Premature menopause causes
Premature menopause is clinically evaluated as premature ovarian insufficiency (POI) when ovarian function loss occurs before age 40 with menopausal symptoms and biochemical confirmation. [1] The major POI cause categories include genetic/chromosomal conditions, autoimmune etiologies, and iatrogenic injury from medical or surgical treatment. [1]
Genetic and chromosomal causes
Chromosomal abnormalities are evaluated with karyotyping in non-iatrogenic POI. [1] Y-chromosomal material is evaluated because detectable Y material is associated with gonadal malignancy risk and gonadectomy is recommended when Y material is present. [1] Fragile X premutation (FMR1) is evaluated because it is an established cause of POI and testing includes pre-test counseling. [1]
Autoimmune causes
Adrenocortical autoimmunity is evaluated with testing for 21-hydroxylase antibodies (21OH-Ab) or alternatively adrenocortical antibodies (ACA) in POI of unknown cause or when an immune disorder is suspected. [1] If 21OH-Ab/ACA is positive, referral to endocrinology is recommended for adrenal function testing to rule out Addison’s disease. [1] Thyroid autoimmunity is evaluated with thyroid peroxidase antibodies (TPO-Ab) in POI of unknown cause or when an immune disorder is suspected. [1] If TPO-Ab is positive, thyroid-stimulating hormone (TSH) should be measured every year. [1]
Iatrogenic and related causes
The possibility of POI being a consequence of medical or surgical intervention is discussed as part of consent for those treatments. [1]
Initial diagnostic criteria for premature ovarian insufficiency
Diagnosis of POI in women aged under 40 is based on menopausal symptoms plus elevated FSH on two blood samples taken 4–6 weeks apart. [2] A single blood test should not be used to establish the diagnosis. [2] The ESHRE guideline diagnostic criteria similarly require oligo/amenorrhea for at least 4 months and FSH >25 IU/L on two occasions more than 4 weeks apart. [1]
Immediate laboratory evaluation
FSH is measured and repeated on a second occasion when the first test is elevated to meet diagnostic confirmation requirements. [1] Menopausal symptoms and menstrual history are used to select patients for biochemical testing. [2]
Differential diagnosis considerations before confirming POI
Changes in menstrual history are used to consider alternative diagnoses such as pregnancy and polycystic ovary syndrome, which should be considered during evaluation before diagnosis confirmation. [3]
Etiology workup after biochemical confirmation
Karyotyping is performed in non-iatrogenic POI. [1] FMR1 fragile X premutation testing is indicated in POI with appropriate genetic counseling and discussion of implications. [1] Autimmune testing is targeted to clinical context and cause uncertainty with 21OH-Ab/ACA and TPO-Ab when appropriate. [1] Routine infection screening is not indicated in POI. [1]
Common workup endpoints
A complete workup includes both diagnostic confirmation of POI and etiology assessment using genetic and targeted autoimmune investigations based on clinical context. [1]
References for diagnostic workup recommendations
NICE and ESHRE provide the core diagnostic criteria and confirmatory approach, including repeat FSH testing and targeted etiologic evaluation. [1] [2]