A double-blind comparison of the efficacy and acceptability of Femodene and Microgynon-30.

The efficacy, cycle-control and tolerance of Microgynon-30, a widely prescribed levonorgestrel containing oral contraceptive, and Femodene, a new oral-contraceptive containing gestodene, were compared in a randomised, double-blind study involving 456 healthy women over a 6 month period. 229 women were allocated to receive Femodene and 227 received Microgynon-30. No differences between the groups in terms of obstetric and gynaecological history, previous contraceptive history, smoking habits, blood-pressure or body weight at admission were observed. No pregnancies were reported in either group, despite tablet-taking errors recorded in 6.3% of the Femodene group and 7.6% of the Microgynon-30 group. Both oral contraceptives were compared in terms of cycle length, intensity of the withdrawal bleed and side effects. Cycle-control was similar in the two groups. However, significantly fewer subjects reported breakthrough bleeding (with or without spotting) in the Femodene group (18% of patients) compared with the Microgynon-30 group (26% of patients). The incidence of absent withdrawal bleeds was 1% or less in both groups and no significant effects on body weight or blood pressure were observed.

Contraception and lactation.

PIP: Lactation's contraceptive effect cannot be relied upon for more than 6 weeks postpartum, and ovulation often occurs in advance of the 1st postpartum menstrual period. Although breastfeeding mothers should adopt a contraceptive method, care must be taken to select a method that will not adversely affect the production and composition of breast milk. Of greatest concern is the effect of synthetic hormones transmitted via breast milk on the developing infant. Possible alternatives are the Billings ovulation detection natural family planning method, diaphragms and caps, IUDs, and sexual sterilization. While combined oral contraceptives (OCs) are contraindicated because of their harmful effects on the fat and protein composition of breast milk and on milk production, the progestogen-only OC does not appear to interfere with the quality of breast milk and less than 0.1% of the progestogen passes on to the infant. Depo-Provera, and other injectable progestogens, appear to be appropriate for breastfeeding women, although the 1st injection should be postponed until 6 weeks postpartum to reduce the likelihood of heavy bleeding. Under investigation is a nasal spray containing buserelin, a luteinizing hormone-releasing hormone agonist, that shows promise as a reliable, acceptable, and easily administered nonsteroidal contraceptive that does not interfere with lactation. A biodegradable buserelin implant, which would last as least 3 months, also is being developed and would be especially useful in developing countries where storage of a nasal spray might be problematic.^ieng

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.

PIP: The effect of deliberate omission of a phased formulation pill, Trinordiol (ethinyl estradiol 30 microgram + levonorgestrel 50 microgram: 6 tablets; ethinyl estradiol 40 microgram + levonorgestrel 75 microgram: 5 tablets; ethinyl estradiol 30 microgram + levonorgestrel 125 microgram: 10 tablets) or a low-dose, combined, oral contraceptive pill, Microgynon (ethinyl estradiol 30 microgram + levonorgestrel 150 microgram: 21 tablets) on the hypothalamo-pituitary-ovarian axis were studied. 36 women were recruited to the study and divided equally between the 2 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 1st 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 3rd week of pill treatment. 5 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, but this level of follicular activity was maintained in only 3 of these women in the 7 "pill-free" days. None of the women taking Microgynon had levels of E2 above 500 pmol/l whilst taking the pills and only 1 patient achieved this degree of follicular activity after stopping the tablets. 1 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 1st 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.

The functional competence of human spermatozoa recovered after vasectomy.

Progressively motile spermatozoa were present in 42/47 (89%) of post-vasectomy specimens, and in 16 of 24 samples (66%) demonstrable fertilizing potential could be detected in the zona-free hamster egg assay. The mean +/- s.e.m. post-vasectomy penetration rate of 20.6 +/- 6.0% was, however, significantly lower (P less than 0.001) than the pre-vasectomy value of 49.7 +/- 6.4%. After vasectomy the concentration of motile spermatozoa in the ejaculates declined in a manner that was significantly correlated with the post-operative time interval. The spermatozoa also lost their potential for fertilization, although functionally competent spermatozoa were still being recovered from ejaculates produced 8 days after vasectomy. These results emphasize the ability of human spermatozoa to retain some residual fertilizing potential when stored at core body temperature in sites distal to the epididymis, and suggest a role for functional tests in the management of the vasectomized male.

Antipyrine elimination in saliva after low-dose combined or progestogen-only oral contraceptive steroids.

1 A 'low-dose' combined oral contraceptive steroid (OCS) preparation containing 30 microgram ethinylo-estradiol and 150 microgram levonorgestrel was found to reduce significantly antipyrine clearance in a group of women acting as their own controls. 2 An OCS preparation containing only a progestogen (75 microgram norgestrel) did not reduce antipyrine clearance in a second group of women. 3 The evidence suggesting that the oestrogen component of combined OCS preparations could be responsible for the reduction in antipyrine clearance is discussed.

PIP: This study investigates the ability of a single preparation of either the low-dose combined or progestogen-only type of oral contraceptives (OCs) to alter antipyrine elimination in 2 groups of women. 6 patients aged 22-28 were given a low-dose combined OC preparation containing 30 mcg ethinyl estradiol and 150 mcg levonorgestrel; 12 patients aged 18-41 were given a preparation containing only a progestogen, 75 mcg norgestrel. Antipyrine elimination kinetics was setermined during the menstrual cycle, and at 11 weeks for the 1st group, and at between 11-14 weeks for the 2nd group, in saliva samples. There was a significant reduction of 29% in antipyrine clearance in the 1st group, and no significant change in antipyrine elimination in the 2nd group. These results are in agreement with previous published results; it is possible that the estrogen component of combined OC preparations could be responsible for the reduction in antipyrine clearance. If it is confirmed that progestogen-only OCs are without effect on antipyrine elimination, then it does imply that the concern that the elimination of any drug which is metabolized by liver microsomal enzymes will be impaired when the drug is administered with an OC is not applicable to progestogen-only preparations.

The effects of sterilisation: a comparison of sterilised women with the wives of vasectomised men.

In a follow-up study, women sterilised by tubal diathermy were compared with a matched group of wives of vasectomised men. Semi-structured interviews were given to a random sample drawn from a representative population. The couples were young with small families and did not have a high proportion of unplanned pregnancies or terminations. They had previously used contraception, mainly the pill or sheath. Most couples were entirely satisfied with the operation. Both groups showed an increase in pre-menstrual symptoms but there was only slight evidence that menstrual loss was affected by female sterilisation. The vasectomy couples had a higher frequency of sexual intercourse, few sexual problems and tended to have more satisfactory marriages. They had had more discussion of their decision to have the operation and the implications of counselling are considered.

Oral contraception.

PIP: Despite the recent publicity given to studies pointing out the negative side effects associated with the use of oral contraceptives, the pill is still the most common form of contraceptive used in Great Britain and constitutes the form of contraception for many women. Some of the negative effects currently receiving wide publicity, no longer represent a serious threat for the pill user; many of these effects have been negated or ameliorated by modifying the composition of the pills. In combined pills the estrogen content has been reduced from 150ug to 20-35ug. In the 2 major studies linking oral contraceptives with the development of cardiovascular disease most of the women in the studied population had taken pills containing 50-100ug of estrogen. Given the wide choice of pills currently available, many of the negative effects, such as nausea and pain, cna be ameliorated by choosing a more appropriate oral contraceptive for the specific patient. Other side effects such as headaches and poor cycle control can be treated by regimen modification. Although there is a relationship between pill use and hypertension, pills containing levonorgestrel in combination with 30ug of ethinyloestradiol have only a slight effect on blood pressure. Lactation is not reduced for women who take progestogen only pills. Fertility is successfully restored in almost all women shortly after they stop using the pill. Drug interaction failures can be avoided in many cases by prescribing pills containing 50ug of estrogen for women taking other drugs. In order to obtain immediate effectiveness, the combined pill can be started on the 1st day of the period instead of waiting until the 5th day.^ieng

Tricycle pill regime.

PIP: A study was undertaken among 202 volunteers to determine whether the number of menstrual periods/year could be reduced to 4 by continuous administration of the oral contraceptive Minilyn for 84 days followed by 6 free days over a year and, if so, whether such a change would be acceptable. Tricycle administration was associated with side effects of spotting and breakthrough bleeding (in 24% of the patients in the 1st cycle, 4% in the 4th), weight gain (46%), breast discomfort (13%), headache (11%), dysmenorrhea (9%), and the Of the women, 82% approved of the reduction in number of menstrual periods, and 91% of the 53% who completed the trial refused to revert to a monthly regimen (66% of the patients who withdrew from the trial liked the idea of less frequent menstrual periods). Despite the self-selected nature of the women studied, there is evidence that women would appreciate the opportunity to manipulate the frequency of their menstrual periods. The optimum dosage of oral contraceptives to attain this condition has yet to be determined, and the dosage of estrogen in particular may be significantly reduced. If such a regimen proves attractive, attention might be focused on the development of nonestrogenic drugs for contraceptive purposes. The side effect of amenorrhea may even be an attraction to the use of such drugs.^ieng

Acceptability of an oral contraceptive that reduces the frequency of menstruation: the tri-cycle pill regimen.

The frequency of menstruation was reduced to once every three months in 196 women by the continuous administration of the oral contraceptive pill, Minilyn, for 84 days (tri-cycle regimen). No pregnancies occurred. One hundred and sixty-one women (82%) welcomed the reduction in the number of periods with the associated freedom from menstrual and premenstrual symptoms, and many found the tri-cycle regimen easier to follow. Weight gain of more than 2 kg, irregular cycle control, especially in the first three months, breast tenderness, and headaches were the main side effects. Menstrual loss was unchanged or reduced in all but seven women. The doctors and nurses on the clinic staff were less enthusiastic about this regimen than the volunteers themselves.

Intrauterine deposition of calcium on copper-bearing intrauterine contraceptive devices.

Copper-bearing intrauterine contraceptive devices (IUDs) removed after various times in utero were examined by scanning electron microscopy and x-ray microanalysis of the elements present. As time in utero increased these devices became increasingly calcified. This calcification may limit the release of copper from the devices and decrease the specific contraceptive effectiveness of copper over an enert plastic device. Conversely, any teratogenic effects attributable to the copper may decrease with time in utero and depend on the extent of calcification. Even though the amount of copper in the device is not significantly diminished after two years, devices should not remain in situ for over two years because calcium accumulation probably prevents further diffusion of copper. Calcification can begin as early as six months after insertion. Consequently a careful review of the amount of time a copper-containing IUD should be left in situ should be undertaken.

Phytohemagglutin-induced lymphocyte transformation in oral contraceptive users.

Phytohemagglutin (PHA)-induced lymphocyte transformation (PILT) was determined in 217 women taking oral contraceptives and 203 control women by means of the uptake of 3H-thymidine into DNA of lymphocytes cultured in heterologous serum. Depressed PILT responses were observed in oral contraceptive users as compared with age-matched controls, and the magnitude of depression correlated with the duration of oral contraception and was inversely related to the clinical progestagenic potency of the component steroids. An additional group of 21 women, tested within 1 year (mean 3 months) of cessation of oral contraception, showed persistent depression of PILT responses. Suppression of lymphocyte transformation in autologous as compared with homologous, normal serum suggests that serum inhibitory factors amy be important. We found no evidence for a direct suppressive in vitro effect of synthetic estrogens and gestagens. The prevalence of autoantibodies in oral contraceptive users was similar to that in control subjects.

Detection of breast disease in a family planning association clinic.

The incidence and prevalence of disorders of the breast have been assessed in 13,456 women examined annually at a family planning clinic over 5 years. Screening for disorders of the breast was by clinical examination alone and abnormalities were detected in 1 of every 58 women attending the clinic and these were referred for hospital opinion: biopsy was required in 1 in 114. Only 12 cancers of the breast were detected and all of these in women over 35 years. It is suggested that the usual policy of examining the breasts of women taking oral contraceptive preparations should be restricted to those over 40 years.