Sign up for our monthly newsletter and stay up to date on all things menstrual and ovarian health. Newsletter

Ask An Expert: Catherine M. Gordon, MD, MS

  • April 28, 2023
  • Colleen Fisher

Senior Faculty, USDA/ARS Children’s Nutrition Research Center

Professor of Pediatrics, Baylor College of Medicine

Q: What are the common symptoms and signs of Primary Ovarian Insufficiency (POI) in teenagers, and how can they be distinguished from normal variations in menstrual cycles during puberty?

A: Adolescents with POI commonly present with infrequent or absent menses for four or more months. There is growing consensus that while adolescents can experience an irregular menstrual cycle during the first year after menarche, a young woman’s cycle should normalize within one to two years. It’s a myth that “anything goes” with respect to the menstrual cycle in adolescents. While the average cycle length (i.e., days between periods) is 28 days, a normal cycle ranges from 23-35 days. Concern should be raised when there is the trend of persistently long cycles and even more concern when an adolescent has four or fewer menses per year. Increasingly irregular menses can reflect the waxing and waning of ovarian function and should be investigated right away. Lastly, young adolescents with POI can present with growth and/or pubertal arrest or delay, and fatigue is an almost universal feature reflecting estradiol deficiency.

Q: What are the potential causes of Primary Ovarian Insufficiency (POI) in teenagers, and how can they be diagnosed? What tests or evaluations are typically recommended for teenage patients suspected of having POI?

A: Causes of POI can be grouped into a few categories: Genetic or chromosomal abnormalities (e.g., Turner syndrome or mosaic, carriage of FMR1 gene); autoimmune (including oophoritis as part of an autoimmune polyglandular syndrome); iatrogenic (e.g., long-term effects of chemotherapy or radiation for a malignancy); metabolic or infectious (e.g., galactosemia, infections – mumps, TB, CMV, HSV, etc.); and most commonly, idiopathic (diagnosis of exclusion after organic etiologies are ruled out). POI is diagnosed by obtaining two follicle stimulating hormone (FSH) measurements at least 30 days apart which are found to be elevated and in a menopausal range. Additional testing includes obtaining serum estradiol, free T4, thyroid stimulating hormone, and prolactin measurements, a karyotype, FMR1 testing, and a pelvic ultrasound. For those patients with suspected autoimmunity, additional testing includes: complete blood count, electrolytes, calcium, phosphorus, and morning cortisol, and antibodies to the thyroid (antithyroglobulin and antithyroid peroxidase) and adrenal glands (21-hydroxylase).

Q: What are the long-term health implications of Primary Ovarian Insufficiency (POI) in teenagers, both in terms of physical health (e.g., bone health) and emotional wellness (e.g., fertility concerns, psychological impact)? How can clinicians support teenagers with POI in managing these potential health concerns?

A: POI represents a condition of estradiol deficiency that can be linked to long-term comorbidities. Estradiol is important for healthy pubertal development, reproductive functioning and also for aspects of general or physical health (including skeletal, cardiovascular, sexual, and cognitive health). Patients with POI as part of an autoimmune polyglandular syndrome may also develop other endocrine deficiencies such as hypothyroidism, adrenal insufficiency, and hypoparathyroidism. One of the major concerns is that a diagnosis of POI during adolescence can compromise bone accrual and the attainment of peak bone mass, predisposing a young woman for the development of early osteoporosis. Untreated POI may also be linked to the early development of cardiovascular disease, dementia, and Parkinson disease. In addition to the issues affecting physical health, a diagnosis of POI is difficult emotionally for both a young adolescent, as well as her family. An endocrinologist or gynecologist will need to order a number of screening tests and prescribe estradiol replacement therapy as part of a physiologic hormone replacement strategy (see below) to keep a patient healthy. Equally important is the skill of a social worker or psychologist who can monitor an adolescent’s emotional health and be available to provide extra support. The diagnosis of any unexpected chronic condition can be overwhelming. Access to an endocrinologist with expertise in reproductive hormones (pediatric, medical, or reproductive endocrinologist)) is helpful even for young adolescents and their families who may have many questions. An integrated multi-pronged management approach is optimal to address both physical and emotional health.

Q: What are the available management options for Primary Ovarian Insufficiency (POI) in teenagers, and how do they differ from those for adult women with POI? What factors should be considered when deciding on the most appropriate management approach for a teenager with POI?

A: To avoid physical comorbidities, hormone replacement therapy (with physiologic estradiol replacement) is the mainstay of therapy. What is different in the treatment of adolescents is a gradual progression of estradiol dose, since some adolescents have not yet completed pubertal development and growth when they develop POI. Estradiol is associated with closure of the growth plates (also called epiphyses); thus a clinician must slowly titrate the dose, eventually prescribing progestogen in addition (12 days of the month) or as an intrauterine device (IUD) to deliver a progestogen to the uterine lining. The factors that are most important to consider are the age and pubertal stage of the adolescent at diagnosis; whether the adolescent is pre- or postmenarchal; the height and predicted final height of the patient; and how quickly the patient desires pubertal development and/or menses. Those patients who have an APS will also need to receive replacement therapy related to additional hormonal deficits (e.g., thyroid hormone, glucocorticoids, mineralocorticoid, etc.) and are best managed under the care of an experienced pediatric endocrinologist. Shared decision making with a patient and her family would be the goal for determining the treatment course, whenever possible.

Q: What are the implications of Primary Ovarian Insufficiency (POI) in teenagers regarding fertility? What are the potential options for preserving fertility in teenagers with POI, and what should be taken into consideration when discussing these options with adolescents with POI and their families?

A: Most patients have a low number of ovarian follicles remaining in the ovaries at the time of their diagnosis. Many POI experts are on a mission to raise awareness about how this relatively rare diagnosis can present so that more options are available with respect to family at the time of diagnosis. Fertility can vary, especially initially in the course of POI, reflecting waxing and waning ovarian function. Contraception is almost always recommended for adolescents as pregnancy is typically unwanted in this age group. Additionally, while most adolescents are not contemplating immediately starting a family, fertility ranks high among the worries of adolescents with this diagnosis. It is important to individualize care around fertility concerns for adolescents and their families. Identifying an expanded number of family planning options is the subject of fervent and exciting research. Options currently include: awaiting spontaneous pregnancy, child-free living, adoption, foster children, oocyte donation, embryo donation, and both cryopreservation and ovarian activation, the latter which are still under investigation. Lastly, evaluation of the emotional health of a young woman and her family is important, and connecting them with a psychotherapist (i.e.., social worker, psychologist or psychiatrist) is important if significant anxiety or depression is identified. 

Dr. Gordon is a pediatrician with dual training in adolescent medicine and pediatric endocrinology. She has a longtime interest in bone health and reproductive endocrinology. She is on the senior faculty at the USDA/ARS Children’s Nutrition Research Center and Professor of Pediatrics at the Baylor College of Medicine (BCM). For the past two decades, she has led an independently funded adolescent health research group with support from the NIH, the Department of Defense, and private foundations. She is interested in modifiable factors during adolescence that influence bone density and other aspects of health during the adult years, and ways to optimize the transition of healthcare from pediatric to adult medical care. Diseases her group has studied include POI, anorexia nervosa, endometriosis, and inflammatory bowel disease. Importantly, she has a special interest clinically in young women’s health, including care for adolescents and young women with POI.

Menstrual and Ovarian Health

Follow the Evidence

POI Fast Facts

POI is a hormonal deficiency. It is not menopause.

Read More

Know Your Numbers

Understanding estradiol deficiency begins with understanding ovarian hormones.

Read More

The Evidence

Research can help you make evidence-based decisions.

Read More

Think Again

Educate and advocate. Your doctor may not be an expert.

Read More