrease in circulating levels of estradiol-17β and progesterone was observed following 15-methyl-PGF_2α administration. The mean estradiol-17β levels declined by about 55.9 percent at 9 hours whereas, the corresponding fall in progesterone was 32.7 percent. This was indicative of a direct action of 15-methyl-PGF_2α on the corpus luteum. The vaginal use of 15-methyl-PGF_2α-methyl ester suppositories thus appears to be a promising method for the termination of early pregnancy and for pre-operative cervical dilatation. The termination of early pregnancy appears to be partly due to the luteolytic effect of 15-methyl-PGF_2α besides stimulating uterine contractions.     

Effect of intravenous infusion of 15-methyl-PGF2α on plasma hormone levels during early pregnancy

Ten pregnant women (7th–8th week of pregnancy) obtained an intravenous infusion of 15-methyl-prostaglandin-F_2α (2.5 μg/min) until clinical signs of abortion occurred or up to 7 hours. Surgical removal of the products of conception was performed 4–7 hours after the start of the infusion. Blood samples were taken prior to and during the infusion and then during the post-abortion period. The plasma levels of both progesterone and estradiol exhibited a significant decrease (p<0.001 and p<0.05, respectively) one hour after the beginning of infusion and remained reduced by approximately 35 and 45 per cent, respectively, during the entire infusion period. A drop in the levels of both steroids was seen after surgical interruption. This was followed by a gradual decrease to non-pregnancy levels. The levels of cortisol increased significantly (p<0.01) by approximately 60 per cent, starting with the second hour of infusion. Following surgical interruption, the levels dropped to pre-infusion values. 17-Hydroxyprogesterone levels increased (p<0.05) above the pretreatment levels by approximately 25 per cent, starting with the third hour of infusion. These levels were not correlated with those of cortisol during the infusion period. Following surgical interruption the plasma levels of 17-hydroxyprogesterone returned to non-pregnancy levels.     

15(S)15-Methyl protaglandin F2α for termination of very early human pregnancy. A comparative study of a single intramuscular injection and vaginal suppositories

The results of a comparative study of the efficacy and acceptability of 15(S)15-methyl prostaglandin F_2α (15-Me-PGF_2α) administered as a single i.m. injection or vaginal suppositories (15-Me-PGF_2α methyl ester) every 3rd hr for termination of very early human pregnancy is reported. The amenorrhoic period varied from 37 to 60 days. (30 cases) received 0.6 mg as a single i.m. injection without any pretreatment. Restrospectively 24 of the 30 women were in fat pregnant and 22 of them aborted. received suppositories (1.0 or 1.5 mg per suppository). In this group all women were pregnant and they all aborted.Symptoms such as pain, bleeding, vomiting and diarrhea started in general earlier in the i.m. group and they were more marked. In the present series the efficacy and acceptability were highest for the vaginal route of administration.     

Uptake of 15N fertilizer in compost-amended soils

Composts are considered low analysis fertilizers because their nitrogen and phosphorus content are around 1% and the organic nitrogen mineralization rate is near 10%. If compost is added to agricultural land at the N requirement of grain crops (40 – 100 kg N ha^–1), application rates approach 40–100 mg ha^–1. Much lower rates may be advisable to avoid rapid accumulation of growth limiting constituents such as heavy metals found in some composts. Combining low amendment rates of composts with sufficient fertilizer to meet crop requirements is an appealing alternative which (a) utilizes composts at lower rates than those needed to supply all the crop N requirement, (b) reduces the amount of inorganic fertilizer applied to soils, and (c) reduces the accumulation of non-nutrient compost constituents in soils. A study was conducted to compare the effects of blends of biosolids compost (C) with ¹⁵N urea(U) or ¹⁵NH4 ¹⁵NO3 (N) fertilizers to fertilizer alone on tall fescue (Festuca arundinacea L.) growth and N uptake. Blends which provided 0, 20, 40 or 60 mg N kg^–1 application rate as compost N and 120, 100, 80 or 60 mg N kg^–1 as fertilizer N, respectively, were added to Sassafras soil (Typic Hapludults). Fescue was grown on the blends in a growth chamber for 98 days. Fescue yields recorded by clippings taken at 23, 46 and 98 days and roots harvested after the 98-day clipping increased with increasing fertilizer level for both NH₄NO₃ and urea and with or without compost. Nitrogen uptake by fescue responded similarly to yield with increases recorded with increasing fertilizer levels with or without compost. Paired comparisons based on cumulative 98-day clippings data showed that yields from blends were equal to yields from fertilizer treatments containing the same percentage of fertilizer as the blends. These data indicated that compost did not provide sufficient plant-available N to increase yields or N uptake. None of the blends equaled 120 mg N kg^–1 fertilizer rate except for 100 mg NH₄NO₃-or urea-N kg^–1 –20 mg compost-N kg^–1blends. The data suggest that biosolids compost blended with fertilizer at a rate of 2–6 mg ha ^–1 did not supply sufficient additional available N to increase yields or N uptake over those of fertilizer alone.     

The effects of danazol mefanamic acid, norethistherone and a progesterone-impragnated coil on endometrial prostaglandin concentrations in women with monorrhagia

The effects of our four medical treatments have been assessed on menstrual blood loss (MBL) and endometrial prostaglandin (PG) concentrations in 30 women with objectively confirmed menorrhagia. Patients were randomly treated with danazol, 200mg daily (n=6), mefanamic acid, 500mg three times daily during menses (n=8), norethisterone, 5mg twice daily from day 15–25 of the cyle (n=8) or a progesterone-impregnated coil releasing 65ug progesterone daily (n=8). Endometrial biopsies were obtained in the mid-luteal phase before and after treatment in 23 cases, and assayed for PG content using radioimmunoassay. Treatment with norethisterone had no effect on either MBL or the concentration of PGs in the endometrium. MBL was significantly reduced after treatment with mefanamic acid (P=0.05, n=6) and the progesterone coil (P0.05, n=6), was reduced in each of 4 cases treated with danazol in whom endometrial biopsies were available. Although there was no consistent change in endometrial PG cocentrations in either the mefamic acid or danazol groups, the lower MBL after insertion of the progesterone coil was associated with a reduced endometrial content of PGE, PGF_2α and “total” PG (6oxo PGF_1α+PGE+PGE_2α)−P=0.05. Wherease the cyclooxygenase inhibitor mefenamic acid is likely to exert its effect on endometrial PGs at the time of menstruation itself, the continous administration of progesterone throught the menstrual cycle could result in both an impairment in estrogen receptor generation leading to reduced estrogen-mediated cyclooxygenase activity, and an increase in endometrial PG metabolism.     

Termination of early gestation with a vaginal polysiloxane device impregnated with (15S) -15 methyl prostaglandin F2a methylester

An investigation of the abortifacient activity of (15S) -15 methyl prostaglandin F2_a methyl ester released from a vaginal polysiloxane device was performed in eleven pregnant women of 49 days gestation or less. Bleeding and contractions were induced in all women, but only seven aborted their pregnancies. Five subjects received a vaginal device impregnated with 3 mg of drug and two aborted fetal tissue. Six women were given a vaginal device containing 5 mg of drug and five aborted fetal tissue. Ten of the patients had significant side effects, nausea, emesis, diarrhea and chills. Six women expelled the device prior to the termination of therapy. This prostaglandin analogue, when administered from a vaginal polysiloxane device in early gestation was an effective abortifacient but was accompanied by systemic side effects and a high incidence of expulsion of the evidence prior to its scheduled removal.     

“Menstrual induction” with sulproston

The PGE₂-analogue Sulproton (16-phenoxy·ω-17,18,19,20-tetranor-PGE₂-mythylsulfonylamide) was administered to 200 medically and gynecologically normal women who were 17±0.4 days beyond their expected menstrual period and who had a positive pregnancy test. The intramuscular impact dose (500 μg repeated after 4 hours) caused an immediate tonic uterine contraction which compromised the estradiol 17β, progesterone and chorionic gonadotropin production within the fetoplacental unit, and thereby allowed the evolution of cyclic uterine activity, cervical dilatation and tissue expulsion.Pregnancy termination was complete in 92% of women, 5.5% required surgical curettage and 2.5% were given a second Sulproston treatment 2–3 weeks after the first to remove retained tissue from the uterus. The medical induction of menstruation was preferred by 83% of the women who had previously experienced surgical termination of pregnancy. Normal menstruation resumed in all women after 36±0.9 days. The majority of 42 women questioned found Sulproston a satisfactory, safe, simple and effective drug regimen for “menstrual induction”.     

Induction of abortion with intra-amniotic or intra-muscular 15(S)-15-methyl-prostaglandin F2α

In order to evaluate the efficacy and acceptability of 15(S)-15-methyl-prostaglandin F_2α (15-me-PGF_2α) for pregnancy termination, we induced 30 abortions with single intra-amniotic injections of 2,5 mg of 15-me-PGF_2α and 25 abortions with intra-muscular 15-me-PGF_2α administered 200 μg initially and 300 μg every third hour until 30 hrs or abortion. Abortion occurred within 30 hrs in 97 % of cases in the intra-amniotic group, with a mean abortion time of 17,6 hrs and in 80 % in the intramuscular group, with a mean abortion time of 15.0 hrs. Neither parity nor gestational age was significantly related to the abortifacient efficacy of 15-me-PGF_2α. No serious complications occurred. Vomiting (83–84 %) and diarrhoea (23–92 %) were the most common complaints. Uterine contractions were more painful if induction was effected with intra-amniotic rather than intramuscular injections. 15-me-PGF_2α appears to be an effective and practicable abortifacient which can be used intra-amniotically or intramuscularly according to the ease of amniocentesis.     

Termination of early pregnancy by a single-dose 3.0 mg 15-methyl PGF2α methyl ester vaginal suppository

The abortifacient effect of a single-dose, long-acting vaginal suppository containing 3.0 mg of 15-methyl PGF_2α methyl ester was investigated in 104 early pregnancies. The pregnancy was terminated in 91 per cent of the cases. The abortion was uncomplicated in 79 patients, while 12 patients experienced prolonged bleeding.In 21 uncomplicated cases, Vabra® curettage done 4 weeks after therapy revealed necrotic residual tissue in 16 patients and nonspecific endometritis in 20 patients. Residual tissue was found in about 50 per cent of the patients curettaged after 1st menstruation, but no residua was found after 2nd menstruation.In patients with prolonged bleeding, substantial amounts of necrotic residual tissue was found in all patients curettaged 4 weeks after therapy. The decline of serum hCG and plasma progesterone levels was significantly slower in these patients as compared with uneventful abortions.     

Effect of in vivo prostaglandin treatment on H-PGF2α uptake in hamster corpora lutea

Pregnant hamsters were administered (SC) prostaglandin or vehicle on the morning of the 4th day of pregnancy. Serum progesterone was significantly depressed (p<.01) at 0.5, 2, and 6 hours after treatment with 100 μg PGF_2α. Serum progesterone levels were unchanged 2 hours and 6 hours after treatment with 100 μg PGF_2β and 2 hours after treatment with 1 mg PGF_2β. Progesterone levels were depressed to less than 1 ng/ml 6 hours after treatment with 1 mg PGF_2β. The specific uptake of ³H-PGF_2α in whole hamster corpora lutea was significantly depressed 2 hours and 6 hours following 100 μg PGF_2α treatment. A 15% depression in specific uptake occurred 0.5 hour post-treatment. Treatment with 100 μg PGF_2β resulted in no change. Administration of 1 mg PGF_2β resulted in depressed ³H-PGF_2α uptake at both 2 and 6 hours post-treatment.Prostacyclin (PGI₂) treatment resulted in no change in either ³H-PGF_2α specific uptake or serum progesterone 2 hours after 100 μg treatment SC. These parameters were both reduced approximately 30% 6 hours post-treatment. Treatment with 6-keto-PGF_1α resulted in a complete lack of measurable ³H-PGF_2α uptake and serum progesterone levels less than 1 ng/ml at both 2 and 6 hours after treatment with 1 mg SC.     

Induction of abortion with intra-amniotic or intra-muscular 15(S)-15-methyl-prostaglandin F2α

In order to evaluate the efficacy and acceptability of 15(S)-15-methyl-prostaglandin F_2α (15-me-PGF_2α) for pregnancy termination, we induced 30 abortions with single intra-amniotic injections of 2,5 mg of 15-me-PGF_2α and 25 abortions with intra-muscular 15-me-PGF_2α administered 200 g initially and 300 g every third hour until 30 hrs or abortion. Abortion occurred within 30 hrs in 97 % of cases in the intra-amniotic group, with a mean abortion time of 17,6 hrs and in 80 % in the intramuscular group, with a mean abortion time of 15.0 hrs. Neither parity nor gestational age was significantly related to the abortifacient efficacy of 15-me-PGF_2α. No serious complications occurred. Vomiting (83–84 %) and diarrhoea (23–92 %) were the most common complaints. Uterine contractions were more painful if induction was effected with intra-amniotic rather than intramuscular injections. 15-me-PGF_2α appears to be an effective and practicable abortifacient which can be used intra-amniotically or intramuscularly according to the ease of amniocentesis.