Pediatric Hypopituitarism 

Updated: Jun 06, 2018
Author: Romesh Khardori, MD, PhD, FACP; Chief Editor: Sasigarn A Bowden, MD 



Hypopituitarism is a partial or complete insufficiency of pituitary hormone secretion that may derive from pituitary or hypothalamic disease. The onset can be at any time of life. The focus of this article is childhood-onset hypopituitarism. (See the image below.)

The left photograph shows an untreated 21-month-ol The left photograph shows an untreated 21-month-old girl with congenital hypopituitarism. The right panel depicts the same child aged 29 months, following 8 months of growth hormone therapy.

Intrinsic pituitary disease, or any process that disrupts the pituitary stalk or damages the hypothalamus, may produce pituitary hormone deficiency. The clinical presentation of hypopituitarism may vary, depending on patient age and on the specific hormone deficiencies, which may occur singly or in various combinations. As a general rule, diagnosis of a single pituitary hormone deficiency requires evaluating the other hormone axes. (See Etiology, History, and Physical Examination.)

Pituitary gland development and physiology

The pituitary gland, located at the base of the brain, is composed of anterior (ie, adenohypophysis) and posterior (ie, neurohypophysis) regions. The anterior pituitary, an ectodermal structure that derives from the pharynx as the Rathke pouch, produces most of the gland’s hormones. The major biologically active hormones released into systemic circulation from the anterior pituitary include the following:

  • Growth hormone (GH)

  • Adrenocorticotropic hormone (ACTH)

  • Thyroid-stimulating hormone (TSH)

  • Luteinizing hormone (LH)

  • Follicle-stimulating hormone (FSH)

  • Prolactin (PRL)

The pathway from embryogenesis to the full differentiation of specific functional cell types within the pituitary is controlled by numerous genes that encode transcription factors. (See the diagram below.) Mutations in these genes are causes of congenital hypopituitarism and have specific pituitary hormone deficiencies associated with the involved gene. (See Etiology.)

Regulation of the development of the mammalian ant Regulation of the development of the mammalian anterior pituitary gland by transcription factors. Following, inductive signals between the developing diencephalon and the oral ectoderm, early transcription factors guide the formation of rudimentary Rathke's Pouch (rRP) and then subsequent gene regulatory pathways control the determination, proliferation, and differentiation events that establish the specialized hormone-secreting cells. AP = anterior pituitary, IP = intermediate pituitary, PP = posterior pituitary. Modified by S. Rhodes from Mullen, R.D., Colvin, S.C., Hunter, C.H., Savage, J.J., Walvoord, E.C., Bhangoo, A.P.S., Ten, T., Weigel, J., Pfäffle, R.W., and Rhodes, S.J. (2007). Roles of the LHX3 and LHX4 LIM-homeodomain factors in pituitary development. Mol. Cell. Endocrinol., 265-266: 190-195.

The anterior pituitary is primarily regulated by neuropeptide-releasing and release-inhibiting hormones produced in the hypothalamus. These regulatory hormones are transported to the anterior pituitary via the pituitary portal system circulation. The release-stimulating hormones produced by the hypothalamus include the following:

  • Growth hormone–releasing hormone (GHRH)

  • Corticotropin-releasing hormone (CRH)

  • Thyrotropin-releasing hormone (TRH)

  • Gonadotropin-releasing hormone (GnRH)

PRL secretion is distinct from that of the other anterior pituitary hormones, being inhibited by hypothalamic dopamine. In addition, antidiuretic hormone (ADH) produced in the hypothalamus acts synergistically with CRH to promote ACTH release.

A negative feedback loop occurs such that the hormones produced in the target glands feed back to inhibit the release of their respective regulatory pituitary and hypothalamic factors. For example, hypothalamic TRH stimulates TSH release, which in turn stimulates the thyroid gland, resulting in increased serum levels of thyroxine (T4) and triiodothyronine (T3). When they have reached sufficient levels, T3 and T4 suppress TRH and TSH release.

The posterior pituitary consists of neural tissue that descends from the floor of the third ventricle. In contrast to the anterior pituitary hormones, the posterior pituitary hormones (ie, ADH, oxytocin) are synthesized by cell bodies in the hypothalamus and transported along the neurohypophyseal tract of the pituitary stalk. Release of these hormones occurs in response to neurohypophyseal stimuli.


Hypopituitarism has multiple possible etiologies either from congenital or acquired mechanisms. The common endpoint is disrupted synthesis or release of 1 or more pituitary hormones, resulting in clinical manifestations of hypopituitarism.

Genetic causes of hypopituitarism are relatively rare. However, research since the late 20th century has brought considerable advances in the understanding of the various genetic causes of congenital hypopituitarism. Inheritance patterns may be autosomal recessive, autosomal dominant, or X-linked recessive. The phenotype and severity of clinical findings in congenital hypopituitarism are determined by the specific genetic mutation.[1]

Mutations in pituitary transcription factors can cause multiple pituitary hormone deficiencies (MPHD) or, less commonly, an isolated pituitary hormone deficiency. Mutations in PIT1 (POUF1)[2] and PROP1[3, 4] (ie, prophet of Pit-1) were the first mutations shown to cause MPHD. Mutations in the PIT1 gene produce a phenotype consisting of deficiencies of GH, PRL, and TSH.

PROP1 is expressed before Pit-1 and is a prerequisite for the expression of Pit-1. Inactivating mutations of PROP1 cause deficiencies of LH, FSH, GH, PRL, and TSH. Clinical phenotypes of patients with MPHD with PROP1 defects, determined by the pattern of hormone deficiency, can vary considerably even among patients with the same mutation.[5, 6]

Mutations in genes LHX3 and LHX4, which are expressed prior to Pit-1 and PROP1, have also been described as causing a phenotype of MPHD.[7] Homozygous inactivating mutations in HESX1 produce a complex phenotype with pituitary hypoplasia that resembles septo-optic dysplasia (SOD).[8] Most cases of SOD remain sporadic without a known genetic defect, and much remains to be learned about the role of HESX1 in other forms of hypopituitarism. Mutations in the GH gene or the GHRH gene lead to isolated GH deficiency (GHD). Mutations in the genes KAL and KISS1R lead to isolated gonadotropin deficiency. KAL plays a causative role in some forms of Kallmann syndrome.

Causes of hypopituitarism can be divided into categories of congenital and acquired causes. An overview of causes based on categories is summarized below.

Congenital etiologies

Congenital causes of hypopituitarism include the following:

  • Perinatal insults (eg, traumatic delivery, birth asphyxia)

  • Interrupted pituitary stalk[9]

  • Absent or ectopic neurohypophysis

  • Pallister-Hall syndrome (Hypothalamic hamartoma and polydactyly)

Genetic disorders causing hypopituitarism include the following:

  • Isolated GH deficiency types IA, IB, II, III

  • MPHD [Multiple Pituitary Hormone Deficiency] (eg, from PIT1 and PROP1 mutations)

  • Septo-optic dysplasia

  • Isolated gonadotropin deficiency (eg, from KAL and KISS1R mutations)

Developmental central nervous system (CNS) defects that cause hypopituitarism include the following:

  • Anencephaly

  • Holoprosencephaly [brain fails to divide properly into right and left hemispheres)

  • Pituitary aplasia or hypoplasia

Acquired etiologies

Cranial irradiation and hemochromatosis can lead to hypopituitarism. Delayed presentation of pituitary hormone deficiencies from radiation-induced damage[10] resulting from therapy for CNS and non-CNS tumors has received increased recognition. (See the chart below.) There is also now a recognition of immediate and delayed endocrine sequelae in survivors of traumatic brain injury.[11, 12]  A recent review[28] addresses endocrine dysfunction following pediatric traumatic brain injury. In the era of use of biologics for cancer treatment, drug induced hypophysitis and hypopituitarism must be considered as well.[29]

Infiltrative disorders that can cause hypopituitarism include the following:

  • Histiocytosis X

  • Tuberculosis

  • Sarcoidosis

  • Lymphocytic hypophysitis

Tumors (eg, sellar, suprasellar, pineal) that can result in hypopituitarism include the following:

  • Craniopharyngioma[13]

  • Germinoma[14]

  • Glioma/astrocytoma

  • Pituitary adenoma (rare prior to adulthood)


MPHD is rare in childhood, with a possible incidence of fewer than 3 cases per million people per year. The most common pituitary hormone deficiency, GHD, is much more frequent; a US study reported a prevalence of 1 case in 3480 children.[15] A 2001 population study in adults in Spain estimated the annual incidence of hypopituitarism at 4.2 cases per 100,000 population.[16]

Because hypopituitarism has congenital and acquired forms, the disease can occur in neonates, infants, children, adolescents, and adults.


With appropriate treatment, the overall prognosis in hypopituitarism is very good. Sequelae from episodes of severe hypoglycemia, hypernatremia, or adrenal crises are among potential complications. Long-term complications include short stature, osteoporosis, increased cardiovascular morbidity/mortality, and infertility. Previous findings of increased cardiovascular morbidity and decreased life expectancy in adults with hypopituitarism were thought to be largely secondary to untreated GHD.


Morbidity and mortality statistics generally cannot be viewed in isolation but must instead be related to the underlying cause of hypopituitarism. For example, morbidity and mortality are minimal in the context of idiopathic GHD compared with hypopituitarism caused by craniopharyngioma.

Recognition of pituitary insufficiency and appropriate hormone replacement (including stress doses of hydrocortisone, when indicated) are essential for the avoidance of unnecessary morbidity and mortality. Clinical manifestations of isolated or multiple deficiencies in pituitary hormones (anterior and/or posterior) can result in significant sequelae that include any of the following:

  • Hypoglycemia - Can cause convulsions; persistent, severe hypoglycemia can cause permanent CNS injury.

  • Adrenal crisis - Can occur during periods of significant stress, from ACTH or CRH deficiency; symptoms include profound hypotension, severe shock, and death.

  • Short stature - Can have significant psychosocial consequences.

  • Hypogonadism and impaired fertility - From gonadotropin deficiency

  • Osteoporosis - Results in increased fracture risk as an adult

GHD is believed to be an important contributing factor to morbidity and mortality associated with hypopituitarism. In a 2008 study, childhood onset GHD was associated with an increased hazard ratio for morbidity of greater than 3.0 for males and females.[17] Causes of morbidity and mortality are multifactorial and relate to the specific cause of hypopituitarism, as well as to the degree of pituitary hormone deficiency.

Patient Education

Teaching patients when and how to administer appropriate stress doses (oral and parenteral) of hydrocortisone is essential. When treatment includes recombinant human growth hormone (rhGH) therapy, instruct parents and patients to recognize and report adverse effects.

Express the importance of wearing a medical identification bracelet or necklace. Genetic counseling with parents and patients about the mode of transmission of hypopituitarism is important for cases involving heritable forms of the disease.




The clinical presentation of hypopituitarism, which widely varies, depends on the patient's age, the etiology, and the specific hormone deficiencies, which may occur as isolated deficiencies or in various combinations of MPHD. Presenting signs and symptoms may develop insidiously and can be nonspecific, requiring a high index of suspicion.


Most neonates with hypopituitarism have normal or even high birth weights and lengths and no history of intrauterine growth retardation. However, they often have histories of breech presentation (particularly neonates with MPHD), although the explanation for this is unclear. Microgenitalia, mainly in males, may result from a gonadotropin deficiency or from GH deficiency.

The hypoglycemia risk is higher in neonates with hypopituitarism, with various manifesting symptoms, such as lethargy, jitteriness, pallor, cyanosis, apnea, or convulsions. Jaundice may be secondary to indirect hyperbilirubinemia (as occurs in TSH axis deficiency) or to direct hyperbilirubinemia (as occurs in GH or ACTH axis deficiencies).

Neonates with hypopituitarism may have undergone several evaluations to exclude sepsis or for unexplained apnea, hypotension, or temperature instability. Consider hypopituitarism as a possible diagnosis when these conditions occur in a full-term infant.

Electrolyte disturbances can also occur in neonates with hypopituitarism. Hyponatremia unassociated with hypovolemia and unresponsive to fluid restriction can develop. In contrast to the hyponatremia that occurs with the salt-losing crisis of 21-hydroxylase deficiency, serum potassium levels are typically low or within the reference range. The hyponatremia resolves with physiologic corticosteroid replacement.[18] Hypernatremia secondary to excess free-water loss associated with uncontrolled diabetes insipidus may also occur.

Depending on the etiology of the hypopituitarism, associated findings in the neonate, infant, or child may include developmental delay, various visual and neurologic symptoms, seizure disorder, and a number of congenital malformation syndromes.

Older infants and children

Common presenting features include growth failure, disorders of pubertal development, and diabetes insipidus. Growth failure may be the most common presenting symptom in this age group, possibly with an associated delay in tooth development. Hypoglycemia, although less frequent, can also be a presenting sign of hypopituitarism in older infants and children. Patients with acquired or milder forms of gonadotropin deficiency who do not present with microgenitalia in infancy may present later with absent or delayed puberty.

Central diabetes insipidus secondary to ADH deficiency can be difficult to recognize in infancy, because patients often present with nonspecific signs (eg, irritability, unexplained fever). Symptoms of polyuria and polydipsia are more readily obvious in older children.

Patients with hypothyroidism secondary to a TSH axis deficiency present with signs and symptoms identical to those of primary hypothyroidism, although typically less severe. These include fatigue, cold intolerance, constipation, dry skin, slow growth, and weight gain.

Depending on the etiology of the hypopituitarism, associated findings in the neonate, infant, or child may include developmental delay, various visual and neurologic symptoms, seizure disorder, and a number of congenital malformation syndromes. Optic nerve hypoplasia has been associated with a spectrum of endocrine abnormalities, from isolated GHD to MPHD. Patients with acquired hypopituitarism, caused by a suprasellar tumor, often present with headaches, visual disturbances, and other neurologic symptoms.

Anencephaly is associated with variable pituitary hypoplasia and complete absence of the hypothalamus. Various forms of holoprosencephaly particular associated with HESX1 mutations may be associated with hypopituitarism.

Physical Examination


Birth weights and lengths are typically within the reference range in neonates with hypopituitarism. Important physical signs in the neonate that may suggest a diagnosis of hypopituitarism include microgenitalia, jaundice, and physical evidence of possible hypoglycemia (ie, jitteriness, pallor).[19]

Microgenitalia includes micropenis (which has a well-documented association with hypopituitarism) and an underdeveloped clitoris. Micropenis is defined as stretched penile length less than 2.5 cm (reference range mean length is 4 cm). Data on normal clitoral size, including that for different gestational ages, are also available.[20] Cryptorchidism is often associated with micropenis.

Optic nerve hypoplasia is associated with hypopituitarism; the presence of small, pale optic disks or nystagmus should prompt consideration of hypopituitarism.[21, 22]

Older infants and children

Growth failure (see the image below) is the most important sign to recognize in hypopituitarism. Growth failure may often exist for a considerable period of time before it is recognized. In addition to short stature and abnormal growth rate, the affected child may show evidence of delayed skeletal maturation (eg, delayed dental development).

The left photograph shows an untreated 21-month-ol The left photograph shows an untreated 21-month-old girl with congenital hypopituitarism. The right panel depicts the same child aged 29 months, following 8 months of growth hormone therapy.

During the physical examination, pay particular attention to pubertal development, because patients with hypopituitarism may present with microgenitalia in infancy or with delayed or absent puberty. Anosmia, particularly in a patient with delayed or absent puberty, should prompt consideration of Kallmann syndrome (KS).

Weight gain typically is out of proportion to growth, resulting in relative obesity. This obesity is truncal in distribution; skull and head circumference growth are typically preserved, producing the impression of a large head. Craniofacial features of pituitary GHD include craniofacial disproportion (ie, normal head circumference, small facies, prominent forehead, frontal bossing). The presence of a central incisor is an important, finding because it may represent hypopituitarism in a midline CNS abnormality.

Visual and neurologic abnormalities may represent important features associated with hypopituitarism. When not recognized in infancy, optic nerve hypoplasia may be noted in childhood as decreased visual acuity. Signs that may indicate the potential presence of a suprasellar mass include decreased visual acuity, visual field defects, papilledema, and/or optic atrophy.





Approach Considerations

Laboratory tests are essential in the diagnosis and assessment of patients with hypopituitarism. However, any patient with hypopituitarism must also have a magnetic resonance imaging (MRI) examination to exclude a brain tumor. A brain MRI with specific cuts of the pituitary is the preferred imaging study for hypopituitarism.[23] This may be obtained pre–gadolinium contrast and post–gadolinium contrast, which can be helpful in the delineation of the posterior pituitary and some pituitary tumors.

Laboratory Studies

Screening for GHD using insulinlike growth factor-I (IGF-I) and insulinlike growth factor–binding protein 3 (IGFBP-3) may be useful,[24] except in cases of brain tumors.[25] Random measurement of GH levels has no diagnostic value except during early infancy, when GH levels are usually tonically elevated.

If abnormal growth patterns are seen, and GHD is strongly suspected, further provocative testing of GH secretion is typically performed under the supervision of a pediatric endocrinologist. Insulin-induced hypoglycemia is the most reliable provocative test for GHD and has the added advantage of accurately assessing the CRH-ACTH-cortisol axis. However, this test also has the greatest potential for harm, making its use limited in many pediatric endocrine practices. Currently, Glucagon Stimulation test is recommended for estimation of growth hormone secretion.

Alternative GH secretagogues used successfully in combination as 2 serial tests include arginine, levodopa, GHRH, propranolol with glucagon, exercise, clonidine, and epinephrine. In prepubertal children, consideration should be given to "priming" with sex steroids prior to testing.

Measurement of morning serum cortisol levels can help to exclude a CRH-ACTH-cortisol axis deficiency; a level of 20 mcg/dL virtually excludes this diagnosis.

Insulin-induced hypoglycemia probably is the criterion standard test but has limitations secondary to its inherent risks. On the other hand, ACTH stimulation testing is sensitive, reproducible, and extremely safe. Even though it directly examines the state of the adrenal cortices, indirectly it provides information about the hypothalamic-pituitary unit, because the cortisol response to exogenous ACTH is blunted in long-standing (>10 d) hypopituitarism.

Tests for adrenal insufficiency using Metyrapone or CRH are less-used laboratory examinations in pediatric patients. In patients with acute hypoglycemia, a critical sample documenting low serum glucose, while simultaneously measuring GH and cortisol levels, can be diagnostic. To assess central hypothyroidism (ie, TSH or TRH deficiency), low free thyroxine (FT4) levels assayed by dialysis and reference range or low serum TSH levels are diagnostic.[26]

Laboratory approaches to assess the pituitary-gonadal axis vary based on patient age. Young infants spontaneously secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in amounts that can be detected by radioimmunoassay; they also produce substantial amounts of testosterone and estradiol (Mini Puberty). At this age, random measurements of estradiol or testosterone levels and of LH and FSH levels are adequate to assess the gonadal axis.

From later infancy until about age 4 years, spontaneous secretion of LH and FSH is reduced, but stimulated responses to GnRH are retained, making GnRH testing an option. No method reliably assesses the axis in preadolescent children older than age 4 years. Testing is typically deferred until puberty, when diagnostic findings show low random LH and FSH levels in conjunction with low sex steroid levels (eg, testosterone, estradiol).

Elevated serum sodium and serum osmolality levels, when combined with low or low-normal urine osmolality, suggest diabetes insipidus. A low serum ADH level in this context can be diagnostic for central diabetes insipidus (ie, pituitary vasopressin deficiency). A water deprivation test is definitive; this test is performed under the supervision of a pediatric endocrinologist. In patients with diabetes insipidus, serum sodium and serum osmolality levels rise during water deprivation, while urine fails to concentrate properly. A normal response to administered vasopressin differentiates central diabetes insipidus from nephrogenic diabetes insipidus.



Approach Considerations

Treatment for hypopituitarism primarily involves appropriate hormone replacement.[27] The presence of 1 or more hormone deficiencies determines medication choice. Conduct appropriate stress dosing of corticosteroid replacement. Surgical intervention can be employed in tumor-associated hypopituitarism, with the tumor location and type dictating the choice of surgical procedure.

Diet and activity are typically unrestricted in patients with hypopituitarism, but special situations do apply that can impact these areas, depending on the underlying cause of hypopituitarism.


Consultations are dependent on the etiology of hypopituitarism. Some of the consultants that may be involved in the care of patients with hypopituitarism come from the following specialties:

  • Ophthalmology - Optic nerve hypoplasia, septo-optic dysplasia, pituitary tumors

  • Neurology - Septo-optic dysplasia, holoprosencephaly, traumatic brain injury, pituitary tumors or other CNS tumors

  • Genetics - Congenital hypopituitarism, septo-optic dysplasia, holoprosencephaly

  • Oncology - CNS tumors (including pituitary tumors), other malignancies

  • Rehabilitation medicine

  • Psychology services for neurodevelopmental and educational monitoring

Long-Term Monitoring

Routinely monitor growth and development at 3-month intervals in patients with hypopituitarism. If a patient is receiving recombinant human growth hormone (rhGH) therapy, monitor for adverse effects and monitor insulinlike growth factor (IGF)-I and insulinlike growth factor binding protein-3 (IGFBP3) levels at least annually. Also, consider monitoring for impaired glucose tolerance with a fasting morning blood sugar or hemoglobin A1c (HgbA1c), particularly in the patient with risk factors for diabetes mellitus (eg, family history, obesity).

Monitor thyroid functions routinely in hypopituitarism (FT4) or as part of scheduled monitoring in isolated GHD, when appropriate. Consider repeat low-dose ACTH stimulation testing in high-risk patients or if clinical symptoms of cortisol deficiency are apparent.

Home blood glucose monitoring to screen for hypoglycemia in very young patients and/or patients with central adrenal insufficiency should be strongly considered. In those patients with hypopituitarism that includes adrenal insufficiency, a medical alert bracelet should be worn, alerting first-responders of the patient’s need for stress hydrocortisone therapy.


Special considerations may apply in dietary management for children with hypopituitarism. Children with diabetes insipidus and hypopituitarism may require close monitoring of water and fluid intake to prevent excessive fluctuations in blood sodium and osmolality.

Children with hypothalamic damage in association with their hypopituitarism may be predisposed to hypothalamic obesity, with risk for rapid weight gain with morbid obesity. This subpopulation of children with hypopituitarism require close monitoring of their daily food intake.



Medication Summary

Agents used to treat hypopituitarism simply replace the deficient hormone or hormones. When appropriately administered, dosing is determined in a physiologic manner, and adverse effects are rare. Careful titration is critical. Consistent and accurate compliance with appropriately prescribed regimens is mandatory to avoid hormone deficiency or excess.

Endocrine hormones

Class Summary

These hormones are designed to replace absent hormones in patients with a pituitary deficiency.

Somatropin (Genotropin, Humatrope, Norditropin, Nutropin, Omnitrope, Saizen, Tev-Tropin)

Somatropin is an rhGH used to treat growth failure and metabolic abnormalities that accompany GHD. It is a purified polypeptide hormone of recombinant deoxyribonucleic acid (DNA) origin. The amino acid sequence of somatropin is identical to that of pituitary-derived human GH. The growth response of infants and children with severe GHD secondary to congenital hypopituitarism often is remarkable.

Levothyroxine (Synthroid, Levoxyl, Tirosint, Unithroid)

In active form, levothyroxine influences the growth and maturation of tissues. Sufficient thyroid hormone is mandatory for normal growth, metabolism, and neurologic development. For central hypothyroidism, the goal is normal FT4.

Hydrocortisone (Cortef, Solu-Cortef, A-Hydrocort)

Hydrocortisone is used for cortisol replacement therapy; it has mineralocorticoid activity and glucocorticoid effects.

Vasopressin (Pitressin)

Vasopressin is used for ADH replacement therapy mainly in the intensive care unit (ICU) or inpatient setting. It may be given as a continuous intravenous (IV) drip or as intermittent injections. The dose widely varies and is titrated depending on serum and/or urine sodium osmolality, fluid balance, and urine output.

Desmopressin (DDAVP, Stimate)

This agent increases the cellular permeability of collecting ducts, resulting in the reabsorption of water by the kidneys; it is used for ADH replacement.


Class Summary

These hormones are designed to replace testosterone absent secondary to gonadotropin deficiency.

Testosterone (Delatestryl, AndroGel, Testim)

Testosterone is an anabolic steroid that promotes and maintains secondary sex characteristics in androgen-deficient males. Dosing routes include intramuscular and transdermal. Oral forms of testosterone are very rarely used in the United States.

Estrogen Derivative

Class Summary

These hormones are designed to replace estrogen absent secondary to gonadotropin deficiency.

Estradiol (Alora, Climara, Estrace, Estraderm)

Estradiol restores estrogen levels in girls with hypogonadotropism to concentrations that induce negative feedback at gonadotrophic regulatory centers, which in turn reduces the release of gonadotropins from the pituitary. Multiple studies have shown that estradiol will prevent bone loss at the spine and hip when started within 10 years of menopause.

Estradiol is used for hormone replacement and the induction of puberty. It acts by regulating the transcription of a limited number of genes. Estrogens diffuse through cell membranes, distribute themselves throughout the cell, and bind to and activate the nuclear estrogen receptor, a DNA-binding protein found in estrogen-responsive tissues. The activated estrogen receptor binds to specific DNA sequences or hormone-response elements, which enhances transcription of adjacent genes and, in turn, leads to the observed effects.