What causes POI?

What causes POI?

Restoring Bone Density in Women with Ovarian Disorder

10/02/2014 12:27 PM EDT

Source: National Institutes of Health - 
Related MedlinePlus Page: Ovarian Disorders

What Causes POI?

10/02/2014 12:27 PM EDT

Source: National Institute of Child Health and Human Development - 
Related MedlinePlus Page: Ovarian Disorders

Contact Us

E-mail: nihresearchmatters@od.nih.gov

Mailing Address:
NIH Research Matters
Bldg. 31, Rm. 5B64A, MSC 2094
Bethesda, MD 20892-2094

About NIH Research Matters

Editor: Harrison Wein, Ph.D.
Assistant Editors: Vicki Contie, Carol Torgan, Ph.D.

NIH Research Matters is a weekly update of NIH research highlights from the Office of Communications and Public Liaison, Office of the Director, National Institutes of Health.

Restoring Bone Density in Women with Ovarian Disorder

Share on emailShare on facebookShare on twitter

Hormone replacement therapy restored bone mineral density to normal in young women with primary ovarian insufficiency (POI). The findings provide important treatment information for women with POI and their physicians.

Spontaneous POI affects 1 in 100 women by age 40. With no apparent cause, the ovaries of affected women don’t work normally. They stop regularly releasing eggs and produce low levels of reproductive hormones, including estradiol (a type of estrogen) and testosterone (a predominantly male hormone that is also produced by women in smaller amounts). Women with POI have hot flashes, fertility problems, and irregular or no menstrual cycles. They also have reduced bone mineral density, which can lead to osteoporosis and bone fractures.

Hormone replacement therapy regimens have been well studied and optimized to improve bone health in postmenopausal women. But there has been limited research on the effects of these therapies in younger women. A team led by Drs. Vaishali B. Popat and Lawrence M. Nelson of NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) tested the effects of hormone replacement therapy on bone health in young women with POI. The trial was done at NIH’s Clinical Center in Bethesda, Maryland.

The team enrolled 145 women with POI between the ages of 18 and 42. The women were randomly assigned to 2 groups. One received an estradiol patch, progestin pills, and a testosterone patch. The other received an estradiol patch, progestin pills, and an inactive placebo patch. The researchers used bone density scans of the hip and lower spine to measure the effects of the regimens. For comparison, the scientists also measured bone mineral density in an untreated group of 70 women with normal ovarian function. Results were published online on June 6, 2014, in theJournal of Clinical Endocrinology & Metabolism.

Both hormone treatment regimens led to increases in bone mineral density at 3 years. When the study began, women with POI had significantly lower hip and spine bone mineral density levels than those in the control group. By the study’s end, bone density measures in both treatment groups had increased to the same level as the women without POI.

The group receiving a testosterone patch didn’t gain further benefits over those with a placebo patch. Studies with a greater number of women would be needed to learn whether testosterone replacement might benefit women with POI, the researchers note.

“While hormone replacement therapy’s effect on bone mineral density has been studied in postmenopausal women, there is limited research on the effects of this therapy in younger women,” Popat says.

“This study showed that not only could hormone treatment reduce the rate at which women with POI lose bone mineral density, but it could actually restore bone density to normal levels,” Nelson adds.

RELATED LINKS:

• Egg-Producing Stem Cells Found in Women:
  http://www.nih.gov/researchmatters/march2012/03052012egg.htm
• Too Young for Hot Flashes? When Menopause-Like Symptoms Come Too Soon:
  http://newsinhealth.nih.gov/issue/Jun2010/Feature2
• Primary Ovarian Insufficiency (POI):
  http://www.nichd.nih.gov/health/topics/poi/Pages/default.aspx
• Bone Basics:
  http://www.niams.nih.gov/Health_Info/Bone/Bone_Basics/

Reference: Bone Mineral Density in Young Women With Primary Ovarian Insufficiency: Results of a Three-Year Randomized Controlled Trial of Physiological Transdermal Estradiol and Testosterone Replacement. Popat VB, Calis KA, Kalantaridou SN, Vanderhoof VH, Koziol D, Troendle JF, Reynolds JC, Nelson LM. J Clin Endocrinol Metab. 2014 Jun 6:jc20134145. [Epub ahead of print]. PMID: 24905063.

Funding: NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and Procter & Gamble.

In about 90% of cases, the exact cause of POI is a mystery.^1,2,3

Research shows that POI is related to problems with the follicles (pronounced FOL-i-kulz)—the small sacs in the ovaries in which eggs grow and mature.³

Follicles start out as microscopic seeds called primordial (pronounced prahy-MAWR-dee-uhl) follicles. These seeds are not yet follicles, but they can grow into them. Normally, a woman is born with approximately 2 million primordial follicles,⁴ typically enough to last until she goes through natural menopause, usually around age 50.²

For a woman with POI, there are problems with the follicles:⁵

• Follicle depletion. A woman with follicle depletion runs out of working follicles earlier than normal or expected. In the case of POI, the woman runs out of working follicles before natural menopause occurs around age 50. Presently there is no safe way for scientists today to make primordial follicles.
• Follicle dysfunction. A woman with follicle dysfunction has follicles remaining in her ovaries, but the follicles are not working properly. Scientists do not have a safe and effective way to make follicles start working normally again.³

Although the exact cause is unknown in a majority of cases, some causes of follicle depletion and dysfunction have been identified:

• Genetic and chromosomal disorders. Disorders such as Fragile X syndrome and Turner syndrome can cause follicle depletion.^3,4,6
• Low number of follicles. Some women are born with fewer primordial follicles, so they have a smaller pool of follicles to use throughout their lives. Even though only one mature follicle releases an egg each month, less mature follicles usually develop along with that mature follicle and egg. Scientists don't understand exactly why this happens, but these "supporting" follicles seem to help the mature follicle function normally. If these extra follicles are missing, the main follicle will not mature and release an egg properly.
• Autoimmune diseases. Typically, the body's immune cells protect the body from invading bacteria and viruses. However, in autoimmune diseases, immune cells turn on healthy tissue. In the case of POI, the immune system may damage developing follicles in the ovaries. It could also damage the glands that make the hormones needed for the ovaries and follicles to work properly. Recent studies suggest that about 20% of women with POI have an autoimmune disease.^2,7
  • Thyroiditis (pronounced thahy-roi-DAHY-tis) is the autoimmune disorder most commonly associated with POI.⁷ It is an inflammation of the thyroid gland, which makes hormones that control metabolism, or the pace of body processes.
  • Addison's disease is also associated with POI. Addison's disease affects the adrenal glands, which produce hormones that help the body respond to physical stress, such as illness and injury; the hormones also affect ovary function.⁸ About 3% of women with POI have Addison's disease.⁹
• Chemotherapy or radiation therapy. These strong treatments for cancer may damage the genetic material in cells, including follicle cells.^1,3,10
• Metabolic disorders. These disorders affect the body's ability to create, store, and use the energy it needs. For example, galactosemia (pronounced guh-lak-tuh-SEE-mee-uh) affects how your body processes galactose (guh-LAK-tohs), a type of sugar. More than 80% of women and girls with galactosemia also have POI.⁷
• Toxins. Cigarette smoke, chemicals, and pesticides can speed up follicle depletion. In addition, viruses have been shown to affect follicle function.^2,4

---

1. Kodaman, P. H. (2010). Early menopause: Primary ovarian insufficiency and surgical menopause. Seminars in Reproductive Medicine, 28, 360–369.[top]
2. Nelson, L. M. (2009). Primary ovarian insufficiency. New England Journal of Medicine, 360, 606–614.[top]
3. De Vos, M., Devroey, P., & Fauser, B. C. (2010). Primary ovarian insufficiency. Lancet, 376, 911–921.[top]
4. Welt, C. K. (2008). Primary ovarian insufficiency: A more accurate term for premature ovarian failure.Clinical Endocrinology, 68, 499–509.[top]
5. American Congress of Obstetricians and Gynecologists. (2009). Premature ovarian failure: ACOG medical student teaching module [PowerPoint slides]. Retrieved January 3, 2012, fromhttp://classic.acog.org/acog_districts/dist_notice.cfm?recno=17&bulletin=2720  [top]
6. Cordts, E. B., Christofolini, D. M., Dos Santos, A. A., Bianco, B., & Barbosa, C. P. (2011). Genetic aspects of premature ovarian failure: A literature review. Archives of Gynecology and Obstetrics, 283, 635–643.
7. Rebar, R. W. (2009). Premature ovarian failure. Obstetrics and Gynecology, 113, 1355–1363.[top]
8. National Center for Biotechnical Information. (2009). Addison's disease. Retrieved January 12, 2012, fromhttp://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001416/ [top]
9. Eunice Kennedy Shriver National Institute of Child Health and Human Development. (2003). Premature ovarian failure. Retrieved January 4, 2012. [top]
10. National Library of Medicine. (2011). Premature ovarian failure. Retrieved January 4, 2012, fromwww.nlm.nih.gov/medlineplus/prematureovarianfailure.html [top]