(21) Case report: Premature ovarian insufficiency as a cause of primary amenorrhea

Background: Premature ovarian insufficiency (POI) is the loss of ovarian function in women under 40 years, diagnosed through amenorrhea or oligomenorrhea and two elevated follicle-stimulating hormone (FSH) levels. Its prevalence ranges from 1% to 3.7%, with 1 in 10,000 cases in women under 20 years. In 70-90% of cases the etiology is unknown. Known causes include Turner syndrome, fragile X syndrome, autoimmunity, infections and iatrogenic. Untreated POI can lead to osteoporosis, cardiovascular risk, Alzheimer’s disease, mental health disorders and infertility. We present a case of POI manifesting as primary amenorrhea, with the aim of emphasizing the need of early identification and treatment.

Case: A 16-year-old girl with no prior medical history presented with primary amenorrhea. Her physical exam showed a height of 172 cm, 10 cm above her target height. She had Tanner stage 2 in breasts and pubic hair, anatomically normal female external genitalia and hypoestrogenized mucous membranes. Lab tests showed FSH levels of 69 mIU/ml and undetectable anti-Müllerian hormone. The gynecological ultrasound indicated uterine length of 52 mm and ovarian volumes of less than 1cc. POI was suspected and confirmed with a second elevated FSH level. Investigations into possible etiologies were carried out, revealing a 46 XX karyotype, negative fragile X premutation studies, normal thyroid function and negative thyroid antibodies. A genetic evaluation was requested, which included testing for 53 genes in Disorders of Sexual Development Panels, all of which were negative. Additionally, to rule out the diagnosis of Triple X syndrome, which can cause tall stature and POI, an extended karyotype with 50 metaphases was requested, and the result is pending. Due to prolonged hypoestrogenism, a bone densitometry was performed, with normal results.
The patient began low-dose transdermal estradiol, gradually increasing to 2 mg over two years, after which she had her first menstrual bleed. Monthly cyclic micronized progesterone was added. During treatment, she progressed to Tanner stage 5 for breast and pubic hair development, and her final height was 175 cm. Serial ultrasounds indicated progressive uterine growth, reaching 77 mm by age 20.

Comments: POI is a very rare diagnosis in women under 20 years, especially as a cause of primary amenorrhea. In our case, the patient presented arrested puberty at Tanner stage 2. While the cause is often unknown, ruling out common causes and monitoring for conditions like osteoporosis is crucial. Hormonal treatment should always be initiated promptly and continued until the average age of menopause to prevent hypoestrogenism-related complications.