From the Guidelines
The cause of this patient's secondary amenorrhea is likely functional hypothalamic amenorrhea (FHA), a condition characterized by hypogonadotropic hypogonadism, as evidenced by her low FSH, LH, and oestradiol levels, and is often associated with stress, weight loss, and psychological disorders 1. The patient's presentation of low FSH, LH, and oestradiol levels is consistent with FHA, which is caused by a functional reduction in the frequency of the pulsatile secretion of GnRH, leading to a decline in the frequency of LH pulses and a reduction in serum LH and FSH levels 1. Some key points to consider in this patient's evaluation include:
- A detailed history regarding weight changes, excessive exercise, stress, and eating habits, as these factors are commonly associated with FHA 1
- Assessment of other pituitary hormones, such as prolactin, thyroid function tests, and ACTH, cortisol, and growth hormone levels to determine if there is a more generalized pituitary dysfunction
- Pregnancy testing to exclude pregnancy as a cause of amenorrhea
- Consideration of an MRI of the pituitary and hypothalamus to rule out structural lesions, although FHA is a more likely cause given the patient's presentation The patient's previous use of combined oral contraceptives is unlikely to be the cause of her current condition, as COC-related amenorrhea typically resolves within a few months of discontinuation and would not present with such profoundly suppressed gonadotropin levels. Further investigations and management should focus on addressing potential underlying causes of FHA, such as stress and weight loss, and considering hormone replacement therapy to alleviate symptoms and prevent long-term consequences of estrogen deficiency.
From the Research
Hypothalamic-Pituitary-Gonadal Axis Dysfunction
The cause of secondary amenorrhea in a 34-year-old female with hypogonadotropic hypogonadism and low oestradiol levels, who previously used Combined Oral Contraceptive (COC) pills, can be related to the dysfunction of the hypothalamic-pituitary-gonadal (HPG) axis.
- The HPG axis is regulated by a number of G protein-coupled receptors, including GnRH, LH, FSH, and GPR54 receptors 2.
- Hypogonadotropic hypogonadism is characterized by low levels of FSH and LH, which can be caused by a variety of factors, including hypothalamic or pituitary dysfunction 3, 4.
- The use of COC pills can also affect the HPG axis, leading to changes in gonadotropin and gonadal hormone levels 5.
Effect of Estrogen on the HPG Axis
Estrogen plays a crucial role in the regulation of the HPG axis, and changes in estrogen levels can affect gonadotropin secretion.
- In men, circulating estrogens are required at the hypothalamic level for the integrity of gonadotropin negative feedback 6.
- Estrogen treatment has been shown to reduce LH-pulsated frequency and amplitude, as well as FSH serum levels, in aromatase-deficient men 6.
- The administration of estrogen to aromatase-deficient men discloses the effects of circulating estrogens on LH secretion, exerted both at pituitary level and at hypothalamic level 6.
Potential Causes of Secondary Amenorrhea
Based on the available evidence, potential causes of secondary amenorrhea in this patient include:
- Hypothalamic or pituitary dysfunction, leading to hypogonadotropic hypogonadism 3, 4.
- Changes in estrogen levels, potentially related to the use of COC pills or other factors 6, 5.
- Dysfunction of the G protein-coupled receptors that regulate the HPG axis, including GnRH, LH, FSH, and GPR54 receptors 2.