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==<big>Overview</big>==
==<big>Overview</big>==
Menopause is natural amenorrhea that is happened without any pathological causes, but premature menopause caused by pathological diseases, that are lead to early cessation of menses.
[[Menopause]] is natural [[amenorrhea]] that is happened without any [[pathological]] causes, but [[premature menopause]]/[https://www.healthline.com/health/menopause/causes-early early menopause] is caused by [[pathological]] [[diseases]] in [[ovaries]] and other [[organs]] such as [[premature ovarian failure]] ([https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2762081/ Primary ovarian insufficiency, POI)],  [[Adrenal insufficiency]], type1 [[diabetes mellitus]], [[Autoimmune thyroid diseases|autoimmune thyroid disease]], [[Fanconi anemia|Fanconi’s anemia]], and [[Congenital adrenal hyperplasia]]. [[Cardiovascular disease]] and [[Osteoporosis|osteoporosis]] are most important [[conditions]] associated with [[menopause]]. [[Women]] who had [[genetic disorders]] ( [[Fragile X syndrome]], [https://www.mayoclinic.org/diseases-conditions/turner-syndrome/symptoms-causes/syc-20360782#:~:text=Overview,to%20develop%20and%20heart%20defects. Turner’s syndrome])  more prone able to [https://www.healthline.com/health/menopause/causes-early early menopause]. The [[histopathological]] analysis include [[ovaries]]'s [[cortex]] becomes thinner and it has fewer [[Follicle|follicles]] and the [[medulla|medull]][[medulla|a]] develops  [[fibrosis]] and [[scars]]. Decrease of [[ciliated]] [[cells]] of  [[Fallopian tubes]] and [[Uterus]]. And [[atrophy]] of [[Vagina|vaginal mucosal layer]] .  


== <big>Pathophysiology</big> ==
==<big>Pathophysiology</big>==


==== <big>physiological  menopause:</big> ====
===Physiological menopause===
Menopause happens normally as women age, And the main cause of the menopause is the natural depletion of the primary follicles ([[oocytes]]) in the [[ovaries]] and And the decline of the response of ovaries to anterior pituitary gonads hormones that include [[Follicle Stimulating Hormone]] (FSH) and [[Luteinizing Hormone]](LH). These hormones stimulate the ovaries to produce [[estrogen]] and [[progesterone]] hormones in a cyclic pattern under the control of the [[hypothalamus]] that produces the gonadotropin-releasing hormones which stimulate anterior pituitary gonads hormone secretion and [[Inhibin|inhibin-B]] that plays role in feedback mechanism. '''"'''During perimenopause (approaching menopause), estradiol levels and patterns of production remain relatively unchanged or may increase compared to young women, but the cycles become frequently shorter or irregular. The often observed increase in estrogen is presumed to be in response to elevated FSH levels that, in turn, is hypothesized to be caused by decreased feedback by inhibin'''"'''.<ref>https://en.wikipedia.org/wiki/Menopause#Mechanism</ref> "Characteristic changes in the hypothalamic-pituitary-ovarian (HPO) axis during the menopause transition result from decreased ovarian feedback of inhibin and estradiol and are manifested primarily as elevations in follicle-stimulating hormone (FSH). Although central mechanisms may contribute to reproductive aging, they are less well characterized. Adrenal changes concurrent with the menopause transition include elevations in serum [[cortisol]] and transient elevations in [[dehydroepiandrosterone sulfate]], androstenediol, and other adrenal [[Androgen|androgens]]"<ref>http://www.menopause.org/docs/default-source/2014/nams-recomm-for-clinical-care.pdf</ref>. Post-menopause can be determined by a blood test that can reveal the very high levels of [[Follicle Stimulating Hormone]] (FSH) that are typical of post-menopausal women.


==== <big>pathological menopause</big>: ====
*[[Menopause]] happens normally as [[women]] [[age]] and the main cause of the [[menopause]] is the natural shortage of the primordial follicles ([[oocytes]]) that stored in the [[ovaries]] and the decrease of the response of [[ovaries]] to [https://en.wikipedia.org/wiki/Hypothalamic%E2%80%93pituitary%E2%80%93gonadal_axis#:~:text=The%20anterior%20portion%20of%20the,gonads%20produce%20estrogen%20and%20testosterone. anterior pituitary gonads hormones] that include [[Follicle Stimulating Hormone]] ([[FSH]]) and [[Luteinizing Hormone]]([[LH]]).
premature or early menopause induced by pathological disease in ovaries such as [[polycystic ovary syndrome]],  due to excessive secretion of [[androgen]] from ovaries lead to irregular cycle or amenorrhea. And [[autoimmune diseases]], the body’s immune system attacks the ovaries and keeps them from making hormones. [[Premature ovarian failure]] is the loss of ovarian function lead to amenorrhea because of ovarian failure to respond for gonads hormone ( FSH, LH) and deficiency production of estrogen and progesterone. [[Ovarian tumor]] or [[Endometriosis (female)|endometriosis]] that is required surgical intervention as Bilateral [[oophorectomy]] or salpingo-oophorectomy, the menstrual cycle will stop after this surgery, and hormone levels will drop quickly with strong menopausal symptoms. Bilateral oophorectomy sometimes was done with [[Hysterectomy]].
*These [[hormones]] stimulate the [[ovaries]] to produce [[estrogen]] and [[progesterone]] [[hormones]] in a cyclic method under the control of the [[hypothalamus]] that produces the [https://www.yourhormones.info/hormones/gonadotrophin-releasing-hormone/ gonadotropin-releasing hormones] which stimulate [https://en.wikipedia.org/wiki/Hypothalamic%E2%80%93pituitary%E2%80%93gonadal_axis#:~:text=The%20anterior%20portion%20of%20the,gonads%20produce%20estrogen%20and%20testosterone. anterior pituitary gonads hormone] secretion and [[Inhibin|inhibin-B]] that plays role in the [[feedback mechanism]].
*The [https://en.wikipedia.org/wiki/Hypothalamic%E2%80%93pituitary%E2%80%93gonadal_axis#:~:text=The%20anterior%20portion%20of%20the,gonads%20produce%20estrogen%20and%20testosterone. anterior pituitary gonads hormones] is decreased during the [[menopause]] transition result from decreased [[ovarian]] [[feedback]] of [[inhibin]]  and are manifested primarily as elevations in [[follicle-stimulating hormone]] ([[FSH]]).<ref name="pmid951489">{{cite journal| author=Mason AS| title=The menopause: the events of the menopause. | journal=R Soc Health J | year= 1976 | volume= 96 | issue= 2 | pages= 70-1 | pmid=951489 | doi=10.1177/146642407609600208 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=951489  }} </ref>


Hysterectomy does not itself cause menopause, although pelvic surgery can sometimes precipitate somewhat earlier menopause, perhaps because of compromised blood supply to the [[ovaries]], women who have undergone hysterectomy with ovary conservation go through menopause 3.7 years earlier than average.<ref>https://en.wikipedia.org/wiki/Menopause#Causes</ref>
===Premature menopause===
[[Premature menopause]]/[https://www.healthline.com/health/menopause/causes-early early menopause] is caused by several [[pathological]] [[diseases]] include:


== <big>Genetic</big> ==
*[[Pathological]] [[disease]] in ovaries include [[premature ovarian failure]] termed as [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2762081/ primary ovarian insufficiency (POI)]. It is the loss of [[ovarian]] function lead to [[amenorrhea]] because of [[ovarian failure]] to respond for [https://courses.lumenlearning.com/boundless-biology/chapter/endocrine-glands/#:~:text=Endocrine%20system%3A%20gonads%20and%20their,prepare%20the%20body%20for%20childbirth. gonads hormone] ( [[FSH]], [[LH]]) and deficiency production of [[estrogen]] and [[Progesterone|progesterone hormone]].
*[[Pathological]] [[disease]] in other [[organs]] such as  [[Adrenal insufficiency]], type1 [[Diabetes mellitus]], [[Autoimmune thyroid diseases|Autoimmune thyroid disease]], [[Fanconi anemia|Fanconi’s anemia]], [[Congenital adrenal hyperplasia]] due to [[17α-hydroxylase|17''α''-hydroxylase]] deficiency.<ref name="pmid27377497">{{cite journal| author=Hernández-Angeles C, Castelo-Branco C| title=Early menopause: A hazard to a woman's health. | journal=Indian J Med Res | year= 2016 | volume= 143 | issue= 4 | pages= 420-7 | pmid=27377497 | doi=10.4103/0971-5916.184283 | pmc=4928547 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27377497  }} </ref><ref>{{cite journal| author=Okeke T, Anyaehie U, Ezenyeaku C| title=Premature menopause. | journal=Ann Med Health Sci Res | year= 2013 | volume= 3 | issue= 1 | pages= 90-5 | pmc=3634232 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23634337  }} </ref>


*Fragile X syndrome gene is a genetic disorder characterized by reduction of ovarian function, women that have fragile x syndrome go through early menopause an average 5 years early than other women.
*Turner’s syndrome: Women born with missing chromosomes or problems with chromosomes can go through menopause early, women are born without all or part of one X chromosome, so their ovaries do not form normally at birth and their menstrual cycles, including the time around menopause, may not be normal.
__NOTOC__
{{Menopause}}
== Associated Conditions[edit | edit source] ==


*The most important Conditions associated with Menopause include:
==<big>Genetic</big>==
# Cardiovascular disease: " Estrogen has a positive effect on the tunica intima of the artery wall, helping to keep blood vessels flexible. During menopause, estrogen deficiency causes vasoconstriction of the vessel wall and an accelerated increase of low-density lipoprotein (LDL). Thus, menopause is linked to the increased risk of cardiovascular disease".
There are [[genetic disorders]] involved in the [[Premature ovarian failure|premature menopause]]/[https://www.healthline.com/health/menopause/causes-early early menopause]  include:
#Osteoporosis is a disease of the bones that causes bones to become weak and break easily." During menopause, estrogen deficiency increases osteoclastic activity, such that there is an imbalance of osteoclastic and osteoblastic activity. This results in more bone being reabsorbed and overall bone loss.  Estrogen deficiency leads to the release of cytokines among them RANKK ligand (RANKL), which plays a critical role in the osteoclastogenesis cascade. During menopause, women experience an increased rate of bone loss of 3% to 5% per year for 5 to 7 years".<ref>https://www.ncbi.nlm.nih.gov/books/NBK507826/#!po=10.0000</ref>


*[[Fragile X syndrome]] is a [[genetic disorder]] characterized by reduction of [[ovarian]] function, women that have [[Fragile X syndrome|Fragile X Syndrome]] go through [https://www.healthline.com/health/menopause/causes-early early menopause] an average 5 years early than other [[women]].<ref name="pmid12398227">{{cite journal| author=Laml T, Preyer O, Umek W, Hengstschlager M, Hanzal H| title=Genetic disorders in premature ovarian failure. | journal=Hum Reprod Update | year= 2002 | volume= 8 | issue= 5 | pages= 483-91 | pmid=12398227 | doi=10.1093/humupd/8.5.483 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12398227  }} </ref>
*[https://www.mayoclinic.org/diseases-conditions/turner-syndrome/symptoms-causes/syc-20360782#:~:text=Overview,to%20develop%20and%20heart%20defects. Turner’s syndrome]: [[women]] born with missing [[X chromosome]] can go through [[menopause]] early, due to their [[ovaries]] do not form normally at [[birth]].<ref name="pmid12773939">{{cite journal| author=Santoro N| title=Mechanisms of premature ovarian failure. | journal=Ann Endocrinol (Paris) | year= 2003 | volume= 64 | issue= 2 | pages= 87-92 | pmid=12773939 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12773939  }} </ref>


==<big>Associated Conditions</big>==
The most important [[Conditions]] associated with [[Menopause]] include:


== <big>Microscopic Pathology</big> ==
*[[Cardiovascular disease]]: during [[menopause]], [[estrogen]] deficiency causes [[vasoconstriction]] of the [[Blood vessel|vessel wall]]. [[menopause]] is linked to the increased risk of [[cardiovascular disease]].
On microscopic histopathological of menopause," Structures of the ovaries ( cortex and medulla)  are change, the distinction between the cortex and medulla is less evident  The cortex becomes thinner, it has fewer follicles that is the tendency towards the fragmentation of the corpora arenacea. Additionally, there are invaginations of the surface epithelium of the cortex, and epithelial inclusion cysts are present. The medulla develops stromal fibrosis and scars. The medulla also undergoes the hyalinization of vessel walls, with architectural changes of vessels. There is also a significant change in the vagina during menopause, the mucosa layer of the vagina begins to atrophy due to decreased estrogen that causes this cell layer to become drier and thinner. As a result, the vaginal mucosa loses its elasticity and becomes fragile".<ref>https://www.ncbi.nlm.nih.gov/books/NBK507826/#!po=10.0000</ref>


*[[Osteoporosis]] is a [[disease]] of the [[bones]] that causes [[bones]] to become weak and break easily. During [[menopause]], [[estrogen]] deficiency increases [https://support.clearcorrect.com/hc/en-us/articles/203836908-Osteoclastic-and-Osteoblastic-Activity#:~:text=Osteoclastic%20activity%20refers%20to%20the,allowing%20the%20tooth%20to%20move. osteoclastic activity].<ref name="pmid24969415">{{cite journal| author=Lobo RA, Davis SR, De Villiers TJ, Gompel A, Henderson VW, Hodis HN | display-authors=etal| title=Prevention of diseases after menopause. | journal=Climacteric | year= 2014 | volume= 17 | issue= 5 | pages= 540-56 | pmid=24969415 | doi=10.3109/13697137.2014.933411 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24969415  }} </ref>


==<big>Microscopic Pathology</big>==
On microscopic [[histopathological]] analysis of [[menopause]] include:
*[[Ovaries]]: the [[ovaries]]’s structure are change, the difference between the [[cortex]] and [[medulla]] is less evident. The [[cortex]] becomes thinner, it has fewer [[Follicle|follicles]].  And there are invaginations of the surface [[epithelium]] of the [[cortex]].The [[medulla]] develops [[fibrosis]] and [[scars]],  also undergoes the [[Hyaline|hyalinization]] of [[Vessel wall|vessel walls]].
*[[Fallopian tubes]] and [[Uterus]]: both [[endometrial]] and [[Fallopian tube|tubal]] [[mucosa]] demonstrated a gradual decrease in the number of [[ciliated]] [[cells]] and the non ciliated [[cells]] of the [[uterus]].
*[[Vagina]]: the [[mucosa]] layer begins to [[atrophy]] due to decreased [[estrogen]] that causes this layer to become drier and thinner.<ref name="pmid25410301">{{cite journal| author=Zerbinati N, Serati M, Origoni M, Candiani M, Iannitti T, Salvatore S | display-authors=etal| title=Microscopic and ultrastructural modifications of postmenopausal atrophic vaginal mucosa after fractional carbon dioxide laser treatment. | journal=Lasers Med Sci | year= 2015 | volume= 30 | issue= 1 | pages= 429-36 | pmid=25410301 | doi=10.1007/s10103-014-1677-2 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25410301  }} </ref><ref name="pmid11907929">{{cite journal| author=Makabe S, Motta PM, Naguro T, Vizza E, Perrone G, Zichella L| title=Microanatomy of the female reproductive organs in postmenopause by scanning electron microscopy. | journal=Climacteric | year= 1998 | volume= 1 | issue= 1 | pages= 63-71 | pmid=11907929 | doi=10.3109/13697139809080683 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11907929  }} </ref>





Latest revision as of 04:21, 22 February 2021

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Rahmah Al-Edresi, M.D.[2]

Overview

Menopause is natural amenorrhea that is happened without any pathological causes, but premature menopause/early menopause is caused by pathological diseases in ovaries and other organs such as premature ovarian failure (Primary ovarian insufficiency, POI), Adrenal insufficiency, type1 diabetes mellitus, autoimmune thyroid disease, Fanconi’s anemia, and Congenital adrenal hyperplasia. Cardiovascular disease and osteoporosis are most important conditions associated with menopause. Women who had genetic disorders ( Fragile X syndrome, Turner’s syndrome) more prone able to early menopause. The histopathological analysis include ovaries's cortex becomes thinner and it has fewer follicles and the medulla develops fibrosis and scars. Decrease of ciliated cells of Fallopian tubes and Uterus. And atrophy of vaginal mucosal layer .

Pathophysiology

Physiological menopause

Premature menopause

Premature menopause/early menopause is caused by several pathological diseases include:


Genetic

There are genetic disorders involved in the premature menopause/early menopause include:

Associated Conditions

The most important Conditions associated with Menopause include:

Microscopic Pathology

On microscopic histopathological analysis of menopause include:





References

  1. Mason AS (1976). "The menopause: the events of the menopause". R Soc Health J. 96 (2): 70–1. doi:10.1177/146642407609600208. PMID 951489.
  2. Hernández-Angeles C, Castelo-Branco C (2016). "Early menopause: A hazard to a woman's health". Indian J Med Res. 143 (4): 420–7. doi:10.4103/0971-5916.184283. PMC 4928547. PMID 27377497.
  3. Okeke T, Anyaehie U, Ezenyeaku C (2013). "Premature menopause". Ann Med Health Sci Res. 3 (1): 90–5. PMC 3634232.
  4. Laml T, Preyer O, Umek W, Hengstschlager M, Hanzal H (2002). "Genetic disorders in premature ovarian failure". Hum Reprod Update. 8 (5): 483–91. doi:10.1093/humupd/8.5.483. PMID 12398227.
  5. Santoro N (2003). "Mechanisms of premature ovarian failure". Ann Endocrinol (Paris). 64 (2): 87–92. PMID 12773939.
  6. Lobo RA, Davis SR, De Villiers TJ, Gompel A, Henderson VW, Hodis HN; et al. (2014). "Prevention of diseases after menopause". Climacteric. 17 (5): 540–56. doi:10.3109/13697137.2014.933411. PMID 24969415.
  7. Zerbinati N, Serati M, Origoni M, Candiani M, Iannitti T, Salvatore S; et al. (2015). "Microscopic and ultrastructural modifications of postmenopausal atrophic vaginal mucosa after fractional carbon dioxide laser treatment". Lasers Med Sci. 30 (1): 429–36. doi:10.1007/s10103-014-1677-2. PMID 25410301.
  8. Makabe S, Motta PM, Naguro T, Vizza E, Perrone G, Zichella L (1998). "Microanatomy of the female reproductive organs in postmenopause by scanning electron microscopy". Climacteric. 1 (1): 63–71. doi:10.3109/13697139809080683. PMID 11907929.


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