2002 ANNUAL REPORT
Unraveling Mirena's molecular mystery

The contraceptive Mirena®, an intrauterine system, reduces excessive menstrual bleeding.

The contraceptive Mirena^® sharply reduces the excessive menstrual bleeding experienced by some women with uterine fibroids, the most common benign uterine tumors. Scientists are now beginning to understand the molecular mechanisms that account for this marked improvement in symptoms. 

Mirena, a progestin-releasing intrauterine system, was developed and tested collaboratively by the Population Council, its International Committee for Contraception Research, and the pharmaceutical company Leiras Oy (now known as Schering Oy). An extremely effective contraceptive, Mirena is now available in more than 100 countries and is being used by 5 million women.

“Mirena also offers a safe, nonsurgical alternative for the management of excessive menstrual bleeding that preserves the option of pregnancy,” says Elof D.B. Johansson. 

For example, Juan Díaz collaborated with colleagues at the Universidade Estadual de Campinas in Brazil to study the therapeutic use of Mirena in 44 women with heavy menstrual bleeding. The team found that after six months of use, “anemia was significantly reduced and surgical treatment was avoided in 80 percent of women studied," reports Diaz. 

Obstetrician and gynecologist Takeshi Maruo of Kobe University in Japan collaborated with Johansson, Council researcher Irving M. Spitz, and others to determine the underlying molecular cause of changes in the endometrium of women using Mirena. The investigators examined cellular changes in the endometrium, analyzing samples taken from 15 women before and three months after the insertion of Mirena. 

The researchers looked at four factors related to apoptosis, or genetically programmed cell death, in the endometrium. Apoptosis is a normal process in the menstrual cycle. PCNA, a marker of cell proliferation, was less abundant in the endometrium three months after the insertion of Mirena than it was before insertion. Bcl-2 protein, which is known to prevent apoptosis, was present in endometrial glands before the insertion of the device, but became scanty three months after insertion. Conversely, Fas antigen, which promotes apoptosis, was scarcely apparent before Mirena insertion, but predominant in the endometrium three months after insertion. Finally, the number of cells observed to be undergoing apoptosis in the endometrium was greater three months after the insertion of Mirena than it had been prior to insertion. 

"The increased apoptosis in the endometrium after insertion of Mirena may represent an underlying molecular mechanism that causes the endometrium to atrophy," says Maruo. "This in turn leads to improved management of heavy menstrual bleeding."

Juan Díaz is a senior program associate in the International Programs Division and country director in Brazil.	Elof D.B. Johansson is a Council vice president and director of the Center for Biomedical Research.	Takeshi Maruo is a member of the Council’s International Committee for Contraception Research.

See Also

• "Health benefits of Mirena," Momentum, May 2003