Does estrogen cause secondary amenorrhea?

Does Estrogen Cause Secondary Amenorrhea?

No, low estrogen levels are typically associated with secondary amenorrhea rather than estrogen causing it. In fact, estrogen deficiency is a common finding in women with secondary amenorrhea, particularly in those with functional hypothalamic amenorrhea.

Relationship Between Estrogen and Amenorrhea

• Secondary amenorrhea is often characterized by systemic reductions in estradiol levels, not excess estrogen 1
• Low energy availability (EA) disrupts the hypothalamic-pituitary-gonadal (HPG) axis, leading to disruptions in luteinizing hormone (LH) pulsatility, which in turn causes menstrual dysfunction manifesting as oligo-amenorrhea 1
• These hormonal disruptions result in decreased estradiol and progesterone levels, not increased levels 1

Common Causes of Secondary Amenorrhea

• Functional Hypothalamic Amenorrhea (FHA) accounts for 20-35% of secondary amenorrhea cases and is characterized by low estrogen levels 2
• Polycystic Ovary Syndrome (PCOS) is another common cause of secondary amenorrhea but is typically associated with hormonal imbalances including elevated androgens rather than estrogen excess 2
• Hyperprolactinemia accounts for approximately 20% of secondary amenorrhea cases 2
• Primary Ovarian Insufficiency (POI) is characterized by elevated FSH and LH levels with low estrogen 2

Female Athlete Triad and RED-S

• In female athletes, the well-established female athlete triad involves perturbations of energy availability, bone health, and menstrual status 1
• Low energy availability causes disruptions of LH pulsatility, which disturbs gonadotropin release, resulting in menstrual dysfunction 1
• These hormonal changes include decreased estradiol, decreased progesterone, decreased leptin, increased ghrelin, and other hormonal alterations 1
• When estrogen levels are aberrantly subphysiologic (not elevated), osteoclast activity predominates and bone mass is lost 1

Treatment Approaches

• For women with secondary amenorrhea who have normal estrogen levels but are not menstruating, progesterone therapy may be used to induce withdrawal bleeding 3
• For women with secondary amenorrhea due to low estrogen levels, estrogen replacement therapy may be necessary 1
• Amenorrhea in contraceptive implant users is generally not harmful and does not require medical treatment 1
• Treatment of hypogonadism aims to normalize ovarian hormone levels through estrogen replacement with oral, micronized, or transdermal preparations 1

Diagnostic Considerations

• Initial laboratory evaluation for secondary amenorrhea should include serum FSH, LH, prolactin, and TSH levels 2
• Different patterns of LH, FSH, and estradiol can help classify the type of secondary amenorrhea 4
• Patients with hypothalamic-pituitary failure typically have low or low-normal levels of LH, FSH, and low estradiol 4

Clinical Implications

• Secondary amenorrhea with low estrogen levels increases risk for decreased bone mineral density and stress fractures 1
• In the setting of oligo-amenorrhea with low estrogen, bone microarchitecture is negatively affected, leading to decreased trabecular number and cortical thickness 1
• These changes result in decreased stiffness and lower failure load, ultimately increasing the incidence of bone stress injury 1

In summary, estrogen deficiency rather than excess is typically associated with secondary amenorrhea, particularly in cases related to functional hypothalamic amenorrhea, female athlete triad, and primary ovarian insufficiency.