Causes of Low Estrogen

Primary Ovarian Causes

Natural menopause occurs between ages 46-55 years (median 51 years) when ovarian estrogen production ceases, as stated by the American College of Physicians and the American Academy of Family Physicians 1, 2
Oophorectomy is a documented cause of primary ovarian failure regardless of whether performed for cancer treatment or risk reduction, according to the American Society of Clinical Oncology 3
Alkylating chemotherapy agents and heavy metals cause dose-dependent ovarian failure, with risk directly correlated to cumulative dose and age at exposure, as reported by the American Society of Clinical Oncology 3
Ovarian radiation causes acute ovarian failure and premature ovarian failure, with doses as low as 5 Gy affecting ovarian function in postpubertal girls, according to the American Society of Clinical Oncology 3
Breast cancer treatment with aromatase inhibitors inhibits peripheral conversion of androgens to estrogens by >95%, causing severe estrogen deficiency, as stated by the European Society for Medical Oncology 4

Hypothalamic/pituitary damage from tumor, radiation, or surgery impairs release of GnRH, LH, and FSH, resulting in central hypogonadism, as reported by the American Society of Clinical Oncology 3
CNS radiation used to treat childhood cancers can adversely affect hormonal regulation, according to the American Society of Clinical Oncology 3

Energy deficit in female athletes causes disruptions of LH pulsatility, which disturbs GnRH pulsatility and gonadotropin release, leading to menstrual dysfunction and systemic reductions in estradiol, as stated by the International Federation of Sports Medicine 5, 6
Energy availability <30 kcal/kg FFM/day discriminates between amenorrheic vs. eumenorrheic status, according to the International Federation of Sports Medicine 5, 6

Advanced liver disease causes altered estrogen metabolism and disruption of the hypothalamic-pituitary axis with low FSH and LH, leading to anovulation, amenorrhea, and infertility in women with cirrhosis, as reported by the American Association for the Study of Liver Diseases 7, 8
Amenorrhea or oligomenorrhea occurs in >25% of women with advanced liver disease and nearly 75% of premenopausal women awaiting liver transplant, according to the American Association for the Study of Liver Diseases 7, 8

Do not assume menstruation indicates normal estrogen levels: Women with cirrhosis can still become pregnant despite menstrual irregularities, as stated by the American Association for the Study of Liver Diseases 7, 8
Premature menopause is often underdiagnosed: Women with POI before age 40 have substantially increased stroke risk and require hormone replacement until natural menopause age, according to the American Heart Association 9
Cancer survivors need long-term monitoring: Young survivors who ceased menstruating ≥5 years after diagnosis have acute ovarian failure requiring assessment, as reported by the American Society of Clinical Oncology 3