Term Contraception Research Articles

New approaches for male fertility control: HE6 as an example of a putative target

Reversible contraceptive methods for males are still not available. During the last few years several marketing studies have clearly shown that men and women would welcome a situation where men could assume responsibility for family planning. Schering AG and Organon are currently collaborating to develop a hormonal method for male fertility control based on the combination of etonogestrel as gestagenic component and testosterone undecanoate. To further optimize male contraceptives in terms of improved efficiency, rapid onset, reversibility, fewer side effects and a convenient method of application, a search for innovative non-hormonal approaches was started. During the last few years, numerous proteins were identified which play a specific role in male fertility. These proteins have first to fulfil a set of indication-specific criteria before a drug discovery process can be initiated. The most important criteria for a putative target protein are tissue-selective expression, crucial biological function in fertility, drugable properties and feasibility of assay development for high-throughput-screening and lead optimization. The G-protein-coupled receptor HE6 was selected as target and the above selection criteria were applied. HE6 displays a preferred epididymis-specific expression pattern and belongs to the superfamily of GPCRs, which are well known to be drugable with small molecules. A knockout mouse was generated which revealed an infertility phenotype with the onset occurring 6 weeks after initiation of spermatogenesis at the latest. Surprisingly, no epididymis-specific phenotype was observed. Instead, the reabsorption of testicular fluid along the efferent ducts was strongly affected. No further obvious side effects were observed in male or female mice. This study with HE6 exemplifies how targets for male contraception have to be validated before drug development can start.

Biphasic versus monophasic oral contraceptives for contraception: a Cochrane review.

Side-effects caused by oral contraceptives discourage compliance with and continuation of oral contraceptives. Three approaches have been used to decrease these adverse effects: reduction of steroid dose, development of new steroids, and new formulas and schedules of administration. The third strategy led to the biphasic oral contraceptive pill. We compared biphasic oral contraceptives with monophasic oral contraceptives in terms of efficacy, cycle control and discontinuation due to side-effects. Our a priori hypotheses were: (i) biphasic oral contraceptives are less effective in preventing pregnancy than monophasic oral contraceptives, and (ii) biphasic oral contraceptives cause more side-effects, give poorer cycle control and have lower continuation rates. We searched computerized databases Medline, Embase, Popline and the Cochrane Controlled Trial Register. Additionally, we searched the reference lists of all potentially relevant articles and book chapters. We also contacted the authors of relevant studies and pharmaceutical companies in Europe and the USA. We included randomized controlled trials comparing any biphasic oral contraceptive with any monophasic oral contraceptive when used to prevent pregnancy. We examined the studies found during the various literature searches for possible inclusion and assessed their methodological quality using the Cochrane guidelines. We contacted the authors of all included studies and of possibly randomized studies for supplementary information about the study methods and outcomes. We entered the data in RevMan 3.1, imported the data into RevMan 4.1, and calculated Peto odds ratios for the incidence of intermenstrual bleeding, absence of withdrawal bleeding and study discontinuation due to intermenstrual bleeding. Only one trial of limited quality compared a biphasic and monophasic preparation. This trial examined 533 user cycles of a biphasic pill (norethindrone 500 microg/ethinyl estradiol 35 microg for 10 days, followed by norethindrone 1000 microg/ethinyl estradiol 35 microg for 11 days) and 481 user cycles of a monophasic contraceptive pill (norethindrone acetate 1500 microg/ethinyl estradiol 30 microg daily). The study found no significant differences in intermenstrual bleeding, amenorrhoea and study discontinuation due to intermenstrual bleeding between the biphasic and monophasic oral contraceptive pills. Conclusions are limited by the identification of only one trial, the methodological shortcomings of that trial and the absence of data on accidental pregnancies. However, the trial found no important differences in bleeding patterns between the biphasic and monophasic preparations studied. Since no clear rationale exists for biphasic pills and since extensive evidence is available for monophasic pills, the latter are preferred.

Biphasic versus triphasic oral contraceptives for contraception.

Side effects caused by oral contraceptives discourage compliance with and continuation of oral contraceptives. A suggested disadvantage of biphasic oral contraceptive pills as compared to triphasic oral contraceptive pills is an increase in breakthrough bleeding. We conducted this systematic review to examine this potential disadvantage. To compare biphasic oral contraceptives with triphasic oral contraceptives in terms of efficacy, cycle control, and discontinuation due to side effects. We searched computerized databases MEDLINE, EMBASE, POPLINE and the Cochrane Controlled Trial Register. Additionally we searched the reference lists of potentially relevant articles and book chapters. We also contacted the authors of relevant studies and pharmaceutical companies in Europe and the U.S. We included randomized controlled trial comparing any biphasic oral contraceptive with any triphasic oral contraceptive when used to prevent pregnancy. We examined the studies found during the various literature searches for possible inclusion and assessed their methodological quality using the Cochrane guidelines. We contacted the authors of all included studies and of possibly randomized studies for supplemental information about the study methods and outcomes. We entered the data in RevMan 3.1 and later imported them into RevMan 4.1. We calculated Peto odds ratios for incidence of incidence of discontinuation due to medical reasons, intermenstrual bleeding, absence of withdrawal bleeding, and discontinuation due to intermenstrual bleeding. Only two trials of limited quality met our inclusion criteria. Larranaga (1978) compared two biphasic and one triphasic pills, each containing levonorgestrel and ethinyl estradiol. No important differences emerged, and the frequency of discontinuation due to medical problems was similar with all three pills. Percival Smith (1990) compared a biphasic pill containing norethindrone (Ortho 10/11) with a triphasic pill containing levonorgestrel (Triphasil) and another triphasic pill containing norethindrone (Ortho 7/7/7). The biphasic pill had inferior cycle control compared with the levonorgestrel triphasic pill. The odds ratio of cycles with intermenstrual bleeding was 1.7 (95%CI 1.3-2.2) for the biphasic pill compared with the triphasic levonorgestrel pill. The odds ratio of cycles without withdrawal bleeding was 6.5 (95%CI 3.1-13). In contrast, cycle control with the biphasic pill was comparable to that with the triphasic pill containing the same progestin (norethindrone). The available evidence is limited and of poor quality; the internal validity of these trials is questionable. Given the high losses to follow-up after randomization, these reports may be better considered observational in nature. Given that caveat, the biphasic pill containing norethindrone was associated with inferior cycle control compared with the triphasic pill containing levonorgestrel. This suggests that the choice of progestin may be more important that the phasic regimen in determining bleeding patterns.

Intrauterine growth retardation predisposes to insulin resistance but not to hyperandrogenism in young women.

It was recently suggested that precocious pubarche associated with subsequent functional ovarian hyperandrogenism and hyperinsulinemia could have a common origin in reduced fetal growth. We previously reported that young women born with intrauterine growth retardation (IUGR: birth weight less than the third percentile) were hyperinsulinemic and less insulin sensitive than women born with normal birth weight. The aim of the present study was to investigate whether these IUGR-born women demonstrated hyperandrogenism compared with controls. Our study population was composed of 130 IUGR-born women and 150 controls, of similar age (20.6 +/- 3.2 vs. 20.4 +/- 2.0 yr). Hormonal contraception in terms of frequency and medication, including antiandrogenic therapy, was identical in the 2 groups. After adjustment for hormonal contraception, being born with IUGR had no independent effect on serum androgen concentrations. In women who were not receiving hormonal contraception, no statistical differences were found between IUGR-born women (n = 67) and controls (n = 64) for delta4-androstenedione (2.26 +/- 0.68 vs. 2.24 +/- 0.55 ng/mL; P = 0.76), dehydroepiandrosterone sulfate (2294 +/- 1117 vs. 2489 +/- 1235 ng/mL; P = 0.24), testosterone (0.82 +/- 0.85 vs. 0.70 +/- 0.26 ng/mL; P = 0.80), or serum sex hormone-binding protein concentrations (45.5 +/- 28.2 vs. 53.1 +/- 30.3 nmol/L; P = 0.27). In both IUGR and control groups, sex hormone-binding protein correlated negatively with fasting insulin (r = -0.23; P = 0.03 and r = -0.26; P = 0.05), but serum androgen levels did not correlate with insulin. In summary, hyperinsulinemia observed in young women born with IUGR is not associated with hyperandrogenism. Consequently, our results do not support the hypothesis of a common in utero programming of hyperandrogenism and hyperinsulinemia.

Levonorgestrel subdermal implants. A review of contraceptive efficacy and acceptability.

Levonorgestrel 6-capsule subdermal implants (Norplant) are an effective form of reversible contraception. When implanted under the skin of the upper arm, they release drug into the circulation at a relatively constant rate over 5 years. Generally, the cumulative pregnancy rate at the end of 5 years' levonorgestrel implant use is less than 2 per 100 users. The implants provide contraceptive efficacy equivalent to, or better than, that provided by other reversible methods (including oral contraceptives). Younger women are more likely than older women to become pregnant while using levonorgestrel implants. Bodyweight was positively correlated with risk of pregnancy in a number of studies, but may not be a factor with the currently available 6-capsule implant formulation. Limited data suggest that a new 2-rod levonorgestrel subdermal system (Jadelle) is as effective as the more extensively studied 6-capsule system and has a similar tolerability profile. Fertility returns rapidly after the implants are removed. Use of levonorgestrel subdermal implants is compatible with breast-feeding. In several studies, discontinuation rates were 2 to 15% during the first year of use; cumulative 5-year discontinuation rates ranged from 22 to 64 per 100 women. Despite a substantial incidence of adverse events during therapy, levels of user satisfaction are generally high. Menstrual abnormalities (increased or decreased menstrual flow, spotting, irregularity and amenorrhoea) affect most women at some time during therapy and are the most frequent reason for discontinuing levonorgestrel implants before the end of 5 years' treatment (incidence of 4.2 to 30.7 per 100 users). Mood changes and headache also may lead to discontinuation. Other reported adverse events include skin reactions (including acne), dizziness and weight gain. Serious adverse events (such as stroke, thrombotic thrombocytopenia and idiopathic intracranial hypertension) have been reported during levonorgestrel implants therapy, but the population incidence is difficult to calculate and causality is unclear. According to 3 pharmacoeconomic analyses from an institutional or managedcare perspective, all contraceptive interventions result in net cost savings. It is not clear whether levonorgestrel implants provide greater or smaller economic benefits than combined oral contraceptives. Levonorgestrel subdermal implants provide effective long term contraception. Despite a high incidence of menstrual adverse events, overall levels of user satisfaction are high, and 1-year continuation rates are better than those for combined oral contraceptives. Levonorgestrel subdermal implants are a good choice of contraceptive method in women who desire effective contraception, but who are unable to, or prefer not to, comply with an oral regimen.

Breast cancer and hormonal contraceptives: further results: Collaborative group on hormonal factors in breast cancer

The Collaborative Group on Hormonal Factors in Breast Cancer has brought together and reanalysed the worldwide epidemiological evidence on breast cancer risk and use of hormonal contraceptives. Original data from 54 studies, representing about 90% of the information available on the topic, were collected, checked and analysed centrally. The 54 studies were performed in 26 countries and include a total of 53,297 women with breast cancer and 100,239 women without breast cancer. The studies were varied in their design, setting and timing. Most information came from case-control studies with controls chosen from the general population; most women resided in Europe or North America and most cancers were diagnosed during the 1980s. Overall 41% of the women with breast cancer and 40% of the women without breast cancer had used oral contraceptives at some time; the median age at first use was 26 years, the median duration of use was 3 years, the median year of first use was 1968, the median time since first use was 16 years, and the median time since last use was 9 years. The main findings, summarised elsewhere, are that there is a small increase in the risk of having breast cancer diagnosed in current users of combined oral contraceptives and in women who had stopped use in the past 10 years but that there is no evidence of an increase in the risk more than 10 years after stopping use. In addition, the cancers diagnosed in women who had used oral contraceptives tended to be less advanced clinically than the cancers diagnosed in women who had not used them. Despite the large number of possibilities investigated, few factors appeared to modify the main findings either in recent or in past users. For recent users who began use before age 20 the relative risks are higher than for recent users who began at older ages. For women whose use of oral contraceptives ceased more than 10 years before there was some suggestion of a reduction in breast cancer risk in certain subgroups, with a deficit of tumors that had spread beyond the breast, especially among women who had used preparations containing the highest doses of oestrogen and progestogen. These findings are unexpected and need to be confirmed. Although these data represent most of the epidemiological evidence on the topic to date, there is still insufficient information to comment reliably about the effects of specific types of oestrogen or of progestogen. What evidence there is suggests, however, no major differences in the effects for specific types of oestrogen or of progestogen and that the pattern of risk associated with use of hormonal contraceptives containing progestogens alone may be similar to that observed for preparations containing both oestrogens and progestogens. On the basis of these results, there is little difference between women who have and have not used combined oral contraceptives in terms of the estimated cumulative number of breast cancers diagnosed during the period from starting use up to 20 years after stopping. The cancers diagnosed in women who have used oral contraceptives are, however, less advanced clinically than the cancers diagnosed in never users. Further research is needed to establish whether the associations described here are due to earlier diagnosis of breast cancer in women who have used oral contraceptives, to the biological effects of the hormonal contraceptives or to a combination of both. Little information is as yet available about the effects on breast cancer risk of oral contraceptive use that ceased more than 20 years before and as such data accumulate it will be necessary to re-examine the worldwide evidence.

An alternative thought-experiment

I believe the proposed solution is nothing but a sure way of promoting adolescent promiscuity and advocating eventual adult irresponsibility not only in matters of sexuality but also in those of family life. I have worked with adolescent girls over a period of 16 years. I cannot imagine subjecting a 12 year old to long term contraception for five years. During those very formative years is she to be deprived of the opportunity to develop a sense of self-control and sexual discipline and then expected to practise these values later in life? I also abhor the comparison of long-term contraception to immunisation. Immunisation is necessary for disease prevention and control. Sexual involvement on the other hand is a deliberate action of choice. The editorial seems to be playing down the moral value of other contraceptive devices that require user co-operation. Is it advocating robotism in the sexual domain? (excerpt)

Vaccine contraceptives: Wisdom, optimism and combatting the potential for abuse

Vaccine contraceptives are still in the early stages of development and in two cases clinical trials. In RHM 3 we published a paper by P David Griffin et al which described how these contraceptives would work if they proved to be safe and effective enough for use. For RHM 4, we invited a number of people to respond to that paper, to take up some of the controversial issues the research has generated. For the past year a petition calling for a stop to this research has been circulated by the coordination office of the Women's Global Network for Reproductive Rights (WGNRR) and others on the grounds that these contraceptives would: 1) have a higher abuse potential than any existing method; 2) have many potential health risks; 3) present no advantages for women over existing contraceptives in terms of efficacy, safety, protection against sexually transmitted diseases or control by the user; and 4) arise from a demographically driven, science-led framework that distorts contraceptive research priorities. The papers that follow reflect on and respond to the views in that petition as well as to those of Griffin et al.

Tubal sterilization and subsequent ectopic pregnancy. A case-control study

<h3>Objective.</h3> —To assess the relative risk of ectopic pregnancy associated with postpartum or interval tubal sterilization. <h3>Design.</h3> —Case-control study using a comparison group of women of reproductive age at risk of pregnancy. <h3>Setting.</h3> —Group Health Cooperative of Puget Sound, a health maintenance organization based in Seattle, Wash. <h3>Participants.</h3> —Cases were 249 enrollees diagnosed as having an ectopic pregnancy between October 1, 1981, and September 30, 1986. Controls were 835 randomly selected enrollees matched to cases on age and county of residence. <h3>Measurements.</h3> —Information on interval sterilization history was obtained from interviews, examination of medical records, automated hospitalization files, and a previously validated algorithm. A logistic regression model was used to estimate relative risks (RRs) for sterilized women compared with women using other types of or no contraception at the reference date. <h3>Results.</h3> —Controlling for age, county, race, smoking, income, gravidity, and prior use of a Dalkon Shield intrauterine device, the risk of ectopic pregnancy in women who had undergone interval sterilization was 3.7 (95% confidence interval [Cl], 1.7 to 8.0) times that of women currently using oral contraception and 2.8 (95% Cl, 1.5 to 5.5) times that of women currently using barrier contraceptive methods. Use of interval sterilization was associated with a risk of ectopic pregnancy similar to that of women using intrauterine devices (RR, 0.8; 95% Cl, 0.4 to 1.7) and a risk lower than that of women who were not using contraception (RR, 0.2; 95% Cl, 0.1 to 0.3). The corresponding RRs associated with postpartum sterilization were lower: 1.2 (95% Cl, 0.3 to 3.9), 0.9 (95% Cl, 0.3 to 2.8), 0.3 (95% Cl, 0.1 to 0.8), and 0.1 (95% Cl, 0.0 to 0.2), respectively. <h3>Conclusion.</h3> —Tubal sterilization provides some protection against extrauterine as well as intrauterine pregnancy. It is likely that postpartum sterilization can be a safe alternative to all types of temporary contraception in terms of risk of ectopic pregnancy, while some types of interval sterilization may lead to an increased risk, in comparison with use of oral contraceptives or barrier methods. (<i>JAMA</i>. 1991;266:242-246)

Tubal Sterilization and Subsequent Ectopic Pregnancy

To assess the relative risk of ectopic pregnancy associated with postpartum or interval tubal sterilization. Case-control study using a comparison group of women of reproductive age at risk of pregnancy. Group Health Cooperative of Puget Sound, a health maintenance organization based in Seattle, Wash. organization based in Seattle, Wash. Cases were 249 enrollees diagnosed as having an ectopic pregnancy between October 1, 1981, and September 30, 1986. Controls were 835 randomly selected enrollees matched to cases on age and county of residence. Information on interval sterilization history was obtained from interviews, examination of medical records, automated hospitalization files and a previously validated algorithm. A logistic regression model was used to estimate relative risks (RRs) for sterilized women compared with women using other types of or no contraception at the reference date. Controlling for age, county, race, smoking, income, gravidity, and prior use of a Dalkon Shield intrauterine device, the risk of ectopic pregnancy in women who had undergone interval sterilization was 3.7 (95% confidence interval [CI], 1.7 to 8.0) times that of women currently using oral contraception and 2.8 (95% CI, 1.5 to 5.5) times that of women currently using barrier contraceptive methods. Use of interval sterilization was associated with a risk of ectopic pregnancy similar to that of women using intrauterine devices (RR, 0.8; 95% CI, 0.4 to 1.7) and a risk lower than that of women who were not using contraception (RR, 0.2; 95% CI, 0.1 to 0.3). The corresponding RRs associated with postpartum sterilization were lower: 1.2 (95% CI, 0.3 to 3.9), 0.9 (95% CI, 0.3 to 2.8), 0.3 (95% CI, 0.1 to 0.8), and 0.1 (95% CI, 0.0 to 0.2), respectively. Tubal sterilization provides some protection against extrauterine as well as intrauterine pregnancy. It is likely that postpartum sterilization can be a safe alternative to all types of temporary contraception in terms of risk of ectopic pregnancy, while some types of interval sterilization may lead to an increased risk, in comparison with use of oral contraceptives or barrier methods.

Awareness of the existence of postcoital contraception among students who have had a therapeutic abortion.

Abstract A two-semester survey was conducted to obtain information about the underutilization of postcoital contraception (PCC) in terms of fear about using it or ignorance of its existence. Among 437 students attending the women's health clinic at California State University/Fresno, 41% had had a therapeutic abortion. One hundred fifty-two, or 84.9%, of those who had had terminations were not aware of PCC. Some were not aware that they had taken a chance of becoming pregnant. It is concluded that students who have had a therapeutic abortion either were unaware of the existence of PCC or were unaware they were risking pregnancy and therefore unable to utilize PCC to avoid the need for a surgical procedure. It would appear that ignorance about the existence of PCC is a major reason for its underutilization. “Treatment of First Episodes of Genital Herpes Simples Virus Infection with Oral Acyclovir,” YVONNE J. BRYSON, MARYANNE DILLON, MICHAEL LOVETT, GUILLERMO ACUNA, STEPHEN TAYLOR, JAMES D. CHERRY, B. LAMAR...

Postcoital IUD insertion, a review

Following the development of hormonal interception after coitus the post-coital insertion of an intrauterine contraceptive device was proposed by Tatum . The advantage of this treatment is the avoidance of the ingestion of large doses of estrogen which causes much nausea and vomiting although it is a very effective post-coital method of contraception. The recently proposed alternative administration of 200 micrograms Ethynol Estradiol combined with 2 mg of DL norgesterol in 2 equal doses at 12 hour intervals has the same disadvantage of a high percentage of side effects. The post-coital insertion of an intrauterine contraceptive device is the first method which is effective up to five days following unprotected intercourse which is three days longer than treatment by estrogen. In addition the method can be offered to women who would want to continue to wear the intrauterine contraceptive device for long term contraception. The disadvantage of the post-coital insertion of an intrauterine contraceptive device is the ability of serious complications if the patient has a vaginal or venereal infection or an asymptomatic cervicitis or salpingitis. Following appropriate physical examination women who present themselves for post-coital treatment are selected. Cases of rape are usually not suitable for treatment with intrauterine contraceptives devices. However, when cases of rape are seen early enough the appropriate investigations may be done and the treatment with the intrauterine device started within five days. The potential risk of future infertility must be considered since salpingitis is 7 times more common in nulliparous wearers of intrauterine devices than in nulliparous non-wearers. Young sexually active nulliparous women especially of lower socio economic background are patients with a high risk. Over 70% of the women who present themselves for interception treatment are nulliparous.(ABSTRACT TRUNCATED AT 250 WORDS)

Multinational comparative clinical trial of long-acting injectable contraceptives: Norethisterone enanthate given in two dosage regimens and depot-medroxyprogesterone acetate. Final report: Who special programme of research, development and research training in human reproduction

Final results are presented from a two-year WHO multinational comparative trial of three regimens: depot-medroxyprogesterone acetate (DMPA) given at 90-day intervals, norethisterone enantate (NET-EN) given at 60-day intervals for the entire study period (NET-EN (60-day)), and NET-EN given at 60-day intervals for six months and thereafter at 84-day intervals (NET-EN (84-day)). 1587 DMPA subjects were observed for 20,550 woman-months, 789 NET-EN (60-day) subjects were observed for 10,361 woman-months, and 796 NET-EN (84-day) subjects were observed for 10,331 woman-months. This clinical trial represents the largest clinical trial undertaken on injectable contraceptives. After two years, the pregnancy rate with NET-EN (84-day) was 1.4 (±0.6 S.E.) per 100 women, as compared with the two-year rates of 0.4 (±0.3 S.E.) per 100 women observed with DMPA and 0.4 (± 0.2 S.E.) with NET-EN (60-day). Both discontinuation rates for amenorrhea and the prevalence of amenorrhea lasting more than 90 days were significantly higher with DMPA than with either NET-EN regimen. Terminations for bleeding problems were similar with the three treatments, despite a better cyclic pattern for the first six months with the NET-EN regimens. The three treatments were comparable with respect to discontinuation rates for other medical or personal reasons, and for all reasons combined. For family planning programs, NET-EN (60-day) has the advantage of low pregnancy rates compared to NET-EN (84-day), and a schedule of administration that does not change. Both NET-EN regimens produce less amenorrhea than DMPA. However, the NET-EN (60-day) regimen has the logistic and economic disadvantage of requiring more frequent injections. All three injectable regimens compare favourably with oral contraceptives in terms of pregnancy and total continuation rates observed in clinical trial settings.

Influence of the LH-RH analogue buserelin on cyclic ovarian function and on endometrium. A new approach to fertility control?

The long-acting stimulatory luteinizing hormone — releasing hormone analogue D-Ser(TBU) 6-EA 10-LH-RH (buserelin) was administered intranasally once daily in a dose of 400 mcg to 24 normally ovulating women and to 4 women with pre-existing endocrine dysregulation. Ovulation was inhibited in 136 out of 156 treatment months. In 20 treatment months, progesterone values temporarily increased indicating luteinization of follicles or ovulation with defective corpus luteum function. Estradiol secretion showed a tendency to lower values as treatment progressed but individually indicated follicle maturation until the end of the observed medication period. Bleeding pattern ranged from menses-like bleeding in regular as well as irregular intervals to amenorrhea. The morphological findings of 31 endometrial biopsies of 20 volunteers ranged from atrophy ( n = 4) to proliferation ( n = 25) with early signs of hyperplasia as well as early secretory transformation ( n = 2). The morphological alterations indicate that unopposed estrogen stimulation of the endometrium is the main problem of long — term contraception with the dose schedule of buserelin used.

Contraceptive behavior in adolescence: a decision-making perspective.

The contraceptive behavior of adolescent girls was viewed from a decision-making perspective. A semistructured interview protocol was used in interviewing 120 girls aged 12–19 in three clinics (Teen Family Planning, Prenatal, Pediatric Acute Care) at Michael Reese Hospital and Medical Center on (1) demographic in formation; (2) sexual and obstetric history; (3) contraceptive and sexual knowledge, attitudes, and practices; (4) environmental pressures; (5) personality factors; and (6) decision-making style. We found that the girls were generally poor contraceptors. They viewed the costs of contraception (in terms of safety) to be high; and they positively valued physical intimacy, opportunities for which come up unexpectedly and sporadically. These factors, along with their ambivalent views toward pregnancy and childbearing seemed to encourage their risk-taking behavior. Once pregnancy occurred, it was carried to term because of the strong internal and external pressures they felt to have and keep the baby. The peer-led intervention program that we are developing based on the survey findings will focus on (1) the teenagers' lack of accurate and complete knowledge about birth control and conception, (2) their limited sense of options concerning birth control and pregnancy outcomes, and (3) their poor understanding of and lack of insight into what motivates their behavior.

Oral Contraceptive Potencies and Side Effects

A set of empirical results is used to test a model that assigns rankings to oral contraceptives in terms of relative hormonal potencies. The association between the observed incidence of side effects attributed to excess of estrogen and progestin and their incidence as predicted by the model is analyzed. Results of the study show the model to have incorrectly predicted the observed ranking order of symptoms associated with excess estrogen. Further, while the model correctly predicted the oral contraceptive with the highest progestogenic potency (Ovral), the observed ranking order of the other two preparations is shown to be the reverse of that predicted by the model.

Oral Progestins in Fertility Control: A Comparative Study

Results are presented from centers in Mexico City San Antonio Texas and Columbus Ohio where 6 different progestational agents were used for fertility control. The subjects were multiparous women requesting the oral tablet to space their pregnancies. The series included 2040 women who accumulated a total of 22948 treatment cycles. The compounds were 100% effective in fertility control when taken as prescribed. In Mexico 61% of the women became pregnant in the first month after discontinuing norethindrone 10 mg. 92% were pregnant by the end of 3 months posttreatment. The observation was made that the effectiveness of norethindrone 10 mg may not be due to ovulation inhibition alone but to a combination of factors. Breakthrough bleeding and undesirable side reactions with the various compounds were minimal and transitory. The lowest incidence of side effects was with norethindrone 10 mg. The incidence of chloasma appeared to be related to malnutrition. There were no malignant nor premalignant changes in the cervix nor in the endometrium following treatment. Lactation was diminished or stopped in approximately 1 out of 3 cases on norethindrone 10 mg. The changes in the endometrium which were brought about by the medication were shown to be completely reversible when treatment was stopped. Libido tended to normalize. In the populations studied oral contraception in terms of effectiveness and acceptability appears to be far superior to any other available method.

BIRTH CONTROL AND CONTRACEPTION

To the Editor:— editorial on Birth Control and Contraception inThe Journal, September 8, is naturally of interest to the National Committee on Maternal Health, which since 1923 has been studying these and allied questions as problems of public health and the practice of medicine. Since 1929 we have conducted a systematic and comprehensive investigation into the nature and merits of various contraceptive products and methods. result of the first three years study, done in cooperation with the University of Edinburgh, was published in a volume by Cecil I. B. Voge, Ph.D., F.R.S.E., F.R.S.M., under the title of The Chemistry and Physics of Contraceptives (London, Jonathan Cape, 1933). Voge's study established the factual basis for the evaluation of contraceptives in terms of physics, chemistry and biology. next step was obviously to apply the tests to the commercial products now most widely used and exploited, and concomitantly the