Approach to the Patient With New-Onset Secondary Amenorrhea: Is This Primary Ovarian Insufficiency?

Abstract

Menstrual cyclicity is a marker of health for reproductively mature women. Absent menses, or amenorrhea, is often the initial sign of pregnancy—an indication that the system is functioning appropriately and capable of generating the intended evolutionary outcome. Perturbations of menstrual regularity in the absence of pregnancy provide a marker for physiological or pathological disruption of this well-orchestrated process. New onset amenorrhea with duration of 3 - 6 months should be promptly evaluated. Secondary amenorrhea can reflect structural or functional disturbances occurring from higher centers in the hypothalamus to the pituitary, the ovary and finally, the uterus. Amenorrhea can also be a manifestation of systemic disorders resulting in compensatory inhibition of reproduction. Identifying the point of the breakdown is essential to restoring reproductive homeostasis to maintain future fertility and reestablish reproductive hormonal integrity. Among the most challenging disorders contributing to secondary amenorrhea is primary ovarian insufficiency (POI). This diagnosis stems from a number of possible etiologies, including autoimmune, genetic, metabolic, toxic, iatrogenic, and idiopathic, each with associated conditions and attendant medical concerns. The dual assaults of unanticipated compromised fertility concurrently with depletion of the normal reproductive hormonal milieu yield multiple management challenges. Fertility restoration is an area of active research, while optimal management of estrogen deficiency symptoms and the anticipated preventive benefits of hormone replacement for bone, cardiovascular, and neurocognitive health remain understudied. The state of the evidence for an optimal, individualized, clinical management approach to women with POI is discussed along with priorities for additional research in this population.

Nuclear Estrogen Receptors in Prostate Cancer: From Genes to Function

“…Finally, the placenta produces estrogens during pregnancy, primarily estriol and estradiol, by aromatizing fetal steroids of an adrenal origin [ 17 , 18 ]. A deficit of estrogens may lead to a range of symptoms [ 19 , 20 ] at different grades that, at the level of the ovary, may be identified as an irregular menstrual cycle or amenorrhea [ 21 , 22 , 23 ]. Also, a deficit of estrogens is classically associated with an impaired bone metabolism and increased risk of osteoporosis [ 24 ], since these hormones regulate bone cell functions and the remodeling of this tissue [ 25 , 26 ].…”

Juvenile idiopathic arthritis and primary ovarian failure: a two-sample Mendelian randomization analysis in a mixed-gender cohort

“…The systemic decline in estrogen levels prior to natural menopause has been associated with osteoporosis, cardiovascular disease, and potentially hastened neurodegenerative aging ( 1 ). Currently, approximately 70% of primary ovarian failure can be attributed to genetic factors, including Turner syndrome (X chromosome loss) and chimerism, which are recognized as etiological factors for primary ovarian insufficiency ( 2 , 3 ). Additionally, autoimmune diseases account for 10%-30% of patients with primary ovarian failure, encompassing conditions such as autoimmune thyroid disease, Addison’s disease, and type 1 diabetes ( 4 ).…”

Retrospective Analysis of Effective Management Strategies for Primary Amenorrhea of Reproductive Age in Saudi Arabia

“…Furthermore, hormonal imbalances can also manifest as symptoms such as hot flashes, vaginal dryness, and mood disturbances, negatively impacting quality of life. Thus, addressing the hormonal disruptions associated with primary amenorrhea is essential not only for reproductive health but also for overall well-being and long-term health outcomes [ 34 , 35 ].…”