Primer Offers Pearls on Pediatric Primary Ovarian Insufficiency

MIAMI BEACH – "Primary ovarian insufficiency: it’s not menopause!"

So began a primer on the important ways in which affected girls and adolescents can be diagnosed and managed, and importantly, counseled about their future with primary ovarian insufficiency.

"The sequelae of primary ovarian insufficiency are almost shocking," Dr. Beth W. Rackow said. Ovarian function is potentially lost decades before menopause. Diagnosis and long-term monitoring are important because primary ovarian insufficiency (POI) can cause adverse effects on skeletal metabolism, lipid profiles, insulin sensitivity, and endothelial dysfunction, which in turn can potentiate atherosclerosis and cardiovascular disease.

The timing of POI presentation varies – some girls will present before puberty, some with stalled puberty, and others after puberty, Dr. Rackow said at the annual meeting of the North American Society for Pediatric and Adolescent Gynecology. Unlike in menopause, ovarian dysfunction may not be permanent, which is why the term "ovarian insufficiency" is preferred to "ovarian failure," she added.

"It’s very likely you will see women with POI in your practice," Dr. Rackow said. Incidence increases with age, affecting about 1 in 10,000 girls and adolescents by age 20 years; 1 in 1,000 women by age 30; and 1 in 250 by age 35. Overall, about 1% of women will develop POI, she added.

Consider initially sharing a POI diagnosis face to face with parents before you talk to the child "so there is not global shock in the room," Dr. Rackow said. "They can support the child because they already know the diagnosis. They may also have insight into how their child will react." Explain why POI occurs, its impact on future fertility, and management options.

Although there is a genetic component to POI, the etiology for 90% of cases can be unclear, making this a challenging diagnosis. "We often don’t have a reason why a girl is presenting with this condition," said Dr. Rackow, a reproductive endocrinologist who is board certified in pediatric and adolescent gynecology within the department of clinical obstetrics & gynecology at New York Presbyterian Hospital/Columbia University Medical Center.

Follicle depletion and follicle dysfunction are the two main mechanisms. Depletion can stem from a lower baseline number of primordial follicles – "they start with less" – and/or from an increased rate of atresia. Follicle dysfunction, on the other hand, can result from impaired folliculogenesis or inappropriate luteinization that leads, over time, to a decreased complement or complete absence of oocytes.

Future fertility will be a leading concern. The spontaneous pregnancy rate for women with POI is 5%-10%. Some may consider in vitro fertilization or fertility assistance, but a poor to no response to gonadotropins "makes going through fertility treatment very challenging," Dr. Rackow said. There are many options for these patients to have a family, she added, including use of donor oocytes, donated embryos, and adoption. She sometimes tells patients: "You will be a mom someday. It just may be through a different way than you thought."

Psychological support can help patients and families after a diagnosis of POI. Dr. Rackow recommended two websites with more information: IPOFA & Rachel’s Well.

Menstrual anomalies could be your first clue. "Girls who have some abnormal menses for 3 months or more probably deserve further work-up," Dr. Rackow said. Also ask about pubertal history; any prior ovarian surgery, chemotherapy, or radiation; and their medical history because 20% of affected women have autoimmune disease. In addition, about 25% of girls with POI will have a thyroid disorder, but the 3% with adrenal disorders are particularly important to identify quickly. Consider checking the patient for adrenocortical antibodies, which in a girl with POI can point to significantly elevated risk for adrenal insufficiency. "They can get very sick with autoimmune adrenal failure."

In addition to an autoimmune work-up, "clearly we are going to get a karyotype on these patients," Dr. Rackow said. An estimated 6%-14% of women with POI carry a FMR-1 mutation, for example. X chromosome abnormalities, including trisomy X, are also possible.

Useful laboratory assays include measures of human chorionic gonadotropin and follicle stimulating hormone plus estradiol levels. "We tend to see low estradiol ... a sign of no estrogen production from the ovaries," Dr. Rackow said. "Normally, estrogen suppresses FSH more than luteinizing hormone, but in POI you tend to see elevated FSH."

Pelvic ultrasound to check for any antral follicles or any endometrium build-up also can be helpful. Bone densitometry also is helpful as a baseline measure after the POI diagnosis. "The bones can take a significant hit from POI in terms of bone density," Dr. Rackow said.

Following diagnosis of POI, consider annual, routine surveillance for endocrine disorders. Test for complete blood count, complete metabolic panel, calcium, phosphorus, fasting glucose, insulin, thyroid stimulating hormone, and thyroid peroxidase antibodies.

Estrogen replacement is part of management of these patients. "They require higher doses than [do] menopausal women. Also, if you give estrogen, [they] will need progestins for endometrial protection," Dr. Rackow said. Hormone replacement therapy can improve endothelial function within 6 months, potentially improve their long-term cardiovascular health, and mitigate bone loss.

"The lowest dose oral contraceptives have the higher end dose of estrogen you would give for POI. These girls do not need more," Dr. Rackow said. For more information, including hormone replacement therapy dosing guidance, see the September 2011 American College of Obstetrics and Gynecology Committee Opinion No. 502 on primary ovarian insufficiency in the adolescent (Obstet. Gynecol. 2011;118:741-5).

Dr. Rackow said she had no relevant financial disclosures.

MIAMI BEACH – "Primary ovarian insufficiency: it’s not menopause!"

So began a primer on the important ways in which affected girls and adolescents can be diagnosed and managed, and importantly, counseled about their future with primary ovarian insufficiency.

"The sequelae of primary ovarian insufficiency are almost shocking," Dr. Beth W. Rackow said. Ovarian function is potentially lost decades before menopause. Diagnosis and long-term monitoring are important because primary ovarian insufficiency (POI) can cause adverse effects on skeletal metabolism, lipid profiles, insulin sensitivity, and endothelial dysfunction, which in turn can potentiate atherosclerosis and cardiovascular disease.

The timing of POI presentation varies – some girls will present before puberty, some with stalled puberty, and others after puberty, Dr. Rackow said at the annual meeting of the North American Society for Pediatric and Adolescent Gynecology. Unlike in menopause, ovarian dysfunction may not be permanent, which is why the term "ovarian insufficiency" is preferred to "ovarian failure," she added.

"It’s very likely you will see women with POI in your practice," Dr. Rackow said. Incidence increases with age, affecting about 1 in 10,000 girls and adolescents by age 20 years; 1 in 1,000 women by age 30; and 1 in 250 by age 35. Overall, about 1% of women will develop POI, she added.

Consider initially sharing a POI diagnosis face to face with parents before you talk to the child "so there is not global shock in the room," Dr. Rackow said. "They can support the child because they already know the diagnosis. They may also have insight into how their child will react." Explain why POI occurs, its impact on future fertility, and management options.

Although there is a genetic component to POI, the etiology for 90% of cases can be unclear, making this a challenging diagnosis. "We often don’t have a reason why a girl is presenting with this condition," said Dr. Rackow, a reproductive endocrinologist who is board certified in pediatric and adolescent gynecology within the department of clinical obstetrics & gynecology at New York Presbyterian Hospital/Columbia University Medical Center.

Follicle depletion and follicle dysfunction are the two main mechanisms. Depletion can stem from a lower baseline number of primordial follicles – "they start with less" – and/or from an increased rate of atresia. Follicle dysfunction, on the other hand, can result from impaired folliculogenesis or inappropriate luteinization that leads, over time, to a decreased complement or complete absence of oocytes.

Future fertility will be a leading concern. The spontaneous pregnancy rate for women with POI is 5%-10%. Some may consider in vitro fertilization or fertility assistance, but a poor to no response to gonadotropins "makes going through fertility treatment very challenging," Dr. Rackow said. There are many options for these patients to have a family, she added, including use of donor oocytes, donated embryos, and adoption. She sometimes tells patients: "You will be a mom someday. It just may be through a different way than you thought."

Psychological support can help patients and families after a diagnosis of POI. Dr. Rackow recommended two websites with more information: IPOFA & Rachel’s Well.

Menstrual anomalies could be your first clue. "Girls who have some abnormal menses for 3 months or more probably deserve further work-up," Dr. Rackow said. Also ask about pubertal history; any prior ovarian surgery, chemotherapy, or radiation; and their medical history because 20% of affected women have autoimmune disease. In addition, about 25% of girls with POI will have a thyroid disorder, but the 3% with adrenal disorders are particularly important to identify quickly. Consider checking the patient for adrenocortical antibodies, which in a girl with POI can point to significantly elevated risk for adrenal insufficiency. "They can get very sick with autoimmune adrenal failure."

In addition to an autoimmune work-up, "clearly we are going to get a karyotype on these patients," Dr. Rackow said. An estimated 6%-14% of women with POI carry a FMR-1 mutation, for example. X chromosome abnormalities, including trisomy X, are also possible.

Useful laboratory assays include measures of human chorionic gonadotropin and follicle stimulating hormone plus estradiol levels. "We tend to see low estradiol ... a sign of no estrogen production from the ovaries," Dr. Rackow said. "Normally, estrogen suppresses FSH more than luteinizing hormone, but in POI you tend to see elevated FSH."

Pelvic ultrasound to check for any antral follicles or any endometrium build-up also can be helpful. Bone densitometry also is helpful as a baseline measure after the POI diagnosis. "The bones can take a significant hit from POI in terms of bone density," Dr. Rackow said.

Following diagnosis of POI, consider annual, routine surveillance for endocrine disorders. Test for complete blood count, complete metabolic panel, calcium, phosphorus, fasting glucose, insulin, thyroid stimulating hormone, and thyroid peroxidase antibodies.

Estrogen replacement is part of management of these patients. "They require higher doses than [do] menopausal women. Also, if you give estrogen, [they] will need progestins for endometrial protection," Dr. Rackow said. Hormone replacement therapy can improve endothelial function within 6 months, potentially improve their long-term cardiovascular health, and mitigate bone loss.

"The lowest dose oral contraceptives have the higher end dose of estrogen you would give for POI. These girls do not need more," Dr. Rackow said. For more information, including hormone replacement therapy dosing guidance, see the September 2011 American College of Obstetrics and Gynecology Committee Opinion No. 502 on primary ovarian insufficiency in the adolescent (Obstet. Gynecol. 2011;118:741-5).

Dr. Rackow said she had no relevant financial disclosures.

MIAMI BEACH – "Primary ovarian insufficiency: it’s not menopause!"

So began a primer on the important ways in which affected girls and adolescents can be diagnosed and managed, and importantly, counseled about their future with primary ovarian insufficiency.

"The sequelae of primary ovarian insufficiency are almost shocking," Dr. Beth W. Rackow said. Ovarian function is potentially lost decades before menopause. Diagnosis and long-term monitoring are important because primary ovarian insufficiency (POI) can cause adverse effects on skeletal metabolism, lipid profiles, insulin sensitivity, and endothelial dysfunction, which in turn can potentiate atherosclerosis and cardiovascular disease.

The timing of POI presentation varies – some girls will present before puberty, some with stalled puberty, and others after puberty, Dr. Rackow said at the annual meeting of the North American Society for Pediatric and Adolescent Gynecology. Unlike in menopause, ovarian dysfunction may not be permanent, which is why the term "ovarian insufficiency" is preferred to "ovarian failure," she added.

"It’s very likely you will see women with POI in your practice," Dr. Rackow said. Incidence increases with age, affecting about 1 in 10,000 girls and adolescents by age 20 years; 1 in 1,000 women by age 30; and 1 in 250 by age 35. Overall, about 1% of women will develop POI, she added.

Consider initially sharing a POI diagnosis face to face with parents before you talk to the child "so there is not global shock in the room," Dr. Rackow said. "They can support the child because they already know the diagnosis. They may also have insight into how their child will react." Explain why POI occurs, its impact on future fertility, and management options.

Although there is a genetic component to POI, the etiology for 90% of cases can be unclear, making this a challenging diagnosis. "We often don’t have a reason why a girl is presenting with this condition," said Dr. Rackow, a reproductive endocrinologist who is board certified in pediatric and adolescent gynecology within the department of clinical obstetrics & gynecology at New York Presbyterian Hospital/Columbia University Medical Center.

Follicle depletion and follicle dysfunction are the two main mechanisms. Depletion can stem from a lower baseline number of primordial follicles – "they start with less" – and/or from an increased rate of atresia. Follicle dysfunction, on the other hand, can result from impaired folliculogenesis or inappropriate luteinization that leads, over time, to a decreased complement or complete absence of oocytes.

Future fertility will be a leading concern. The spontaneous pregnancy rate for women with POI is 5%-10%. Some may consider in vitro fertilization or fertility assistance, but a poor to no response to gonadotropins "makes going through fertility treatment very challenging," Dr. Rackow said. There are many options for these patients to have a family, she added, including use of donor oocytes, donated embryos, and adoption. She sometimes tells patients: "You will be a mom someday. It just may be through a different way than you thought."

Psychological support can help patients and families after a diagnosis of POI. Dr. Rackow recommended two websites with more information: IPOFA & Rachel’s Well.

Menstrual anomalies could be your first clue. "Girls who have some abnormal menses for 3 months or more probably deserve further work-up," Dr. Rackow said. Also ask about pubertal history; any prior ovarian surgery, chemotherapy, or radiation; and their medical history because 20% of affected women have autoimmune disease. In addition, about 25% of girls with POI will have a thyroid disorder, but the 3% with adrenal disorders are particularly important to identify quickly. Consider checking the patient for adrenocortical antibodies, which in a girl with POI can point to significantly elevated risk for adrenal insufficiency. "They can get very sick with autoimmune adrenal failure."

In addition to an autoimmune work-up, "clearly we are going to get a karyotype on these patients," Dr. Rackow said. An estimated 6%-14% of women with POI carry a FMR-1 mutation, for example. X chromosome abnormalities, including trisomy X, are also possible.

Useful laboratory assays include measures of human chorionic gonadotropin and follicle stimulating hormone plus estradiol levels. "We tend to see low estradiol ... a sign of no estrogen production from the ovaries," Dr. Rackow said. "Normally, estrogen suppresses FSH more than luteinizing hormone, but in POI you tend to see elevated FSH."

Pelvic ultrasound to check for any antral follicles or any endometrium build-up also can be helpful. Bone densitometry also is helpful as a baseline measure after the POI diagnosis. "The bones can take a significant hit from POI in terms of bone density," Dr. Rackow said.

Following diagnosis of POI, consider annual, routine surveillance for endocrine disorders. Test for complete blood count, complete metabolic panel, calcium, phosphorus, fasting glucose, insulin, thyroid stimulating hormone, and thyroid peroxidase antibodies.

Estrogen replacement is part of management of these patients. "They require higher doses than [do] menopausal women. Also, if you give estrogen, [they] will need progestins for endometrial protection," Dr. Rackow said. Hormone replacement therapy can improve endothelial function within 6 months, potentially improve their long-term cardiovascular health, and mitigate bone loss.

"The lowest dose oral contraceptives have the higher end dose of estrogen you would give for POI. These girls do not need more," Dr. Rackow said. For more information, including hormone replacement therapy dosing guidance, see the September 2011 American College of Obstetrics and Gynecology Committee Opinion No. 502 on primary ovarian insufficiency in the adolescent (Obstet. Gynecol. 2011;118:741-5).

Dr. Rackow said she had no relevant financial disclosures.