Causes
A variety of conditions can lead to hypoestrogenism: menopause is the most common. Primary ovarian insufficiency (premature menopause) due to varying causes, such as radiation therapy, chemotherapy, or a spontaneous manifestation, can also lead to low estrogen and infertility.Hypogonadism (a condition where the gonads – testes for men and ovaries for women – have diminished activity) can decrease estrogen. In primary hypogonadism, elevated serum gonadotropins are detected on at least two occasions several weeks apart, indicating gonadal failure. In secondary hypogonadism (where the cause is hypothalamic or pituitary dysfunction) serum levels of gonadotropins may be low.Other causes include certain medications, gonadotropin insensitivity, inborn errors of steroid metabolism (for example, aromatase deficiency, 17α-hydroxylase deficiency, 17,20-lyase deficiency, 3β-hydroxysteroid dehydrogenase deficiency, and cholesterol side-chain cleavage enzyme or steroidogenic acute regulatory protein deficiency) and functional amenorrhea. Risks
Low endogenous estrogen levels can elevate the risk of cardiovascular disease in women who reach early menopause. Estrogen is needed to relax arteries using endothelial-derived nitric oxide resulting in better heart health by decreasing adverse atherogenic effects. Women with POI may have an increased risk of cardiovascular disease due to low estrogen production. Pathophysiology
Estrogen deficiency has both vaginal and urologic effects; the female genitalia and lower urinary tract share common estrogen receptor function due to their embryological development. Estrogen is a vasoactive hormone (one that affects blood pressure) which stimulates blood flow and increases vaginal secretions and lubrication. Activated estrogen receptors also stimulate tissue proliferation in the vaginal walls, which contribute to the formation of rugae.
This rugae aids in sexual stimulation by becoming lubricated, distended, and expanded.Genitourinary effects of low estrogen include thinning of the vaginal epithelium, loss of vaginal barrier function, decrease of vaginal folding, decrease of the elasticity of the tissues, and decrease of the secretory activity of the Bartholin glands, which leads to traumatization of the vaginal mucosa and painful sensations. This thinning of the vaginal epithelium layers can increase the risk of developing inflammation and infection, such as urinary tract infection.The vagina is largely dominated by bacteria from the genus Lactobacillus, which typically comprise more than 70% of the vaginal bacteria in women. These lactobacilli process glycogen and its breakdown products, which result in a maintained low vaginal pH. Estrogen levels are closely linked to lactobacilli abundance and vaginal pH, as higher levels of estrogen promote thickening of the vaginal epithelium and intracellular production of glycogen. This large presence of lactobacilli and subsequent low pH levels are hypothesized to benefit women by protecting against sexually transmitted pathogens and opportunistic infections, and therefore reducing disease risk. Diagnosis
Hypoestrogenism is typically found in menopause and aids in diagnosis of other conditions such as POI and functional amenorrhea. Estrogen levels can be tested through several laboratory tests: vaginal maturation index, progestogen challenge test, and vaginal swabs for small parabasal cells. Menopause
Menopause is usually diagnosed through symptoms of vaginal atrophy, pelvic exams, and taking a comprehensive medical history consisting of last menstruation cycle.