Primary ovarian insufficiency

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Primary ovarian insufficiency, or premature ovarian failure, is defined as ovarian failure before age 40 years. It is the scientifically accurate term for the condition that was previously referred to as premature menopause or premature ovarian failure. Other terms used for the condition include primary ovarian failure and hypergonadotropic hypogonadism, as well as the misnomer, gonadal dysgenesis.[1] The term "Primary Ovarian Insufficiency" was first used in 1942 by Fuller Albright who first described the condition.[1] Many consider him to be the father of modern endocrinology. The terms "Premature Menopause" and "Premature Ovarian Failure" are meant to imply that conception after the diagnosis is not possible. We now know that this is not true and that 5 to 10% of women with primary ovarian insufficiency conceive subsequent to the diagnosis without medical intervention.[2]

The ovaries play two important roles in maintaining a woman's health: 1) they are a source of important hormones, and 2) they are a storage place for eggs.


Endocrinology is the study of the system in our bodies that regulates our hormones. The Endocrinology of reproduction is the study of the bodily mechanisms of reproduction as a scientific endeavor. "Reproductive endocrinology and infertility" is a surgical subspecialty of Obstetrics and Gynecology that provides reproductive health care related primarily to the technical aspects of treating infertility.

Hormones are chemical messengers that circulate in the blood and in both men and women hormones play important roles in helping us to maintain our physical health as well as our emotional health. These chemical messages in our blood permit one part of the body to communicate with other parts of the body via the circulatory system. Hormones in the blood tell our cells what to do by acting on hormone receptors. The ovary is the main source of estradiol, the major estrogen in the body. There are estradiol hormone receptors in many parts of the body, such as in the skin, the hair, the bone, the brain, and blood vessels. The ovaries are also a source of small amounts of androgens, or male sex hormones, such as testosterone and androstenedione. Other hormones that come from the ovaries include inhibin and anti-mullerian hormone (AMH).

The ovaries are unique in the endocrine system in that they create an entirely new "gland" or secretory structure each month. This secretory structure is known as the graafian follicle. The graafian follicle arises from a tiny microscopic seed known as a primordial follicle. The primordial follicles must function normally in order for women to produce normal amounts of the major estradiol and to have regular menstrual cycles. These primordial follicles must also function normally for women to be able to release eggs from their ovaries in a process called ovulation. Menopause, defined as the permanent cessation of menstrual cycles, results from the depletion of potentially functional primordial follicles. The average age of natural menopause in normal women is approximately 50 years. Menopause before the age of 40 years is premature.

Hormone replacement therapy[edit]

Women younger than 40 years of age who have primary ovarian insufficiency benefit from physiologic replacement of the ovarian hormones they are missing.[1] Most authorities recommend that this hormone replacement continue until age 50 years, the normal age of menopause. The leading hormone replacement regimen recommended involves the administration of estradiol 100 micrograms per day by either skin patch or vaginal ring. This approach reduces the risk of pulmonary embolism and deep venous thrombosis by avoiding the first pass effect on the liver that is induced by oral estrogen therapy.[1] To avoid the development of endometrial cancer young women taking estradiol replacement need also to take a progestin in a regular cyclic fashion. The most evidence supports the use of 10 milligrams of medroxyprogesterone acetate per day for days one through 12 of each calendar month.[1] This will induce regular and predictable menstrual cycles. It is important that women taking this regimen keep a menstrual calendar. If the next expected menses is late it is important to get a pregnancy test. It this is positive, the woman should stop taking the hormone replacement. Approximately 5 to 10% of women with confirmed primary ovarian insufficiency conceive a pregnancy after the diagnosis without medical intervention.[1]

Emotional health[edit]

The most common words women use to describe how they felt in the 2 hours after being given the diagnosis of primary ovarian insufficiency are "devastated, "shocked," and "confused."[3] These are words that describe emotional trauma. The diagnosis is more than infertility and affects a woman’s physical and emotional well-being.[1] Patients face the acute shock of the diagnosis, associated stigma of infertility, grief from the death of dreams, anxiety and depression from the disruption of life plans, confusion around the cause, symptoms of estrogen deficiency, worry over the associated potential medical sequelae such as reduced bone density and cardiovascular risk, and the uncertain future that all of these factors create. There is a need for an evidence-based integrative medicine program to assist women with primary ovarian insufficiency.[4] Presently such a program does not exist in the community, but a community of practice has formed to address this deficiency.[4] Women with primary ovarian insufficiency perceive lower social support than control women, so building a trusted community of practice for them would be expected to improve their well being.[5][6][7][8] It is important to connect women with primary ovarian insufficiency to an appropriate collaborative care team because the condition has been clearly associated with suicide related to the stigma of infertility.[7] Suicide rates are know to be increased in women who experience infertility.[9] There is no evidence that online support groups or support groups that are not supervised by qualified professionally trained mental health providers benefit women with this condition. There is a risk that other patients with personality disorders can join these groups and harm vulnerable patients in the early stages of dealing with this disorder. There is a need for more research in the area of emotional support for these women.


  1. ^ a b c d e f g Nelson, Lawrence M. (2009). "Primary Ovarian Insufficiency". New England Journal of Medicine 360 (6): 606–14. doi:10.1056/NEJMcp0808697. PMC 2762081. PMID 19196677. 
  2. ^ Van Kasteren, Y.; Schoemaker, J (1999). "Premature ovarian failure: A systematic review on therapeutic interventions to restore ovarian function and achieve pregnancy". Human Reproduction Update 5 (5): 483–92. doi:10.1093/humupd/5.5.483. PMID 10582785. 
  3. ^ Groff, Allison A.; Covington, Sharon N.; Halverson, Lynn R.; Fitzgerald, O. Ray; Vanderhoof, Vien; Calis, Karim; Nelson, Lawrence M. (2005). "Assessing the emotional needs of women with spontaneous premature ovarian failure". Fertility and Sterility 83 (6): 1734–41. doi:10.1016/j.fertnstert.2004.11.067. PMID 15950644. 
  4. ^ a b Cooper, Amber R.; Baker, Valerie L.; Sterling, Evelina W.; Ryan, Mary E.; Woodruff, Teresa K.; Nelson, Lawrence M. (2011). "The time is now for a new approach to primary ovarian insufficiency". Fertility and Sterility 95 (6): 1890–7. doi:10.1016/j.fertnstert.2010.01.016. PMC 2991394. PMID 20188353. 
  5. ^ Orshan, Susan A.; Ventura, June L.; Covington, Sharon N.; Vanderhoof, Vien H.; Troendle, James F.; Nelson, Lawrence M. (2009). "Women with spontaneous 46,XX primary ovarian insufficiency (hypergonadotropic hypogonadism) have lower perceived social support than control women". Fertility and Sterility 92 (2): 688–93. doi:10.1016/j.fertnstert.2008.07.1718. PMC 2734403. PMID 18829005. 
  6. ^ Nelson, Lawrence M.; Captain, U.S. Public Health Service (2011). "Synchronizing the world of women's health: Young Turks and transformational leaders report for duty". Fertility and Sterility 95 (6): 1902–. doi:10.1016/j.fertnstert.2011.03.009. PMC 3153063. PMID 21841843. 
  7. ^ a b Nelson, Lawrence M. (2011). "One world, one woman". Menopause 18 (5): 480–487. doi:10.1097/GME.0b013e318213f250. PMC 3115754. PMID 21686065. 
  8. ^ Sterling, Evelina; Nelson, Lawrence (2011). "From Victim to Survivor to Thriver: Helping Women with Primary Ovarian Insufficiency Integrate Recovery, Self-Management, and Wellness". Seminars in Reproductive Medicine 29 (4): 353. doi:10.1055/s-0031-1280920. 
  9. ^ Kjaer, T. K.; Jensen, A.; Dalton, S. O.; Johansen, C.; Schmiedel, S.; Kjaer, S. K. (2011). "Suicide in Danish women evaluated for fertility problems". Human Reproduction 26 (9): 2401–7. doi:10.1093/humrep/der188. PMID 21672927.