Hypoestrogenism, or estrogen deficiency, refers to a lower than normal level of

estrogen Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...

. It is an umbrella term used to describe estrogen deficiency in various conditions. Estrogen deficiency is also associated with an increased risk of

cardiovascular disease Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina, heart attack), heart failure, hypertensive heart disease, rheumati ...

, and has been linked to diseases like

urinary tract infections A urinary tract infection (UTI) is an infection that affects a part of the urinary tract. Lower urinary tract infections may involve the bladder (cystitis) or urethra ( urethritis) while upper urinary tract infections affect the kidney (pye ...

and

osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to more porous bone, and consequent increase in Bone fracture, fracture risk. It is the most common reason f ...

. In women, low levels of estrogen may cause symptoms such as

hot flash Hot flushes are a form of flushing, often caused by the changing hormone levels that are characteristic of menopause. They are typically experienced as a feeling of intense heat with sweating and rapid heartbeat, and may typically last from t ...

es, sleeping disturbances, decreased bone health, and changes in the

genitourinary system The genitourinary system, or urogenital system, are the sex organs of the reproductive system and the organs of the urinary system. These are grouped together because of their proximity to each other, their common embryological origin and the u ...

. Hypoestrogenism is most commonly found in women who are

postmenopausal Menopause, also known as the climacteric, is the time when menstrual periods permanently stop, marking the end of the reproductive stage for the female human. It typically occurs between the ages of 45 and 55, although the exact timing can ...

, have

primary ovarian insufficiency Primary ovarian insufficiency (POI), also called premature ovarian insufficiency and premature ovarian failure, is the partial or total loss of reproductive and hormonal function of the ovaries before age 40 because of follicular (egg producing ...

(POI), or are presenting with

amenorrhea Amenorrhea or amenorrhoea is the absence of a menstrual period in a female organism who has reached reproductive age. Physiological states of amenorrhoea are most commonly seen during pregnancy and lactation (breastfeeding). In humans, it is wher ...

(absence of

menstrual periods The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that makes pregnancy possible. The ovarian cycle controls the production and release of egg ...

). Hypoestrogenism includes primarily genitourinary effects, including thinning of the

vagina In mammals and other animals, the vagina (: vaginas or vaginae) is the elastic, muscular sex organ, reproductive organ of the female genital tract. In humans, it extends from the vulval vestibule to the cervix (neck of the uterus). The #Vag ...

l tissue layers and an increase in

vaginal pH In mammal A mammal () is a vertebrate animal of the Class (biology), class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur ...

. With normal levels of estrogen, the environment of the vagina is protected against

inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...

infections An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...

, and

sexually transmitted infections A sexually transmitted infection (STI), also referred to as a sexually transmitted disease (STD) and the older term venereal disease (VD), is an infection that is spread by sexual activity, especially vaginal intercourse, anal sex, or ...

. Hypoestrogenism can also occur in men, for instance due to

hypogonadism Hypogonadism means diminished functional activity of the human gonad, gonads—the testicles or the ovary, ovaries—that may result in diminished biosynthesis, production of sex hormones. Low androgen (e.g., testosterone) levels are referred t ...

. There are both

hormonal A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physiology and behavior. Hormones a ...

and non-hormonal treatments to prevent the negative effects of low estrogen levels and improve quality of life.

Signs and symptoms

Vasomotor

Presentations of low estrogen levels include hot flashes, which are sudden, intense feelings of heat predominantly in the upper body, causing the skin to redden as if blushing. They are believed to occur due to the narrowing of the thermonuclear zone in the

hypothalamus The hypothalamus (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrin ...

, making the body more sensitive to body temperature changes. Night disturbances are also common symptoms associated with hypoestrogenism. People may experience difficulty falling asleep, waking up several times a night, and early awakening with different variability between races and ethnic groups.

Genitourinary

Other classic symptoms include both physical and chemical changes of the

vulva In mammals, the vulva (: vulvas or vulvae) comprises mostly external, visible structures of the female sex organ, genitalia leading into the interior of the female reproductive tract. For humans, it includes the mons pubis, labia majora, lab ...

, vagina, and

lower urinary tract Lower may refer to: * ''Lower'' (album), 2025 album by Benjamin Booker *Lower (surname) *Lower Township, New Jersey *Lower Receiver (firearms) *Lower Wick Lower Wick is a small hamlet located in the county of Gloucestershire, England. It is sit ...

. Genitals go through atrophic changes such as losing elasticity, losing vaginal

rugae In anatomy, rugae (: ruga) are a series of ridges produced by folding of the wall of an organ. In general, rugae are a biological feature found in many organisms, serving purposes such as increasing surface area, flexibility, or structural sup ...

, and increasing of vaginal pH, which can lead to changes in the

vaginal flora Vaginal flora, vaginal microbiota or vaginal microbiome are the microorganisms that colonize the vagina. They were discovered by the German gynecologist Albert Döderlein in 1892 and are part of the overall human flora. The amount and type of ba ...

and increase the risk of tissue fragility and

fissure A fissure is a long, narrow crack opening along the surface of Earth. The term is derived from the Latin word , which means 'cleft' or 'crack'. Fissures emerge in Earth's crust, on ice sheets and glaciers, and on volcanoes. Ground fissure A ...

. Other genital signs include dryness or lack of

lubrication Lubrication is the process or technique of using a lubricant to reduce friction and wear and tear in a contact between two surfaces. The study of lubrication is a discipline in the field of tribology. Lubrication mechanisms such as fluid-lubr ...

, burning, irritation, discomfort or pain, as well as impaired function. Low levels of estrogen can lead to limited genital arousal and cause

dyspareunia Dyspareunia ( ) is painful sexual intercourse due to somatic or psychological causes. The term ''dyspareunia'' covers both female dyspareunia and male dyspareunia, but many discussions that use the term without further specification concern the f ...

, or painful sexual intercourse because of changes in the four layers of the vaginal wall. People with low estrogen will also experience higher urgency to urinate and

dysuria Dysuria refers to painful or uncomfortable urination. It is one of a constellation of ''irritative'' bladder symptoms (also sometimes referred to as lower urinary tract symptoms), which includes nocturia and urinary frequency. Diagnosis The cl ...

, or painful urination. Hypoestrogenism is also considered one of the major risk factors for developing uncomplicated urinary tract infection in postmenopausal women who do not take

hormone replacement therapy Hormone replacement therapy (HRT), also known as menopausal hormone therapy or postmenopausal hormone therapy, is a form of hormone therapy used to treat symptoms associated with female menopause. Effects of menopause can include symptoms such ...

Bone health

Estrogen contributes to bone health in several ways; low estrogen levels increase

bone resorption Bone resorption is resorption of bone tissue, that is, the process by which osteoclasts break down the tissue in bones and release the minerals, resulting in a transfer of calcium from bone tissue to the blood. The osteoclasts are multi-nuclea ...

via

osteoclast An osteoclast () is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and bone remodeling, remodeling of bones of the vertebrate, vertebral skeleton. The osteoclast disassembles and digests th ...

s and

osteocyte An osteocyte, an oblate-shaped type of bone cell with dendritic processes, is the most commonly found cell in mature bone. It can live as long as the organism itself. The adult human body has about 42 billion of them. Osteocytes do not divide an ...

s, cells that help with

bone remodeling 300 px, Bone tissue is removed by osteoclasts, and then new bone tissue is formed by osteoblasts. Both processes utilize cytokine ( Insulin-like_growth_factor.html" ;"title="TGF-β, Insulin-like growth factor">IGF) signalling. In osteology, bone ...

, making bones more likely to deteriorate and increase risk of fracture. The decline in estrogen levels can ultimately lead to more serious illnesses, such as

scoliosis Scoliosis (: scolioses) is a condition in which a person's Vertebral column, spine has an irregular curve in the coronal plane. The curve is usually S- or C-shaped over three dimensions. In some, the degree of curve is stable, while in others ...

or type I

, a disease that thins and weakens bones, resulting in low

bone density Bone density, or bone mineral density, is the amount of bone mineral in bone tissue. The concept is of mass of mineral per volume of bone (relating to density in the physics sense), although medicine#Clinical practice, clinically it is measured by ...

and fractures. Estrogen deficiency plays an important role in osteoporosis development for both genders, and it is more pronounced for women and at younger (menopausal) ages by five to ten years compared with men. Females are also at higher risk for

osteopenia Osteopenia, known as "low bone mass" or "low bone density", is a condition in which bone mineral density is low. Because their bones are weaker, people with osteopenia may have a higher risk of fractures, and some people may go on to develop o ...

and

Causes

A variety of conditions can lead to hypoestrogenism:

menopause Menopause, also known as the climacteric, is the time when Menstruation, menstrual periods permanently stop, marking the end of the Human reproduction, reproductive stage for the female human. It typically occurs between the ages of 45 and 5 ...

is the most common. Primary ovarian insufficiency (premature menopause) due to varying causes, such as

radiation therapy Radiation therapy or radiotherapy (RT, RTx, or XRT) is a therapy, treatment using ionizing radiation, generally provided as part of treatment of cancer, cancer therapy to either kill or control the growth of malignancy, malignant cell (biology), ...

chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...

, or a spontaneous manifestation, can also lead to low estrogen and

infertility In biology, infertility is the inability of a male and female organism to Sexual reproduction, reproduce. It is usually not the natural state of a healthy organism that has reached sexual maturity, so children who have not undergone puberty, whi ...

Hypogonadism Hypogonadism means diminished functional activity of the human gonad, gonads—the testicles or the ovary, ovaries—that may result in diminished biosynthesis, production of sex hormones. Low androgen (e.g., testosterone) levels are referred t ...

(a condition where the

gonads A gonad, sex gland, or reproductive gland is a mixed gland and sex organ that produces the gametes and sex hormones of an organism. Female reproductive cells are egg cells, and male reproductive cells are sperm. The male gonad, the testicle, ...

–

testes A testicle or testis ( testes) is the gonad in all male bilaterians, including humans, and is homologous to the ovary in females. Its primary functions are the production of sperm and the secretion of androgens, primarily testosterone. The ...

for men and

ovaries The ovary () is a gonad in the female reproductive system that produces ova; when released, an ovum travels through the fallopian tube/oviduct into the uterus. There is an ovary on the left and the right side of the body. The ovaries are endocr ...

for women – have diminished activity) can decrease estrogen. In

primary hypogonadism Hypergonadotropic hypogonadism (HH), also known as primary or peripheral/gonadal hypogonadism or primary gonadal failure, is a condition which is characterized by hypogonadism which is due to an impaired response of the gonads to the gonadotropins ...

, elevated serum

gonadotropin Gonadotropins are glycoprotein hormones secreted by gonadotropic cells of the anterior pituitary of vertebrates. They are central to the complex endocrine system that regulates normal growth, sexual development, and reproductive function. T ...

s are detected on at least two occasions several weeks apart, indicating gonadal failure. In secondary hypogonadism (where the cause is hypothalamic or

pituitary The pituitary gland or hypophysis is an endocrine gland in vertebrates. In humans, the pituitary gland is located at the base of the brain, protruding off the bottom of the hypothalamus. The pituitary gland and the hypothalamus control much of th ...

dysfunction) serum levels of gonadotropins may be low. Other causes include certain medications, gonadotropin insensitivity,

inborn errors of steroid metabolism An inborn error of steroid metabolism is an inborn error of metabolism due to defects in steroid metabolism. Types A variety of conditions of abnormal steroidogenesis exist due to genetic mutations in the steroidogenic enzymes involved in the pr ...

(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

in women who reach early menopause. Estrogen is needed to relax arteries using endothelial-derived

nitric oxide Nitric oxide (nitrogen oxide, nitrogen monooxide, or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes den ...

resulting in better

heart The heart is a muscular Organ (biology), organ found in humans and other animals. This organ pumps blood through the blood vessels. The heart and blood vessels together make the circulatory system. The pumped blood carries oxygen and nutrie ...

health by decreasing adverse

atherogenic Atherosclerosis is a pattern of the disease arteriosclerosis, characterized by development of abnormalities called lesions in walls of arteries. This is a chronic inflammatory disease involving many different cell types and is driven by eleva ...

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 Estrogen receptors (ERs) are proteins found in cell (biology), cells that function as receptor (biochemistry), receptors for the hormone estrogen (17β-estradiol). There are two main classes of ERs. The first includes the intracellular estrogen ...

function due to their embryological development. Estrogen is a

vasoactive A vasoactive substance is an endogenous agent or pharmaceutical drug that has the effect of either increasing or decreasing blood pressure and/or heart rate through its vasoactivity, that is, vascular activity (effect on blood vessels). By adjust ...

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

. This rugae aids in sexual stimulation by becoming lubricated, distended, and expanded. Genitourinary effects of low estrogen include thinning of the vaginal

epithelium Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...

, 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 The Bartholin's glands (named after Caspar Bartholin the Younger; also called Bartholin glands or greater vestibular glands) are two pea-sized compound alveolar glandsManual of Obstetrics. (3rd ed.). Elsevier. pp. 1-16. . located slightly posteri ...

, 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 ''Lactobacillus'' is a genus of gram-positive, aerotolerant anaerobes or microaerophilic, rod-shaped, non-spore-forming bacteria. Until 2020, the genus ''Lactobacillus'' comprised over 260 phylogenetically, ecologically, and metabolically div ...

'', which typically comprise more than 70% of the vaginal bacteria in women. These lactobacilli process

glycogen Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy storage in animals, fungi, and bacteria. It is the main storage form of glucose in the human body. Glycogen functions as one of three regularly used forms ...

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 The progestogen challenge test, or progesterone withdrawal test, is a test used in the field of obstetrics and gynecology to evaluate a patient who is experiencing amenorrhea. Due to readily available assays to measure serum estradiol levels, thi ...

, 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. There is no definitive testing available for determining menopause as the symptom complex is the primary indicator and because the lower levels of estradiol are harder to accurately detect after menopause. However, there can be laboratory tests done to differentiate between menopause and other diagnoses.

Functional hypothalamic amenorrhea

Functional hypothalamic amenorrhea (FHA) is diagnosed based on findings of amenorrhea lasting three months or more, low serum hormone of gonadotropins and estradiol. Since common causes of FHA include exercising too much, eating too little, or being under too much stress, diagnosis of FHA includes assessing for any changes in exercise, weight, and stress. In addition, evaluation of amenorrhea includes a history and physical examination, biochemical testing, imaging, and measuring estrogen level. Examination of menstrual problems and clinical tests to measure hormones such as serum

prolactin Prolactin (PRL), also known as lactotropin and mammotropin, is a protein best known for its role in enabling mammals to produce milk. It is influential in over 300 separate processes in various vertebrates, including humans. Prolactin is secr ...

, thyroid-stimulating hormone, and

follicle-stimulating hormone Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone. FSH is synthesized and secreted by the gonadotropic cells of the anterior pituitary gland and regulates the development, growth, puberty, pubertal maturat ...

(FSH) can help rule out other potential causes of amenorrhea. These potential conditions include

hyperprolactinemia Hyperprolactinaemia (also spelled hyperprolactinemia) is a condition characterized by abnormally high levels of prolactin in the blood. In women, normal prolactin levels average to about 13 ng/mL, while in men, they average 5 ng/mL. ...

, POI, and

polycystic ovary syndrome Polycystic ovary syndrome, or polycystic ovarian syndrome, (PCOS) is the most common endocrine disorder in women of reproductive age. The name is a misnomer, as not all women with this condition develop cysts on their ovaries. The name origin ...

Primary ovarian insufficiency

Primary ovarian insufficiency Primary ovarian insufficiency (POI), also called premature ovarian insufficiency and premature ovarian failure, is the partial or total loss of reproductive and hormonal function of the ovaries before age 40 because of follicular (egg producing ...

, also known as premature ovarian failure, can develop in women before the age of forty as a consequence of hypergonadotropic hypogonadism. POI can present as amenorrhea and has similar symptoms to menopause, but measuring FSH levels is used for diagnosis.

Treatment

Hormone replacement therapy Hormone replacement therapy (HRT), also known as menopausal hormone therapy or postmenopausal hormone therapy, is a form of hormone therapy used to treat symptoms associated with female menopause. Effects of menopause can include symptoms such ...

(HRT) can be used to treat hypoestrogenism and menopause related symptoms, and low estrogen levels in both

premenopausal Menopause, also known as the climacteric, is the time when menstrual periods permanently stop, marking the end of the reproductive stage for the female human. It typically occurs between the ages of 45 and 55, although the exact timing can ...

and postmenopausal women. Low-dose estrogen medications are approved by the U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

for treatment of menopause-related symptoms. HRT can be used with or without a

progestogen Progestogens, also sometimes written progestins, progestagens or gestagens, are a class of natural or synthetic steroid hormones that bind to and activate the progesterone receptors (PR). Progesterone is the major and most important progestoge ...

to improve symptoms such as hot flashes, sweating, trouble sleeping, vaginal dryness and discomfort. The FDA recommends HRT to be avoided in women with a history or risk of breast cancer, undiagnosed genital bleeding, untreated high blood pressure, unexplained blood clots, or liver disease. HRT for the vasomotor symptoms of hypoestrogenism include different forms of estrogen, such as conjugated equine estrogens, 17β-estradiol, transdermal estradiol, ethinyl estradiol, and the estradiol ring. In addition to HRT, there are common progestogens that are used to protect the inner layer of the uterus, the endometrium. These medications include

medroxyprogesterone acetate Medroxyprogesterone acetate (MPA), also known as depot medroxyprogesterone acetate (DMPA) in injectable form and sold under the brand name Depo-Provera among others, is a hormonal medication of the progestin type. It is used as a method of ...

progesterone Progesterone (; P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the ma ...

norethisterone acetate Norethisterone acetate (NETA), also known as norethindrone acetate and sold under the brand name Primolut-Nor among others, is a progestin medication which is used in birth control pills, menopausal hormone therapy, and for the treatment of gynec ...

, and

drospirenone Drospirenone is a progestin and antiandrogen medication which is used in birth control pills to prevent pregnancy and in menopausal hormone therapy, among other uses. It is available both alone under the brand name Slynd and in combination ...

. Non-pharmacological treatment of hot flashes includes using portable fans to lower the room temperature, wearing layered clothing, and avoiding tobacco, spicy food, alcohol and caffeine. There is a lack of evidence to support other treatments such as

acupuncture Acupuncture is a form of alternative medicine and a component of traditional Chinese medicine (TCM) in which thin needles are inserted into the body. Acupuncture is a pseudoscience; the theories and practices of TCM are not based on scientif ...

, yoga, and exercise to reduce symptoms.

In men

Estrogens are also important in male physiology. Hypoestrogenism can occur in men due to

. Very rare causes include aromatase deficiency and

estrogen insensitivity syndrome Estrogen insensitivity syndrome (EIS), or estrogen resistance, is a form of congenital estrogen deficiency or hypoestrogenism which is caused by a defective estrogen receptor (ER) – specifically, the estrogen receptor alpha (ERα) – that r ...

. Medications can also be a cause of hypoestrogenism in men. Hypoestrogenism in men can lead to

, among other symptoms. Estrogens may also be positively involved in

sexual desire Sexual desire is an emotion and motivational state characterized by an interest in sexual objects or activities, or by a drive to seek out sexual objects or to engage in sexual activities. It is an aspect of sexuality, which varies significantly ...

in men.

References

External links

{{Gonadal disorder Endocrine gonad disorders Estrogens Intersex variations