Hypoestrogenism

Last updated

Hypoestrogenism
Other namesEstrogen deficiency
Specialty Gynecology

Hypoestrogenism, or estrogen deficiency, refers to a lower than normal level of estrogen. 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, [1] and has been linked to diseases like urinary tract infections [2] and osteoporosis.

Contents

In women, low levels of estrogen may cause symptoms such as hot flashes, sleeping disturbances, decreased bone health, [3] and changes in the genitourinary system. Hypoestrogenism is most commonly found in women who are postmenopausal, have primary ovarian insufficiency (POI), or are presenting with amenorrhea (absence of menstrual periods). Hypoestrogenism includes primarily genitourinary effects, including thinning of the vaginal tissue layers and an increase in vaginal pH. With normal levels of estrogen, the environment of the vagina is protected against inflammation, infections, and sexually transmitted infections. [4] Hypoestrogenism can also occur in men, for instance due to hypogonadism.

There are both hormonal 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, making the body more sensitive to body temperature changes. [5] 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. [6]

Genitourinary

Other classic symptoms include both physical and chemical changes of the vulva, vagina, and lower urinary tract. [7] Genitals go through atrophic changes such as losing elasticity, losing vaginal rugae, and increasing of vaginal pH, [8] which can lead to changes in the vaginal flora and increase the risk of tissue fragility and fissure. Other genital signs include dryness or lack of lubrication, burning, irritation, discomfort or pain, as well as impaired function. [9] Low levels of estrogen can lead to limited genital arousal and cause dyspareunia, or painful sexual intercourse because of changes in the four layers of the vaginal wall. [10] People with low estrogen will also experience higher urgency to urinate and dysuria, or painful urination.[ failed verification ] 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. [11]

Bone health

Estrogen contributes to bone health in several ways; [12] low estrogen levels increase bone resorption via osteoclasts and osteocytes, cells that help with bone remodeling, [13] 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 [14] or type I osteoporosis, a disease that thins and weakens bones, resulting in low bone density and fractures. [15] [16] 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 and osteoporosis. [16]

Causes

A variety of conditions can lead to hypoestrogenism: menopause is the most common. [5] 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. [17]

Hypogonadism (a condition where the gonads – testes for men and ovaries for women – have diminished activity) can decrease estrogen. [18] In primary hypogonadism, elevated serum gonadotropins are detected on at least two occasions several weeks apart, indicating gonadal failure. [18] In secondary hypogonadism (where the cause is hypothalamic or pituitary dysfunction) serum levels of gonadotropins may be low. [19]

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.[ medical citation needed ]

Risks

Low endogenous estrogen levels can elevate the risk of cardiovascular disease in women who reach early menopause. [1] Estrogen is needed to relax arteries using endothelial-derived nitric oxide resulting in better heart health by decreasing adverse atherogenic effects. [20] Women with POI may have an increased risk of cardiovascular disease due to low estrogen production. [21]

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. [22]

Genitourinary effects of low estrogen include thinning of the vaginal epithelium, loss of vaginal barrier function,[ clarification needed ] 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. [4]

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. [23]

Diagnosis

Hypoestrogenism is typically found in menopause and aids in diagnosis of other conditions such as POI and functional amenorrhea. [17] [24] Estrogen levels can be tested through several laboratory tests: vaginal maturation index,[ clarification needed ] progestogen challenge test, and vaginal swabs for small parabasal cells. [19]

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 [5] and because the lower levels of estradiol are harder to accurately detect after menopause. [25] However, there can be laboratory tests done to differentiate between menopause and other diagnoses.[ citation needed ]

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. [26] 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, thyroid-stimulating hormone, and follicle-stimulating hormone (FSH) can help rule out other potential causes of amenorrhea. These potential conditions include hyperprolactinemia, POI, and polycystic ovary syndrome. [27]

Primary ovarian insufficiency

Primary ovarian insufficiency, also known as premature ovarian failure, can develop in women before the age of forty as a consequence of hypergonadotropic hypogonadism. [19] POI can present as amenorrhea and has similar symptoms to menopause, but measuring FSH levels is used for diagnosis. [21]

Treatment

Hormone replacement therapy (HRT) can be used to treat hypoestrogenism and menopause related symptoms, and low estrogen levels in both premenopausal and postmenopausal women. Low-dose estrogen medications are approved by the U.S. Food and Drug Administration for treatment of menopause-related symptoms. HRT can be used with or without a progestogen to improve symptoms such as hot flashes, sweating, trouble sleeping, vaginal dryness and discomfort. [28] 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. [28]

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. [28] 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, progesterone, norethisterone acetate, and drospirenone. [28]

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, yoga, and exercise to reduce symptoms. [29]

In men

Estrogens are also important in male physiology. [30] [31] [32] Hypoestrogenism can occur in men due to hypogonadism. [33] Very rare causes include aromatase deficiency and estrogen insensitivity syndrome. [30] [31] [32] Medications can also be a cause of hypoestrogenism in men. [34] [35] Hypoestrogenism in men can lead to osteoporosis, among other symptoms. [30] [31] [32] Estrogens may also be positively involved in sexual desire in men. [33] [36]

See also

Related Research Articles

<span class="mw-page-title-main">Menopause</span> Time when menstrual periods stop permanently

Menopause, also known as the climacteric, is the time when menstrual periods permanently cease, marking the end of reproduction. It typically occurs between the ages of 45 and 55, although the exact timing can vary. Menopause is usually a natural change. It can occur earlier in those who smoke tobacco. Other causes include surgery that removes both ovaries or some types of chemotherapy. At the physiological level, menopause happens because of a decrease in the ovaries' production of the hormones estrogen and progesterone. While typically not needed, a diagnosis of menopause can be confirmed by measuring hormone levels in the blood or urine. Menopause is the opposite of menarche, the time when a girl's periods start.

<span class="mw-page-title-main">Estradiol</span> Chemical compound

Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous and menstrual female reproductive cycles. Estradiol is responsible for the development of female secondary sexual characteristics such as the breasts, widening of the hips and a female-associated pattern of fat distribution. It is also important in the development and maintenance of female reproductive tissues such as the mammary glands, uterus and vagina during puberty, adulthood and pregnancy. It also has important effects in many other tissues including bone, fat, skin, liver, and the brain.

Hypogonadism means diminished functional activity of the gonads—the testes or the ovaries—that may result in diminished production of sex hormones. Low androgen levels are referred to as hypoandrogenism and low estrogen as hypoestrogenism. These are responsible for the observed signs and symptoms in both males and females.

<span class="mw-page-title-main">Estradiol acetate</span> Chemical compound

Estradiol acetate (EA), sold under the brand names Femtrace, Femring, and Menoring, is an estrogen medication which is used in hormone therapy for the treatment of menopausal symptoms in women. It is taken by mouth once daily or given as a vaginal ring once every three months.

<span class="mw-page-title-main">Estrogen patch</span> Transdermal delivery system for estrogens

An estrogen patch, or oestrogen patch, is a transdermal delivery system for estrogens such as estradiol and ethinylestradiol which can be used in menopausal hormone therapy, feminizing hormone therapy for transgender women, hormonal birth control, and other uses. Transdermal preparations of estrogen are metabolized differently than oral preparations. Transdermal estrogens avoid the first pass through the liver and thus potentially reduce the risk of blood clotting and stroke.

Primary ovarian insufficiency (POI) is the partial or total loss of reproductive and hormonal function of the ovaries before age 40 because of follicular dysfunction or early loss of eggs. POI can be seen as part of a continuum of changes leading to menopause that differ from age-appropriate menopause in the age of onset, degree of symptoms, and sporadic return to normal ovarian function. POI affects approximately 1 in 10,000 women under age 20, 1 in 1,000 women under age 30, and 1 in 100 of those under age 40. A medical triad for the diagnosis is amenorrhea, hypergonadotropism, and hypoestrogenism.

<span class="mw-page-title-main">Relative energy deficiency in sport</span> Syndrome of disordered eating, oligomenorrhoea and osteopenia

Relative energy deficiency in sport (RED-S) is a syndrome in which disordered eating, amenorrhoea/oligomenorrhoea, and decreased bone mineral density are present. It is caused by eating too little food to support the amount of energy being expended by an athlete, often at the urging of a coach or other authority figure who believes that athletes are more likely to win competitions when they have an extremely lean body type. RED-S is a serious illness with lifelong health consequences and can potentially be fatal.

Functional hypothalamic amenorrhea (FHA) is a form of amenorrhea and chronic anovulation and is one of the most common types of secondary amenorrhea. It is classified as hypogonadotropic hypogonadism. It was previously known as "juvenile hypothalamosis syndrome," prior to the discovery that sexually mature females are equally affected. FHA has multiple risk factors, with links to stress-related, weight-related, and exercise-related factors. FHA is caused by stress-induced suppression of the hypothalamic-pituitary-ovarian (HPO) axis, which results in inhibition of gonadotropin-releasing hormone (GnRH) secretion, and gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Severe and potentially prolonged hypoestrogenism is perhaps the most dangerous hormonal pathology associated with the disease, because consequences of this disturbance can influence bone health, cardiovascular health, mental health, and metabolic functioning in both the short and long-term. Because many of the symptoms overlap with those of organic hypothalamic, pituitary, or gonadal disease and therefore must be ruled out, FHA is a diagnosis of exclusion; "functional" is used to indicate a behavioral cause, in which no anatomical or organic disease is identified, and is reversible with correction of the underlying cause. Diagnostic workup includes a detailed history and physical, laboratory studies, such as a pregnancy test, and serum levels of FSH and LH, prolactin, and thyroid-stimulating hormone (TSH), and imaging. Additional tests may be indicated in order to distinguish FHA from organic hypothalamic or pituitary disorders. Patients present with a broad range of symptoms related to severe hypoestrogenism as well as hypercortisolemia, low serum insulin levels, low serum insulin-like growth factor 1 (IGF-1), and low total triiodothyronine (T3). Treatment is primarily managing the primary cause of the FHA with behavioral modifications. While hormonal-based therapies are potential treatment to restore menses, weight gain and behavioral modifications can have an even more potent impact on reversing neuroendocrine abnormalities, preventing further bone loss, and re-establishing menses, making this the recommended line of treatment. If this fails to work, secondary treatment is aimed at treating the effects of hypoestrogenism, hypercortisolism, and hypothyroidism.

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. These symptoms can include hot flashes, vaginal atrophy, accelerated skin aging, vaginal dryness, decreased muscle mass, sexual dysfunction, and bone loss or osteoporosis. They are in large part related to the diminished levels of sex hormones that occur during menopause.

<span class="mw-page-title-main">Aromatase deficiency</span> Medical condition

Aromatase deficiency is a rare condition characterized by extremely low levels or complete absence of the enzyme aromatase activity in the body. It is an autosomal recessive disease resulting from various mutations of gene CPY19 (P450arom) which can lead to ambiguous genitalia and delayed puberty in females, continued linear growth into adulthood and osteoporosis in males and virilization in pregnant mothers. As of 2020, fewer than 15 cases have been identified in genetically male individuals and at least 30 cases in genetically female individuals.

Vaginal estrogen is a form of estrogen that is delivered by intravaginal administration. Vaginally administered estrogens are thereby exerting their effects mainly in the nearby tissue, with more limited systemic effects compared to orally administered estrogens. It will not protect against osteoporosis. With perhaps the exception of the Femring, it also will not alleviate the hot flashes and hormonal imbalance caused by menopause.

Follicle-stimulating hormone (FSH) insensitivity, or ovarian insensitivity to FSH in females, also referable to as ovarian follicle hypoplasia or granulosa cell hypoplasia in females, is a rare autosomal recessive genetic and endocrine syndrome affecting both females and males, with the former presenting with much greater severity of symptomatology. It is characterized by a resistance or complete insensitivity to the effects of follicle-stimulating hormone (FSH), a gonadotropin which is normally responsible for the stimulation of estrogen production by the ovaries in females and maintenance of fertility in both sexes. The condition manifests itself as hypergonadotropic hypogonadism, reduced or absent puberty, amenorrhea, and infertility in females, whereas males present merely with varying degrees of infertility and associated symptoms.

Androgen deficiency is a medical condition characterized by insufficient androgenic activity in the body. Androgenic activity is mediated by androgens, and is dependent on various factors including androgen receptor abundance, sensitivity and function.

<span class="mw-page-title-main">Atrophic vaginitis</span> Medical condition

Atrophic vaginitis is inflammation of the vagina as a result of tissue thinning due to not enough estrogen. Symptoms may include pain with sex, vaginal itchiness or dryness, and an urge to urinate or burning with urination. It generally does not resolve without ongoing treatment. Complications may include urinary tract infections.

<span class="mw-page-title-main">Conjugated estrogens</span> Estrogen medication

Conjugated estrogens (CEs), or conjugated equine estrogens (CEEs), sold under the brand name Premarin among others, is an estrogen medication which is used in menopausal hormone therapy and for various other indications. It is a mixture of the sodium salts of estrogen conjugates found in horses, such as estrone sulfate and equilin sulfate. CEEs are available in the form of both natural preparations manufactured from the urine of pregnant mares and fully synthetic replications of the natural preparations. They are formulated both alone and in combination with progestins such as medroxyprogesterone acetate. CEEs are usually taken by mouth, but can also be given by application to the skin or vagina as a cream or by injection into a blood vessel or muscle.

<span class="mw-page-title-main">Estradiol (medication)</span> Steroidal hormone medication

Estradiol (E2) is a medication and naturally occurring steroid hormone. It is an estrogen and is used mainly in menopausal hormone therapy and to treat low sex hormone levels in women. It is also used in hormonal birth control for women, in hormone therapy for transgender women, and in the treatment of hormone-sensitive cancers like prostate cancer in men and breast cancer in women, among other uses. Estradiol can be taken by mouth, held and dissolved under the tongue, as a gel or patch that is applied to the skin, in through the vagina, by injection into muscle or fat, or through the use of an implant that is placed into fat, among other routes.

<span class="mw-page-title-main">Estrogen (medication)</span> Type of medication

An estrogen (E) is a type of medication which is used most commonly in hormonal birth control and menopausal hormone therapy, and as part of feminizing hormone therapy for transgender women. They can also be used in the treatment of hormone-sensitive cancers like breast cancer and prostate cancer and for various other indications. Estrogens are used alone or in combination with progestogens. They are available in a wide variety of formulations and for use by many different routes of administration. Examples of estrogens include bioidentical estradiol, natural conjugated estrogens, synthetic steroidal estrogens like ethinylestradiol, and synthetic nonsteroidal estrogens like diethylstilbestrol. Estrogens are one of three types of sex hormone agonists, the others being androgens/anabolic steroids like testosterone and progestogens like progesterone.

<span class="mw-page-title-main">Estriol (medication)</span> Chemical compound

Estriol (E3), sold under the brand name Ovestin among others, is an estrogen medication and naturally occurring steroid hormone which is used in menopausal hormone therapy. It is also used in veterinary medicine as Incurin to treat urinary incontinence due to estrogen deficiency in dogs. The medication is taken by mouth in the form of tablets, as a cream that is applied to the skin, as a cream or pessary that is applied in the vagina, and by injection into muscle.

<span class="mw-page-title-main">Estrone (medication)</span> Estrogen medication

Estrone (E1), sold under the brand names Estragyn, Kestrin, and Theelin among many others, is an estrogen medication and naturally occurring steroid hormone which has been used in menopausal hormone therapy and for other indications. It has been provided as an aqueous suspension or oil solution given by injection into muscle and as a vaginal cream applied inside of the vagina. It can also be taken by mouth as estradiol/estrone/estriol and in the form of prodrugs like estropipate and conjugated estrogens.

Opioid-induced endocrinopathy (OIE) is a complication of chronic opioid treatment. It is a common name for all hypothalamo-pituitary axis disorders, which can be observed mostly after long term use of opioids, both as a treatment and as a substance of abuse.

References

  1. 1 2 Atsma F, Bartelink ML, Grobbee DE, van der Schouw YT (2006). "Postmenopausal status and early menopause as independent risk factors for cardiovascular disease: a meta-analysis". Menopause. 13 (2): 265–79. doi:10.1097/01.gme.0000218683.97338.ea. PMID   16645540. S2CID   46530925.
  2. ↑ Perrotta C, Aznar M, Mejia R, Albert X, Ng CW (April 2008). "Oestrogens for preventing recurrent urinary tract infection in postmenopausal women". Cochrane Database Syst Rev (2): CD005131. doi:10.1002/14651858.CD005131.pub2. PMID   18425910.
  3. ↑ Prior JC (August 2018). "Progesterone for the prevention and treatment of osteoporosis in women". Climacteric. 21 (4): 366–374. doi: 10.1080/13697137.2018.1467400 . PMID   29962257. S2CID   49649035.
  4. 1 2 Naumova I, Castelo-Branco C (2018). "Current treatment options for postmenopausal vaginal atrophy". International Journal of Women's Health. 10: 387–395. doi: 10.2147/IJWH.S158913 . PMC   6074805 . PMID   30104904.
  5. 1 2 3 Warren MP, Shu AR, Dominguez JE (2000), Feingold KR, Anawalt B, Boyce A, Chrousos G (eds.), "Menopause and Hormone Replacement", Endotext, South Dartmouth (MA): MDText.com, Inc., PMID   25905278
  6. ↑ Kravitz HM, Zhao X, Bromberger JT, Gold EB, Hall MH, Matthews KA, Sowers MR (July 2008). "Sleep disturbance during the menopausal transition in a multi-ethnic community sample of women". Sleep. 31 (7): 979–90. PMC   2491500 . PMID   18652093.
  7. ↑ Portman DJ, Gass ML (October 2014). "Genitourinary syndrome of menopause: new terminology for vulvovaginal atrophy from the International Society for the Study of Women's Sexual Health and the North American Menopause Society". Menopause. 21 (10): 1063–8. doi:10.1097/GME.0000000000000329. PMID   25160739. S2CID   21886335.
  8. ↑ Sartori MG, Feldner PC, Jarmy-Di Bella ZI, Aquino Castro R, Baracat EC, Rodrigues de Lima G, Castello Girão MJ (February 2011). "Sexual steroids in urogynecology". Climacteric. 14 (1): 5–14. doi:10.3109/13697137.2010.508542. PMID   20839956. S2CID   32209654.
  9. ↑ Kim HK, Kang SY, Chung YJ, Kim JH, Kim MR (August 2015). "The Recent Review of the Genitourinary Syndrome of Menopause". Journal of Menopausal Medicine. 21 (2): 65–71. doi: 10.6118/jmm.2015.21.2.65 . PMC   4561742 . PMID   26357643.
  10. ↑ Lara LA, Useche B, Ferriani RA, Reis RM, de Sá MF, de Freitas MM, et al. (January 2009). "The effects of hypoestrogenism on the vaginal wall: interference with the normal sexual response". The Journal of Sexual Medicine. 6 (1): 30–9. doi:10.1111/j.1743-6109.2008.01052.x. PMID   19170834.
  11. ↑ Al-Badr A, Al-Shaikh G (August 2013). "Recurrent Urinary Tract Infections Management in Women: A review". Sultan Qaboos University Medical Journal. 13 (3): 359–67. doi:10.12816/0003256. PMC   3749018 . PMID   23984019.
  12. ↑ Meczekalski B, Podfigurna-Stopa A, Genazzani AR (2010). "Hypoestrogenism in young women and its influence on bone mass density". Gynecological Endocrinology. 26 (9): 652–657. doi:10.3109/09513590.2010.486452. ISSN   0951-3590. PMID   20504098. S2CID   26063411.
  13. ↑ Khosla S (September 2008). "Estrogen and bone: insights from estrogen-resistant, aromatase-deficient, and normal men". Bone. 43 (3): 414–7. doi:10.1016/j.bone.2008.05.005. PMC   2553890 . PMID   18567553.
  14. ↑ Latalski M, Danielewicz-Bromberek A, Fatyga M, Latalska M, Kröber M, Zwolak P (October 2017). "Current insights into the aetiology of adolescent idiopathic scoliosis". Archives of Orthopaedic and Trauma Surgery. 137 (10): 1327–1333. doi:10.1007/s00402-017-2756-1. PMC   5602042 . PMID   28710669.
  15. ↑ Office of the Surgeon General (US) (2004). Diseases of Bone. Office of the Surgeon General (US).
  16. 1 2 Alswat KA (May 2017). "Gender Disparities in Osteoporosis". J Clin Med Res. 9 (5): 382–387. doi:10.14740/jocmr2970w. PMC   5380170 . PMID   28392857.
  17. 1 2 Nelson LM (February 2009). "Clinical practice. Primary ovarian insufficiency". The New England Journal of Medicine. 360 (6): 606–14. doi:10.1056/nejmcp0808697. PMC   2762081 . PMID   19196677.
  18. 1 2 Richard-Eaglin A (September 1, 2018). "Male and Female Hypogonadism". Nursing Clinics of North America. Syndromes in Organ Failure. 53 (3): 395–405. doi:10.1016/j.cnur.2018.04.006. ISSN   0029-6465. PMID   30100005. S2CID   51966781.
  19. 1 2 3 Bhagavath B, Layman LC (2013). "Chapter 32 – Genetics of Female Infertility in Humans". In Rimoin D, Pyeritz R, Korf B (eds.). Emery and Rimoin's Principles and Practice of Medical Genetics. Oxford: Academic Press. pp. 1–24. ISBN   978-0-12-383834-6.
  20. ↑ Dubey R (2012). Sex Hormones. BoD – Books on Demand. p. 39. ISBN   978-953-307-856-4.
  21. 1 2 Gargus E, Deans R, Anazodo A, Woodruff TK (September 2018). "Management of Primary Ovarian Insufficiency Symptoms in Survivors of Childhood and Adolescent Cancer". J Natl Compr Canc Netw. 16 (9): 1137–1149. doi:10.6004/jnccn.2018.7023. PMC   6607891 . PMID   30181423.
  22. ↑ Gandhi J, Chen A, Dagur G, Suh Y, Smith N, Cali B, Khan SA (December 2016). "Genitourinary syndrome of menopause: an overview of clinical manifestations, pathophysiology, etiology, evaluation, and management". Am. J. Obstet. Gynecol. 215 (6): 704–711. doi: 10.1016/j.ajog.2016.07.045 . PMID   27472999.
  23. ↑ Kaur H, Merchant M, Haque MM, Mande SS (2020). "Crosstalk Between Female Gonadal Hormones and Vaginal Microbiota Across Various Phases of Women's Gynecological Lifecycle". Front Microbiol. 11: 551. doi: 10.3389/fmicb.2020.00551 . PMC   7136476 . PMID   32296412.
  24. ↑ Gordon CM, Ackerman KE, Berga SL, Kaplan JR, Mastorakos G, Misra M, Murad MH, Santoro NF, Warren MP (May 2017). "Functional Hypothalamic Amenorrhea: An Endocrine Society Clinical Practice Guideline". J. Clin. Endocrinol. Metab. 102 (5): 1413–1439. doi: 10.1210/jc.2017-00131 . PMID   28368518.
  25. ↑ Demers LM, Hankinson SE, Haymond S, Key T, Rosner W, Santen RJ, et al. (June 2015). "Measuring Estrogen Exposure and Metabolism: Workshop Recommendations on Clinical Issues". The Journal of Clinical Endocrinology and Metabolism. 100 (6): 2165–70. doi:10.1210/jc.2015-1040. PMC   5393513 . PMID   25850026.
  26. ↑ Shufelt CL, Torbati T, Dutra E (May 2017). "Hypothalamic Amenorrhea and the Long-Term Health Consequences". Seminars in Reproductive Medicine. 35 (3): 256–262. doi:10.1055/s-0037-1603581. PMC   6374026 . PMID   28658709.
  27. ↑ Sowińska-Przepiera E, Andrysiak-Mamos E, Jarząbek-Bielecka G, Walkowiak A, Osowicz-Korolonek L, Syrenicz M, et al. (2015). "Functional hypothalamic amenorrhoea — diagnostic challenges, monitoring, and treatment". Endokrynologia Polska. 66 (3): 252–60. doi: 10.5603/EP.2015.0033 . PMID   26136135.
  28. 1 2 3 4 Goodman NF, Cobin RH, Ginzburg SB, Katz IA, Woode DE (2011). "American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the diagnosis and treatment of menopause". Endocrine Practice. 17 Suppl 6 (Supplement 6): 1–25. doi: 10.4158/EP.17.S6.1 . PMID   22193047.
  29. ↑ Kaunitz AM, Manson JE (October 2015). "Management of Menopausal Symptoms". Obstet Gynecol. 126 (4): 859–76. doi:10.1097/AOG.0000000000001058. PMC   4594172 . PMID   26348174.
  30. 1 2 3 Simpson ER, Jones ME (2006). "Of mice and men: the many guises of estrogens". Ernst Schering Found Symp Proc (Review). Ernst Schering Foundation Symposium Proceedings. 2006/1 (1): 45–67. doi:10.1007/2789_2006_016. ISBN   978-3-540-49547-5. PMID   17824171.
  31. 1 2 3 Hammes SR, Levin ER (May 2019). "Impact of estrogens in males and androgens in females". J. Clin. Invest. (Review). 129 (5): 1818–1826. doi:10.1172/JCI125755. PMC   6486327 . PMID   31042159.
  32. 1 2 3 Cooke PS, Nanjappa MK, Ko C, Prins GS, Hess RA (July 2017). "Estrogens in Male Physiology". Physiol. Rev. (Review). 97 (3): 995–1043. doi:10.1152/physrev.00018.2016. PMC   6151497 . PMID   28539434.
  33. 1 2 Kacker R, Traish AM, Morgentaler A (June 2012). "Estrogens in men: clinical implications for sexual function and the treatment of testosterone deficiency". J Sex Med (Review). 9 (6): 1681–96. doi:10.1111/j.1743-6109.2012.02726.x. PMID   22512993.
  34. ↑ de Ronde W, de Jong FH (June 2011). "Aromatase inhibitors in men: effects and therapeutic options". Reprod. Biol. Endocrinol. (Review). 9: 93. doi: 10.1186/1477-7827-9-93 . PMC   3143915 . PMID   21693046.
  35. ↑ Russell N, Cheung A, Grossmann M (August 2017). "Estradiol for the mitigation of adverse effects of androgen deprivation therapy". Endocr. Relat. Cancer (Review). 24 (8): R297–R313. doi: 10.1530/ERC-17-0153 . PMID   28667081.
  36. ↑ Wibowo E, Wassersug RJ (September 2013). "The effect of estrogen on the sexual interest of castrated males: Implications to prostate cancer patients on androgen-deprivation therapy". Crit. Rev. Oncol. Hematol. (Review). 87 (3): 224–38. doi:10.1016/j.critrevonc.2013.01.006. PMID   23484454.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.