25 years, 25 articles: Studies you should know

Click here to see 25 important events in reproductive health.

Research has been a cornerstone of contraceptive technology; the following noninclusive list includes 25 articles of note from the past 25 years.

Several selections are offered by Deborah Kowal, MA, adjunct assistant professor in the Rollins School of Public Health at Emory University in Atlanta, co-author of Contraceptive Technology, and the first editor for Contraceptive Technology Update. Kowal’s presentation on top medical literature is a perennial favorite at the Contraceptive Technology conferences. The 2005 conferences are scheduled for March 9-12, 2005, in San Francisco and April 6-9, 2005, in Washington, DC. [More information is available at www.contemporaryforums.com or by calling (800) 377-7707, or e-mailing info@cforums.com.]

Click here to see what the experts have to say about advances in reproductive health.


1. Beral V, Bull D, Doll R, et al. Breast cancer and abortion: Collaborative reanalysis of data from 53 epidemiological studies, including 83,000 women with breast cancer from 16 countries. Lancet 2004; 363:1,007-1,016.

Data on women from 53 studies undertaken in 16 countries with liberal abortion laws were analyzed, with researchers concluding that pregnancies that end as a spontaneous or induced abortion do not increase a woman’s risk of developing breast cancer.


2. Audet MC, Moreau M, Koltun WD, et al. Evaluation of contraceptive efficacy and cycle control of a transdermal contraceptive patch vs. an oral contraceptive: A randomized controlled trial. JAMA 2001; 285:2,347-2,354.

Researchers designed an open-label, parallel-group trial, randomly assigning women to use of the transdermal contraceptive or an oral contraceptive (OC).

Findings indicate that the contraceptive patch is comparable to a combination OC in contraceptive efficacy and cycle control. Compliance was better with the weekly contraceptive patch than with the OC.

3. Roumen FJ, Apter D, Mulders TM, et al. Efficacy, tolerability, and acceptability of a novel contraceptive vaginal ring releasing etonogestrel and ethinyl oestradiol. Hum Reprod 2001; 16:469-475.

This yearlong, multicenter study assessed the contraceptive efficacy, cycle control, tolerability, and acceptability of the contraceptive vaginal ring. Findings indicate that the method is effective and well accepted.

Depot medroxyprogesterone acetate (DMPA)

4. Strom BL, Berlin JA, Weber AL, et al. Absence of an effect of injectable and implantable progestin-only contraceptives on subsequent risk of breast cancer. Contraception 2004; 69:353-360.

This study analyzed the relationship between breast cancer and use of injectable and implantable progestin-only contraceptives. Results indicate that progestin-only implants and injectables do not raise a woman’s risk of breast cancer.

Emergency contraception

5. Von Hertzen H, Piaggio G, Ding J, et al. Low-dose mifepristone and two regimens of levonorgestrel for emergency contraception: a WHO multicentre randomised trial. Lancet 2002; 360:1,803-1,810.

A randomized, double-blind trial in 10 countries showed that the three regimens studied are effective and prevent a high proportion of pregnancies if taken within five days of unprotected coitus. A 1.5 mg single levonorgestrel dose can substitute for two 0.75 mg doses 12 hours apart.

Family planning

6. Arevalo M, Sinai I, Jennings V. A fixed formula to define the fertile window of the menstrual cycle as the basis of a simple method of natural family planning. Contraception 2000; 60:357-360.

This article reports the results of an analysis of the application of a fixed formula to define the fertile window. By analyzing a large data set, researchers determined a fixed formula in which days 8-19 of the menstrual cycle are considered to be the fertile window. This research is the basis for the Standard Days Method.

7. Stewart FH, Harper CC, Ellertson CE, et al. Clinical breast and pelvic examination requirements for hormonal contraception: Current practice vs. evidence. JAMA 2001; 285:2,232-2,239.

After performing a review of current literature, the authors conclude that hormonal contraception can safely be provided based on careful review of medical history and blood pressure measurement. For most women, no further evaluation is necessary.

8. Trussell J, Hatcher RA, Cates Jr. W, et al. Contraceptive failure in the United States: An update. Stud Fam Plann 1990; 21:51-54.

This report updates the authors’ previous estimates of first-year probabilities of contraceptive failure for all methods of contraception. Estimates are provided of failure during typical use (which includes incorrect and inconsistent use) and during perfect use (correct use at every act of intercourse). The difference between these two probabilities provides a measure of how forgiving of imperfect use each method is.

9. Wilcox AJ, Weinberg CR, Baird DD. Timing of sexual intercourse in relation to ovulation. Effects on the probability of conception, survival of the pregnancy, and sex of the baby. N Engl J Med 1995; 333:1,517-1,521.

A total of 221 healthy women, who were planning to become pregnant, stopped using birth-control methods and began collecting daily urine specimens and keeping daily records of whether they had sexual intercourse. Findings indicated that among healthy women trying to conceive, nearly all pregnancies can be attributed to intercourse during a six-day period ending on the day of ovulation.

10. World Health Organization (WHO). Medical Eligibility Criteria for Contraceptive Use. 3rd ed. Geneva; 2003.

The latest update of the WHO Medical Eligibility Criteria provides current guidance on provision of contraceptives.


11. Centers for Disease Control and Prevention. Pneumocystis pneumonia — Los Angeles. MMWR 1981; 30:250-252.

12. Centers for Disease Control and Prevention. Kaposi’s sarcoma and Pneumocystis pneumonia among homosexual men — New York City and California. MMWR 1981; 30:305-308.

In 1981, clinical investigators in New York and California observed the first evidences of HIV/ AIDS infection in the United States: An unusual clustering of cases of rare diseases, notably Kaposi’s sarcoma, and opportunistic infections such as Pneumocystis carinii pneumonia among young, previously healthy, homosexual men.

13. Connor EM, Sperling RS, Gelber R, et al. Reduction of maternal-infant transmission of human immunodeficiency virus Type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N Engl J Med 1994; 331: 1,173-1,180.

Scientists conducted a randomized, double-blind, placebo-controlled trial of the efficacy and safety of zidovudine in reducing the risk of maternal-infant HIV transmission.

In pregnant women with mildly symptomatic HIV disease and no prior treatment with antiretroviral drugs during the pregnancy, a regimen consisting of zidovudine given ante partum and intrapartum to the mother and to the newborn for six weeks reduced the risk of maternal-infant HIV transmission by approximately two-thirds.

Hormone therapy

14. Chlebowski RT, Hendrix SL, Langer RD, et al. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: The Women’s Health Initiative Randomized Trial. JAMA 2003; 289:3,243-3,253.

The Women’s Health Initiative trial of combined estrogen plus progestin was stopped early when overall health risks, including invasive breast cancer, exceeded benefits. Results from this analysis suggest estrogen plus progestin may stimulate breast cancer growth and hinder breast cancer diagnosis.

15. Grady D, Herrington D, Bittner V, et al. Cardiovascular disease outcomes during 6.8 years of hormone therapy. JAMA 2002; 288:49-57.

Investigators analyzed results from the Heart and Estrogen/progestin Replacement Study (HERS), a randomized, blinded, placebo-controlled trial of 4.1 years’ duration (HERS) and subsequent unblinded follow-up for 2.7 years. Researchers conclude that postmenopausal hormone therapy should not be used to reduce risk for coronary heart disease (CHD) events in women with CHD.

16. Hulley S, Furberg C, Barrett-Connor E, et al. Noncardiovascular disease outcomes during 6.8 years of hormone therapy. JAMA 2002; 288:58-66.

Further analysis of the HERS study data showed that treatment for 6.8 years with estrogen plus progestin in older women with coronary disease increased the rates of venous thromboembolism and biliary tract surgery.

Intrauterine devices (IUDs)

17. Alvarez F, Brache V, Fernandez E, et al. New insights on the mode of action of intrauterine contraceptive devices in women. Fertil Steril 1988; 49:768-773.

To gain a better understanding of the mechanism of action of intrauterine devices, a search was made for ova in the genital tracts of 115 women using no contraception and of 56 women using IUDs, all of whom volunteered for study in conjunction with surgical sterilization.

Fertilized ova are less likely to reach the uterine cavity containing an IUD, researchers observed, thus leading them to conclude that the principal mode of IUDs is by a method other than destruction of live embryos.

18. Grigorieva V, Chen-Mok M, Tarasova M, et al. Use of a levonorgestrel-releasing intrauterine system to treat bleeding related to uterine leiomyomas. Fertil Steril 2003; 79:1,194-1,198.

Designed as a prospective before-and-after study of women with uterine leiomyomas who chose the levonorgestrel intrauterine system as their method of contraception, researchers found that the device was associated with a profound reduction in menstrual blood loss and may provide effective medical treatment of bleeding.

19. Hubacher D, Lara-Ricalde R, Taylor DJ, et al. Use of copper intrauterine devices and the risk of tubal infertility among nulligravid women. N Engl J Med 2001; 345:561-567.

This case-control study helps refute the myths that IUDs cause pelvic infection, increase ectopic pregnancy, and are inappropriate for young or never-pregnant women.

20. Lee NC, Rubin GL, Borucki R. The intrauterine device and pelvic inflammatory disease revisited: New results from the Women’s Health Study. Obstet Gynecol 1988; 72:1-6.

Researchers analyzed data from the Women’s Health Study, a hospital-based, case-control study carried out in the United States from 1976-1978, to examine whether the risk of pelvic inflammatory disease associated with IUD use varies with a woman’s sexual behavior. Results indicated that women at low risk of acquiring sexually transmitted infections have little increase in the risk of pelvic inflammatory disease from use of an IUD.


21. Marchbanks PA, McDonald JA, Wilson HG, et al. Oral contraceptives and the risk of breast cancer. N Engl J Med 2002; 346:2,025-2,032.

Findings from this population-based, case-control study indicate that among women from 35 to 64 years of age, current or former OC use was not associated with a significantly increased risk of breast cancer.

22. Oral contraceptive use and the risk of ovarian cancer. The Centers for Disease Control Cancer and Steroid Hormone Study. JAMA 1983; 249:1,596-1,599.

The Centers for Disease Control and Prevention in Atlanta published this report as part of its Cancer and Steroid Hormone Study, a multicenter, case-control investigation. Researchers determined that the risk of ovarian cancer decreased with increasing duration of OC use and remained low long after cessation of use and estimated that more than 1,700 cases of ovarian cancer are averted each year by past and current OC use among American women.

23. The reduction in risk of ovarian cancer associated with oral-contraceptive use. The Cancer and Steroid Hormone Study of the Centers for Disease Control and the National Institute of Child Health and Human Development. N Engl J Med 1987; 316:650-655.

Researchers used data from a case-control study, the Cancer and Steroid Hormone Study, to evaluate the reduction in risk of ovarian cancer associated with OC use. A protective effect was seen in women who had used OCs for as little as three to six months, and it continued for 15 years after use ended. It was independent of the specific OC formulation and of the histologic type of epithelial ovarian cancer. Findings indicate that the OC use decreases the risk of epithelial ovarian cancer.

24. Westhoff C, Kerns J, Morroni C, et al. Quick Start. A novel oral contraceptive initiation method. Contraception 2002; 66:141-145.

Investigators at an urban family planning clinic routinely offer patients starting contraceptive pills the option of taking the first tablet sooner. A telephone follow-up showed that women who swallowed the first OC in the clinic were more likely to continue the OC until the second package than women who planned to start the pills later.


25. Peterson HB, Xia Z, Hughes JM, et al. The risk of pregnancy after tubal sterilization: Findings from the U.S. Collaborative Review of Sterilization. Am J Obstet Gynecol 1996; 174:1,161-1,168; discussion 1,168-1,170.

A multicenter, prospective cohort study was conducted in U.S. medical centers, with more than 10,000 women who underwent tubal sterilization followed for eight to 14 years.

The risk of pregnancy was assessed by cumulative life-table probabilities and proportional hazards models. Findings indicate although tubal sterilization is highly effective, the risk of sterilization failure is higher than generally reported. The risk persists for years after the procedure and varies by method of tubal occlusion and age.