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A survey of different approaches to management of menstrual disturbances in women using injectable contraceptives.

This report summarises a survey of the management of menstrual disturbances occurring during injectable progestogen use (depot-medroxyprogesterone acetate, DMPA, and norethisterone enanthate, NET-EN) by 35 investigators from 20 countries with ongoing experience of these contraceptives. A wide range of approaches are described. The most frequently emphasised aspect of management is thorough pre-treatment counselling with further support and counselling at follow-up visits. Oestrogens in various forms are widely used for the treatment of prolonged, frequent or heavy episodes of bleeding, but nowadays are not usually used for the induction of withdrawal bleeding in women with amenorrhoea. Heavy or "severe" bleeding appears to be very uncommon and figures of 1-2% were frequently mentioned. Anecdotal information suggests that intramuscular doses or longer courses (14-21 days) of oral oestrogen, including the combined pill, are more likely to successfully stop an episode of bleeding than short courses. However, there are no hard data to show that a course of oestrogen treatment has any beneficial effect on long-term bleeding patterns. Nevertheless, temporary cessation of spotting or light bleeding may be sufficiently reassuring to the patient to ensure continued use of the method. There appears to be very little risk associated with the short-term oestrogen regimens currently used. Dilatation and curettage is almost never necessary to stop an episode of bleeding, but may occasionally be recommended for diagnostic reasons. It is clear that the bleeding disturbances associated with DMPA and NET-EN use are poorly understood and that urgent research is necessary to clarify pathophysiological mechanisms and improve management.

Amenorrhea↗

Comparison of contraceptive acceptability of levonorgestrel and ethinyl oestradiol administered in one three-phasic (Trionetta) and one monophasic (Neovletta) version.

In a Swedish multicenter study, a total number of 835 women completed a total of 6472 treatment cycles. Half of them were allotted at random to use the monophasic oral contraceptive Neovletta, also known as Microgynon 30 (30 micrograms ethinyl oestradiol + 150 micrograms levonorgestrel in each tablet). The second half was allotted to Trionetta, also known as Triquilar, Trigynon and Logynon (6 tablets with 30 micrograms ethinyl oestradiol + 50 micrograms levonorgestrel, 5 tablets with 40 micrograms ethinyl oestradiol + 75 micrograms levonorgestrel and 10 tablets with 30 micrograms ethinyl oestradiol + 125 micrograms levonorgestrel). The latter version was also present in a 28-day version containing in addition 7 "placebo" tablets to be used in the otherwise tablet-free interval. The contraceptive reliability was excellent although one pregnancy occurred in the three-phase version. It could be attributed to patient failure. In all aspects of bleeding control, the three-phasic pill proved to be superior to the reference monophasic preparation. The extreme low incidence of missed withdrawal bleeding and stability already during the first months of use are noteworthy features. For both preparations, continuation rate was at six months of use about 85% and at 12 months it was a similar figure. The most common reason for withdrawal was bleeding, about 5% each for both preparation. No serious side-effects were reported. The study clearly indicates that the three-phasic version is a major improvement in spite of a considerably decreased total dose of the gestagen.

Clinical Trials as Topic↗

A comparison of Norinyl and Brevicon in three sites in Sri Lanka.

A set of 3 four-cell randomized, blind clinical trials was carried out in Sri Lanka to evaluate the impact of vitamin supplements and different oral contraceptive formulations. This paper concentrates on the comparisons of oral contraceptives. There seems to be no important difference between Norinyl, a standard-dose oral contraceptive, and Brevicon of a lower estrogen dosage--in either continuation or side effects. Continuation at one site was higher among Norinyl users, but several factors led us to the belief that this difference was due to differences in field worker performance rather than to the pharmacological properties of the drugs. Some differences in side effects were observable along predictable lines; breakthrough bleeding was more common among Brevicon users than Norinyl users, and most other side effects were more frequent among Norinyl users, although these latter differences were quite small, and there were several exceptions.

Adolescent↗

Vaginal colonization of Escherichia coli and its relation to contraceptive methods.

The prevalence rate of vaginal colonization with E. coli was studied prospectively among 495 healthy premenopausal women, and factors associated with vaginal carriage of E. coli were examined. Vaginal colonization with E. coli was found in 12% of women, and was significantly correlated with phase of the menstrual cycle (p less than 0.05), prior use of antibiotics (p less than 0.05), current genital complaints (p less than 0.05), history of previous urinary tract infection (p less than 0.001), and use of diaphragm or cervical cap for contraception (p less than 0.005). The high prevalence rate among diaphragm or cervical cap users remained significant when other confounding factors were kept constant (p less than 0.05). This observation may explain the association of diaphragm use and urinary tract infection demonstrated in previous epidemiologic studies and confirmed in the present study (p less than 0.05).

Adult↗

Oral contraceptive steroids do not promote the development or growth of prolactinomas.

Seventy women with prolactinomas, age 19-38 years, were studied in order to evaluate a possible relationship between the use of steroidal oral contraceptives (o.c.) and the development of prolactin-producing adenomas. Sixty-seven patients were admitted for investigation because of menstrual bleeding disturbances and three patients because of galactorrhea. Forty-three patients (61%) had used o.c. Thirty-six out of forty-three women (83%) experienced their menstrual disturbances and/or galactorrhea when using o.c. or immediately after discontinuing the pill. Patients who had used o.c. had shorter duration of symptoms, lower S-prolactin levels and less pronounced enlargement of the sella turcica. These tendencies indicate that o.c. lead to an earlier manifestation of clinically latent prolactin-producing tumours. With or without previous o.c., the patients showed a low total fertility rate, indicating a notably long, clinically undiagnosed period of disease. The accumulated usage of o.c. by the women with prolactinomas was not higher than among the total female population of the same age in Sweden. Furthermore, patients on o.c. for several years did not show a more advanced form of the disease than women who had not taken the pill. Thus, the present study provides no support for the hypothesis that o.c. promote the growth of prolactin-producing pituitary adenomas.

Adenoma↗

Changes of plasminogen activator in human uterine tissue induced by intrauterine contraceptive devices.

Potassium thiocyanate-extractable uterine plasminogen activator activity was determined to be highest in the endometrium surrounding intrauterine devices (IUDs). Such activity was significantly higher than that encountered in control endometrium or in the endometrium remote to IUDs. As in control cases, extracted endometrial activity fluctuated during the intermenstrual ovarian cycle. It was highest in the pre- or periovulation part of the cycle, and it rose again prior to menstruation. These peaks of activity seem to correspond to times in the cycle when metrorrhagia and abnormal menstruation are usually encountered. Possible implications of the myometrial and endometrial patterns of plasminogen activator in control and IUD-exposed uterine tissue are discussed.

Endometrium↗

Contraception with progestagens in systemic lupus erythematosus.

To test the efficacy and tolerance of progestagens as contraceptives in systemic lupus erythematosus (SLE), 200 mg IM norethisterone enanthate was administered to 10 patients, 0.03 mg/day oral levonorgestrel to 15 patients and they were compared with 18 control patients. There were 4 episodes of active SLE in 48 patient-months on norethisterone enantate and 6 episodes in 122 patient-months on levonorgestrel as compared with 9 episodes of active disease in 298 control patient-months (p = ns). There were no pregnancies and intermenstrual bleeding led to discontinuation of medication in 30% of patients. Progestagens may be an alternative contraceptive method in SLE.

Adult↗

Phase IV study of the injection Norigest in Pakistan.

A field study of the injectable contraceptive, norethisterone enanthate (NET-EN), was conducted in family planning clinics in Sind and Punjab provinces of Pakistan, to determine the acceptability and feasibility of providing NET-EN in government family planning clinics staffed by Family Welfare Visitors (FWVs). A total of 2147 women were recruited to the study, of whom approximately three-fourths had never previously used contraception. The overall discontinuation rate at one year was 78 per 100 women; the most common reason for discontinuation was bleeding disturbances, including amenorrhea, although returning to the clinic too late for an injection also accounted for a substantial proportion of the discontinuations. Given adequate training, FWVs were shown to be capable of providing NET-EN in family planning clinics, including managing the bleeding disturbances common with this method of contraception. No pregnancies were reported, demonstrating that the method is highly effective when used in a usual family planning clinic situation.

Adolescent↗

Effect of norethisterone enanthate on the blood count and endometrial histology of Indian women.

Endometrial histology and the haematological indices were studied in women receiving 200 mg of norethisterone enanthate (NET-EN) at 60-day intervals for 24 months as a method of contraception. Significant elevations occurred in the haemoglobin concentration and red blood cell counts during one year of therapy, while eosinophil counts showed a transient increase at 4 months of trial. The changes in the haematological indices seem to be due to stimulation of the erythropoietic system by NET-EN and may also be attributable to diminished blood loss due to amenorrhoea during the course of therapy. The endometrial histology revealed proliferative glands at 2 months which turned quiescent at 6-12 months of NET-EN therapy. Long-term use of 18 months showed atrophic changes with few glands, narrow lumina and stromal oedema.

Blood Cells↗

IUD insertion following induced abortion.

In a multicenter survey, women who received an IUD immediately after abortion were compared with abortion patients who started using oral contraception. Additionally, women receiving a Nova T were compared with women receiving a Multiload 250. Follow-up data were gathered after 6 weeks. Pain was a common phenomenon post-abortum. In the study group of IUD users, complaints about pain were not more frequent than among controls, but if pain was experienced, it was more intense and of longer duration among IUD users. Bleeding immediately following the induced abortion was less frequent among IUD users, but if bleeding occurred, it tended to last longer. The first menstrual period after the induced abortion was heavier and more painful among IUD users. Expulsion of the IUD occurred in 10 cases (3.3%), all of them with the Nova T, none with Multiload. The study did not generate evidence for an increased risk of PID in women receiving an IUD after an induced abortion.

Abortion, Induced↗

Interaction of anticonvulsants and oral contraceptives in epileptic adolescents.

Oral contraceptives are in widespread use, and are commonly prescribed for contraception in patients taking other medications. An example of this is the concomitant use of oral contraceptives and anticonvulsants in epileptic patients. This combination creates a potential for drug interactions which may alter the efficacy of both medications. An apparent interaction between oral contraceptives and anticonvulsants was observed in this study of epileptic adolescent females. This interaction was evidenced by menstrual irregularities which occurred in 65% (7 of 11) of adolescents on both medications concomitantly. The frequency of irregularity was significantly higher in these adolescents when compared to adolescents on either medication alone. Irregularities appeared to be alleviated by increasing the strength of the oral contraceptive, and although a concern, the increased dosage did not affect seizure control.

Adolescent↗

Hormonal contraception in diabetic women: acceptability and influence on diabetes control and ovarian function of a nonalkylated estrogen/progestogen compound.

The clinical acceptability and the influence on diabetes control were investigated in 50 women with insulin-dependent diabetes mellitus (IDDM) during intake of a combined nonalkylated estrogen/progestogen compound (4 mg 17-beta estradiol, 2 mg estriol and 1 mg norethindrone) for one year. In 6 IDDM women, the influence of the hormonal treatment on diabetes control and on ovarian function was investigated by measuring the concentration of glycosylated hemoglobin (Hb-Alc), fasting plasma glucose, serum estradiol, serum estrone, serum progesterone and sex hormone binding globulin (SHBG) capacity. No pregnancy occurred during the study and the overall continuation rate of 60% compare well with the continuation rate normally found in non-diabetic women after administration of conventional type oral contraceptives. No difficulties with diabetes control was registered and no significant changes in insulin requirements, 24-h urinary glucose excretion nd Hb-Alc were found. Ovulation was inhibited during the hormonal intake as judged by serum progesterone measurements. Serum estrone increased (p less than 0.05), but this had no influence on SHBG capacity, indicating that the estrogen/androgen balance was unchanged during treatment.

Adult↗

Post-coital contraception by estrogen/progestagen combination or IUD insertion.

Five-hundred-thirty-eight patients received a complete follow-up to the first menses after post-coital contraception (PCC). Hormonal contraception (pill) was used in 436 women and mechanical contraception (IUD) was used in 102 women. No pregnancies were observed in the IUD group, while 8 pregnancies were found in the hormonal group. A comparative evaluation of the effectiveness and side effects of the two methods was made. The usefulness of PCC after an unprotected intercourse in order to avoid a pregnancy is confirmed.

Adolescent↗

The effect of vaginal administration of low-dose oral contraceptive tablets on human ovulation.

The effect of vaginal administration of a low dose combined oral contraceptive pill containing 0.15 mg levonorgestrel and 0.03 mg ethinyl oestradiol was studied in twenty women for a total of 58 cycles. Ovulation was suppressed in all treatment cycles in women receiving two pills daily. Failure of suppression of ovulation occurred in four out of 26 treatment cycles in women receiving one pill daily. Only seven women complained of side effects; most of the side effects were mild and disappeared gradually within the first treatment cycle. Intermenstrual spotting was present in only one case receiving one pill daily. It is concluded that vaginal administration of low dose combined pills has a good ovulation suppression effect with minimal side effects and with good cycle control.

Administration, Topical↗

Effective contraception with the levonorgestrel-releasing intrauterine device: 12-month report of a European multicenter study.

The use-effectiveness of an intrauterine contraceptive device releasing 20 mcg of levonorgestrel daily (Lng-IUD), and of a Nova T copper-releasing IUD, were studied in a randomized, comparative multicenter trial. The Lng-IUD was inserted in 1821, and the Nova T in 937 women. The 12-month net pregnancy rate with the Lng-IUD (0.1 per hundred women) was significantly lower than that with the Nova T (0.9 per hundred). Removal rates for menstrual problems and/or pain were similar for the two methods (net rates 7.5 and 8.7, respectively). The 12-month continuation rates were 82.2 for the Nova T and 79.7 for the Lng-IUD. The reduction of the bleeding led to oligomenorrhea and amenorrhea in users of the Lng-IUD; the removal rate for these reasons was 1.4. The removal rate for hormonal side effects with the Lng-IUD was 2.4. Blood hemoglobin concentrations increased among users of the Lng-IUD and decreased among users of the Nova T. The results show that the Lng-IUD was a highly effective contraceptive method which reduced menstrual bleeding. It is a promising alternative for women desiring a highly effective method for long-term use.

Adult↗

Postponement of withdrawal bleeding in women using low-dose combined oral contraceptives.

Postponement of menses is widely practised by women using oral contraceptives. One-hundred volunteers, consisting of three groups of women, each group using a different extensively used contraceptive regimen, were tested and compared. The test period consisted mainly of a double (monophasics) or extended (triphasics) pill cycle without a tablet-free interval. Based on daily records of vaginal bleedings as well as on the results of a questionnaire, it could be concluded that postponement of the withdrawal bleeding for twenty extra days was generally effective; the occurrence of the bleedings was related to the duration of postponement of menses and to the contraceptive regimen that was used. However, the introduction of a seven-week cycle pill is not yet a promising alternative since the majority of the volunteers preferred the inconvenience of a monthly withdrawal bleeding.

Adult↗

Two years of intrauterine contraception with levonorgestrel and with copper: a randomized comparison of the TCu 380Ag and levonorgestrel 20 mcg/day devices.

IUDs releasing 20 mcg/day of levonorgestrel (LNg20) were in randomized trial together with the Copper T, model TCu 380Ag, in seven centers involving 2244 women. Two-year (25 months) gross cumulative pregnancy rates were 0.2 +/- 0.2 and 0.9 +/- 0.3 for the levonorgestrel and copper releasing devices, respectively (P greater than 0.05). There were no ectopic pregnancies in more than 1600 woman-years of use of each device. Removal rates for bleeding and/or pain or for medical reasons other than menstrual problems did not differ significantly between devices. Oligomenorrhea or amenorrhea prompted 10.7 per hundred (gross rate, 8.4 net rate) women using the LNg 20 IUD to request removal in the two-year period, significantly above the 0.2 per hundred rate among women with the Copper IUD (P less than 0.001). At the end of two years an estimated 59.4 per 100 women were continuing use of the LNg 20 IUD, and 67.5 per 100 (P less than 0.001) with the TCu 380Ag. This difference is almost wholly ascribable to a marked reduction in bleeding episodes and days among women using the LNg 20 device with concomitant removal of device. Hemoglobin rose an average of 0.5 g/dl (P less than 0.001) for this group whereas women using the TCu 380Ag experienced a decline of 0.2 g/dl compared with baseline values (P less than 0.001).

Adolescent↗

The role of prostaglandins and allied substances in uterine haemostasis.

This review addresses itself to summarizing the more recent studies published on the bioconversion of arachidonic acid in the human endo- and myometrium during the normal menstrual cycle and in women with increased menstrual blood loss. The data indicate an increased ability of the endo- and myometrium from women with menorrhagia to produce prostaglandins with vasodilator and platelet anti-aggregatory properties, viz., prostacyclin and prostaglandin E2. The data on prostaglandin production in endometria of IUD wearers is reviewed and discussed in relation to present knowledge on morphological findings in IUD-influenced endometrium.

Female↗