Look to the future for bold changes in reproductive health

Microbicides and male contraceptives soon may be added to the list

(Editor’s note: This issue of Contraceptive Technology Update marks the 25th anniversary of the newsletter. In this issue, you’ll see observations from reproductive health experts, reviews of important research, and a timeline of reproductive health events. We hope you enjoy this special edition of CTU.)

Look ahead five to 10 years, and you may see a male contraceptive on the market, as well as a microbicide for women that offers contraception as well as female-controlled protection against HIV and other sexually transmitted diseases (STDs), say reproductive health experts.

Researchers are examining different approaches to identifying molecules controlling spermatogenesis and oocyte maturation, sperm-egg fusion, and endometrial implantation of the early embryo. By applying genomics and proteomics technology or building upon genetic analysis of model organisms, scientists hope to unlock new discoveries that will lead to more contraceptive options.1

"The future will be very much influenced by new pharmaceutical agents," forecasts Leon Speroff, MD, associate director of the Women’s Health Research Unit at Oregon Health & Science University in Portland. "The knowledge gained from molecular biology allows the development of drugs that will target specific tissues and functions, minimizing unwanted effects."

New methods of contraception must be made available if the challenge of unmet need is to be effectively addressed. According to a recent Washington, DC-based Institute of Medicine publication, more than a quarter of pregnancies worldwide are unintended. Between 1995 and 2000, nearly 700,000 women died and many more experienced illness, injury, and disability as a result of unintended pregnancy.2

"Our biggest current problem is maternal morbidity and mortality around the world due to a lack of acceptance of post-ovulatory methods of contraception," states David Archer, MD, professor of obstetrics and gynecology and director of the Clinical Research Center at the Eastern Virginia Medical Center in Norfolk. "We need to address this issue directly; reducing maternal mortality should be our key message."

Zeroing in on men

One of the greatest family planning achievements in the past 25 years has been the acceptance by the majority of U.S. women of the use of oral steroidal contraception, reports Archer. Women’s acceptance of hormonal contraception is a tacit understanding of the need to limit family size and most importantly, the safety of the method, he notes.

But when it comes to contraception for men, similar progress has not yet been achieved. According to results of a 2000 survey, men are interested, with most favoring a pill, but many signaling acceptance of an implant or injection.3

Progress may be forthcoming, says Régine Sitruk-Ware, MD, executive director for product research and development at the Center for Biomedical Research at the New York City-based Population Council, a nonprofit research organization. The Population Council is actively researching male contraceptive methods, says Sitruk-Ware, who participated in "Reproductive Health in the Twenty-First Century," an October 2004 conference sponsored by the Cambridge, MA-based Harvard University’s Radcliffe Institute for Advanced Study. The Population Council is researching use of its trademarked synthetic androgen, 7-alpha-methyl-19-nortestosterone (MENT) as a possible male contraceptive. Scientists are studying use of the androgen since it suppresses gonadotropin secretion, which leads to suppression of testosterone and sperm production in the testes.

Pharmaceutical companies Schering AG of Berlin and Organon International of Oss, The Netherlands, are jointly investigating a hormonal method of contraception for men. Scientists are looking at a gestagen implant and a testosterone injection in Phase II trials.

Just-published research indicates that male immunocontraception may be a viable option.4 Scientists injected Eppin, a testis/epididymis-specific protein, in male monkeys, making them infertile. When the injections were stopped, the monkeys regained their fertility status. Such early research may provide an avenue for larger scale examinations.

Focus on benefits

Expect to see more contraceptive methods with noncontraceptive benefits, says Sitruk-Ware. The levonorgestrel intrauterine system (Mirena IUS, Berlex Laboratories, Montville, NJ), which was developed by the Population Council, is being examined for potential use in treating menorrhagia.5

"The trend is that the contraceptive should bring added medical benefits in order to have more compliance with the system by the user, with more desire to use it and more support by the community," she states.

Pills will continue to represent an important contraceptive choice for women. New information presented at the 2004 annual meeting of the American Society for Reproductive Medicine highlighting the long-term noncontraceptive benefits of oral contraceptives (OCs) provides good news regarding OC safety, observes Andrew Kaunitz, MD, professor and assistant chair in the obstetrics and gynecology department at the University of Florida Health Science Center/Jacksonville.

The two presentations, based on Women’s Health Initiative (WHI) data, indicated that among postmenopausal women, risks of cardiovascular disease and certain cancers were lower among those WHI participants who had previously used oral contraception compared with those who had not, states Kaunitz.6,7

According to Kaunitz, upcoming oral contraceptive advances may include:

  • new options for women interested in extended oral contraception, including continuous OC formulations;
  • OC formulations with 24-25 active tablets per four-week cycle to enhance efficacy and cycle control;
  • pills formulated with progestins new to the United States that may enhance safety, efficacy, and tolerability;
  • OCs combined with folic acid to reduce the risk of birth defects when pregnancy occurs in the setting of current/recent OC use.

While significant progress has been made in the past 25 years when it comes to reproductive health, advocates will need to stay focused in helping to raise the status of women’s health worldwide. Unmet need for family planning remains high in developing countries, despite the recent accelerated growth in the use of contraception, according to the Geneva-based World Health Organization. For example, in sub-Saharan Africa, an average of 23% of women of reproductive age who are married or in union are believed to need family planning services.8

In the United States, women await an FDA decision on sale of over-the-counter emergency contraception. In addition, state and federal legislative changes may impact current women’s reproductive health choices. Two new editorials in family planning medical literature remind reproductive health clinicians of their need for advocacy for women’s rights.9,10

Felicia Stewart, MD, adjunct professor in the Department of Obstetrics, Gynecology, and Reproductive Sciences at the University of California San Francisco and co-director of its Center for Reproductive Health Research & Policy, and co-author of one of the editorials, says, "The last four years have been hard on reproductive health — for women in the U.S. and around the world; the next four years will be, too, so it is helpful to have a sense of priorities for our attention."

Advocates need to make sure that all efforts address the concerns of women in a comprehensive way, since a narrow focus cannot gain the broad support needed to empower women’s rights, she adds.

"Most of all, speaking up and not giving up are key; redoubled efforts are crucial if we hope to prevent further losses in funding and access to care," Stewart states.

References

1. Hollon T. Cutting-edge contraception. The Scientist Daily News Online. July 18, 2003; accessed at: www.biomedcentral.com/news/20030718/04.

2. Nass SJ, Strauss III JF, eds. New Frontiers in Contraceptive Research: A Blueprint for Action. Washington, DC: National Academies Press; 2004.

3. Martin CW, Anderson RA, Cheng L, et al. Potential impact of hormonal male contraception: Cross-cultural implications for development of novel preparations. Hum Reprod 2000; 15:637-645.

4. O’Rand MG, Widgren EE, Sivashanmugam RT, et al. Reversible immunocontraception in male monkeys immunized with eppin. Science 2004; 306:1,189-1,190.

5. Hurskainen R, Teperi J, Rissanen P, et al. Clinical outcomes and costs with the levonorgestrel-releasing intrauterine system or hysterectomy for treatment of menorrhagia: Randomized trial 5-year follow-up. JAMA 2004; 291:1,456-1,463.

6. Victory R, D’Souza C, Diamond MP, et al. Reduced cancer risks in oral contraceptive users: Results from the Women’s Health Initiative. Presented at the 60th annual meeting of the American Society for Reproductive Medicine. Philadelphia; October 2004.

7. Victory R, D’Souza C, Diamond MP, et al. Adverse cardiovascular disease outcomes are reduced in women with a history of oral contraceptive use: Results from the Women’s Health Initiative Database. Presented at the 60th annual meeting of the American Society for Reproductive Medicine. Philadelphia; October 2004.

8. World Health Organization. Majority of world’s couples of reproductive age are using contraception. Press release; April 21, 2004. Accessed at: www.un.org/esa/population/publications/contraceptive2003/WallChart_CP2003_pressrelease.htm.

9. Dickerson VM. The tolling of the bell: Women’s health, women’s rights. Obstet Gynecol 2004; 104:653-657.

10. Hwang HC, Shields WC, Stewart FH. Ten priorities for women’s health. Contraception 2004; 70:265-268.