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Introduction
Cessation of menstruation with age.
Definitive when amenorrhea has lasted for 12 months.
Etiology
- failure of ovarian follicular development in the presence of sufficient gonadotropin levels
- gradual decline in ovarian function & estrogen production
- age at natural menopause unaffected by tubal ligation[54]
- pregnancy & breast-feeding may lower risk for early menopause[61]
Epidemiology
- average age of menopause is 51-52 years[49]
- range is 40-60 years
- smokers may have accelerated menopause
- 75-80% of women experience discomfort associated with menopause
- 10-15% experience symptoms that interfere with activities of daily living
- 25% complain of symptoms lasting more than 5 years
Pathology
- declining estrogen levels result in onset of accelerated bone loss
- skin thickness & collagen content are reduced, resulting in wrinkles
- urogenital atrophy
- mucosa of vagina becomes extremely sensitive to estrogen
- vaginal atrophy
- increased susceptibility to bacterial vaginitis
- vulvar & labial atrophy
- atrophy of urethra & bladder trigone
- atrophy of pelvic support increasing risk of uterine prolapse, cystocele & rectocele
- change in vaginal endogenous flora from Lactobacillus to Streptococcus & Prevotella[33]
- androgen deficiency may contribute to:[6]
- sarcopenia
- osteoporosis
- fatigue & psychological symptoms
- progressive increase in risk of coronary artery disease
- estrogen acts directly on coronary arteries inducing vasodilation
- estrogen inhibits development of atheromatous plaques by favorable effects on lipoprotein profile
- higher serum testosterone in postmenopausal women increases risk of cardiovascular disease[48]
- in contrast, higher serum estradiol in postmenopausal women associated with lower cardiovascular risk[48]
- carotid intima-media thickness & adventitial diameter increase in the perimenopausal period[25]
- cardiovascular disease may influence onset of menopause
Genetics
- common gene variants affecting timing of menopause:
- UK Biobank identified gene-based associations :
- 5 genes harbouring variants with large effects
- 4 genes associated with timing of menopause increase risk of cancer
- women homozygous for stop-gain variant rs117316434(A) in CCDC201 (p.(Arg162Ter) reached menopause 9 years earlier than other women
Clinical manifestations
- hypermenorrhea, oligomenorrhea & finally amenorrhea
- MKSAP19 would disagree (see below)#
- hot flashes* (16%)[7]
- mean duration 5.2 years[16]
- hot flashes often recurr after cessation of hormone replacement therapy (HRT)[11]
- night sweats
- vaginal dryness (26%)[7][17]
- genital irritation (10%)[7]
- urinary stress incontinence[9]
- symptoms of cystitis
- insomnia, early awakening, irritability &/or anxiety (46-53%)
- depression generally resolves within 1 year[28]
- arthralgias ?[26]
- weight gain NOT associated with menopause[4]
- low estrogen levels of menopause associated with nighttime hot flashes, sleep disturbance, & depression[43]
* the 2 manifestations that may be definitively attributed to menopause
# irregular menses with period lasting 15 days is anovulatory bleeding or abnormal vaginal bleeding warranting endometrial biopsy without transvaginal ultrasound in perimenopausal women according to MKSAP19[2]
Laboratory
- in general, diagnosis is clinical & no specific laboratory testing is required[2]
- for premature menopause (<40): serum FSH, serum TSH & serum prolactin[2]
- serum gonadotropins
- serum follicle-stimulating hormone (serum FSH) is increased generally > 40 mIU/mL
- serum luteinizing hormone (serum LH)
- during the perimenopausal period, LH levels remain in the high normal range
- serum LH levels reach a peak 1-3 years after the menopause followed by a gradual decline
- serum FSH/serum LH ratio > 1 suggestive of menopause
- Mullerian inhibiting substance in serum/plasma (PicoAMH Elisa)[52]
- serum estradiol levels tend to be diminished
- women on oral contraceptives
- home menopause test NOT recommended[8]
Diagnostic procedures
Complications
- osteoporosis
- early menopause leads to more osteoporotic fractures & earlier death[21]
- unintentional weight loss associated with highest risk of bone fracture in postmenopausal women[36]
- atherosclerosis[62]
- natural menopause before age 45
- 50% increased risk for coronary heart disease
- 19% increased risk for cardiovascular mortality
- 12% increased risk for overall mortality[42]
- premature & early menopause are risk factors for cardiovascular disease whether natural or surgical (RR = 1.6 to 1.8)[57][59]
- age of menopause not a cardiovascular risk factor[60]
- natural menopause before age 45
- sleep disturbance[31]
- depression[13][19] generally resolves within 1 year[28]
- sleep disturbance & depression increase cardiovascular risk[62]
- hot flashes may persist in older menopausal women in a minority of cases
- vasomotor symptoms of menopause are linked to dyslipidemia, insulin resistance, & hypertension[62]
- memory loss ?[15]
- increased risk of new-onset asthma (RR=3.4)[38]
- pregnancy is possible in the perimenopausal period even if menstrual cycles are irregular[2]
Management
- topical agents
- vaginal moisturizers or lubricants
- vaginal estrogen for atrophic vaginitis
- transdermal estradiol(Climara) 50 micrograms/day
- use in combination with progesterone if woman still has uterus
- oral agents
- hormone replacement therapy short term < 3 years
- estrogen is most effective therapy for vasomotor symptoms[2]
- indications:
- women < 60 years with 10 years of menopause[2]
- intolerable vasomotor symptoms
- low-dose estrogen may improve mood[23]
- urinary incontinence, decreased libido are NOT indications[2]
- may reduce cardiovascular risk when initiated during menopausal transition, but may be harmful when initiated > 10 years since menopause[62]
- contraindications:
- pregnancy, vaginal bleeding, liver disease, coronary artery disease, stroke venous thromboembolism, breast cancer, endometrial cancer
- chest wall radiation
- chemotherapy is not a contraindication[2]
- unopposed estrogen: Premarin 0.625 mg QD if woman has had hysterectomy
- cyclic therapy results in resumption of menses
- continuous therapy
- hot-flashes in estrogen-intolerant women
- chest wall radiation but not chemotherapy increases risk for breast cancer[2]
- Provera only
- megace 20 mg PO BID
- venlafaxine (Effexor): start 12.5 mg PO BID
- serotonin re-uptake inhibitors (SSRI)
- paroxetine (Paxil) 10-20 mg PO QD
- only nonhormonal medication approved in U.S.for treatment of vasomotor symptoms of menopause
- start 7.5 mg QHS, increase PRN to 25 mg QHS[56]
- fluoxetine (Prozac) 20 mg PO QD
- sertraline (Zoloft) 25-50 mg PO QD
- escitalopram (Lexapro) 10-20 mg PO QD[18]
- paroxetine (Paxil) 10-20 mg PO QD
- gabapentin (Neurontin): start 100 mg PO QHS (modest efficacy)[56]
- pregabalin[2]
- clonidine 0.05-0.2 mg BID[2] - little or no benefit[56]
- evaluate annually for continued need of therapy[2]
- hormone replacement therapy short term < 3 years
- diet & lifestyle
- lifestyle interventions may reduce cardiovascular risk[62]
- no evidence to support routine supplementation with calcium &/or vitamin D[22]
- soy protein enriched in isoflavones of limited benefit[9]
- oily fish & fresh legumes associated with a delay in menopause; refined pasta & rice associated with earlier menopause[46]
- medicinal herbs
- black cohosh[2] is questionable recommendation
- phytoestrogens
- modest benefit for hot flashes & vaginal dryness[41]
- no effect on night sweats
- soy isoflavones
- modest benefit for hot flashes & vaginal dryness[41]
- no value in preventing hot flashes or loss of bone mineral density[20]
- pine bark extract appears of benefit for hot flashes[41]
- chinese herbal remedies (dong quai) of no benefit[41]
- MKSAP 19 concludes herbal therapies of unproven benefit[2]
- exercise[27] - regular aerobic weight-bearing exercise
- may reduce risk of hip fractures & total fracture risk[58]
- may increase risk of knee fracture & arm or forearm fracture[58]
- cognitive behavioral therapy for insomnia due to hot flashes[45]
- mindfulness training, cognitive behavioral therapy, & behavior-based therapy helpful in relieving hot-flashes[47]
- acupuncture may help treat some symptoms (hot flashes, sleep, emotions)[53]
- patient education
- monthly self breast exam
- regular mammograms
- a mobile app from the North American Menopause Society[35]
- dysfunctional uterine bleeding in perimenopausal women
Clinical trials
- KEEPS trial reports that estrogen-progesterone treatment started soon after menopause
- relieves menopausal symptoms of hot flashes & night sweats
- improves mood
- improves bone mineral density
- improves sexual function
More general terms
More specific terms
Additional terms
- amenorrhea (oligomenorrhea)
- home menopause test
- hormone replacement therapy (HRT); estrogen replacement therapy; postmenopausal hormone replacement therapy
- hot flash; menopausal vasomotor symptom
References
- ↑ Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 451-53
- ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2009, 2018, 2022.
Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022 - ↑ Prescriber's Letter 7(8):44 2000
- ↑ 4.0 4.1 Journal Watch 20(10):80, 2000 Crawford et al Menopause 7:96, 2000
- ↑ Greendale et al Lancet 353:571, 1999
- ↑ 6.0 6.1 Solomon DH, in: UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
- ↑ 7.0 7.1 7.2 7.3 Journal Watch 23(3):28, 2003 Barnabei VM et al, Obstet Gynecol 100:1209, 2002
- ↑ 8.0 8.1 Prescriber's Letter 11(6):36 2004 Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=200615&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 9.0 9.1 9.2 Journal Watch 24(16):130, 2004 Kreijkamp-Kaspers S, Kok L, Grobbee DE, de Haan EH, Aleman A, Lampe JW, van der Schouw YT. Effect of soy protein containing isoflavones on cognitive function, bone mineral density, and plasma lipids in postmenopausal women: a randomized controlled trial. JAMA. 2004 Jul 7;292(1):65-74. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15238592
- ↑ NIH News NIH State-of-the-Science Panel Calls for 'Demedicalization' of Menopause http://www.nih.gov/news/pr/mar2005/od-23.htm
- ↑ 11.0 11.1 Journal Watch 25(17):134, 2005 Ockene JK, Barad DH, Cochrane BB, Larson JC, Gass M, Wassertheil-Smoller S, Manson JE, Barnabei VM, Lane DS, Brzyski RG, Rosal MC, Wylie-Rosett J, Hays J. Symptom experience after discontinuing use of estrogen plus progestin. JAMA. 2005 Jul 13;294(2):183-93. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16014592
Petitti DB. Some surprises, some answers, and more questions about hormone therapy: further findings from the Women's Health Initiative. JAMA. 2005 Jul 13;294(2):245-6. No abstract available. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16014599 - ↑ The role of testosterone therapy in postmenopausal women: position statement of The North American Menopause Society http://www.menopause.org/aboutmeno/PStestosterone.pdf corresponding NGC guideline withdrawn 12/10
- ↑ 13.0 13.1 Cohen LS et al, Risk for new onset of depression during the menopausal transition: The Harvard study of moods and cycles. Arch Gen Psychiatry 2006; 63:385 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16585467
Freeman EW et al, Associations of hormones and menopausal status with depressed mood in women with no history of depression Gen Psychiatry 2006; 63:375 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16585466 - ↑ Kok HS et al, Heart disease risk determines menopausal age rather than the reverse. J Am Coll Cardiol 2006; 47:1976 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16697313
Bittner V Menopause and cardiovascular risk. Cause of consequence? J Am Coll Cardiol 2006; 47:1984 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16697314 - ↑ 15.0 15.1 Henderson VW. The neurology of menopause. Neurologist. 2006 May;12(3):149-59. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16688016
- ↑ 16.0 16.1 Col NF et al Duration of vasomotor symptoms in middle-aged women: A longitudinal study. Menopause 2009 May/Jun; 16:453 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19188852
- ↑ 17.0 17.1 Avis NE et al Longitudinal changes in sexual functioning as women transition through menopause: Results from the Study of Women's Health Across the Nation. Menopause 2009 May/Jun; 16:442. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19212271
- ↑ 18.0 18.1 Freeman EW et al Efficacy of Escitalopram for Hot Flashes in Healthy Menopausal Women: A Randomized Controlled Trial JAMA. 2011;305(3):267-274 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21245182 <Internet> http://jama.ama-assn.org/content/305/3/267.short
- ↑ 19.0 19.1 Bromberger JT et al. Major depression during and after the menopausal transition: Study of Women's Health Across the Nation (SWAN). Psychol Med 2011 Feb 9 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21306662 <Internet> http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=8059759
- ↑ 20.0 20.1 Levis S et al. Soy isoflavones in the prevention of menopausal bone loss and menopausal symptoms: A randomized, double-blind trial. Arch Intern Med 2011 Aug 8/22; 171:1363 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21824950
- ↑ 21.0 21.1 Svejme O et al. Early menopause and risk of osteoporosis, fracture and mortality: A 34-year prospective observational study in 390 women. BJOG 2012 Jun; 119:810. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22531019
- ↑ 22.0 22.1 USPSTF Vitamin D and Calcium Supplementation to Prevent Cancer and Osteoporotic Fractures in Adults: U.S. Preventive Services Task Force Recommendation Statement: DRAFT http://www.uspreventiveservicestaskforce.org/draftrec3.htm
- ↑ 23.0 23.1 Suzuki H et al. Involvement of estrogen receptor beta in maintenance of serotonergic neurons of the dorsal raphe. Mol Psychiatry 2012 Jun 5 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22665260 <Internet> http://www.nature.com/mp/journal/vaop/ncurrent/full/mp201262a.html
Phan A et al. Low doses of 17beta-estradiol rapidly improve learning and increase hippocampal dendritic spines. Neuropsychopharmacology 2012 Jun 6 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22669167 <Internet> http://www.nature.com/npp/journal/vaop/ncurrent/full/npp201282a.html - ↑ KEEPS Reports Hormone Therapy Provides Quality of Life Benefits for Newly Menopausal Women North American Menopause Society 23rd Annual Meeting Oct 2012 http://www.menopause.org/annual-meetings/2012-meeting/keeps-report
- ↑ 25.0 25.1 El Khoudary SR et al. Progression rates of carotid intima-media thickness and adventitial diameter during the menopausal transition. Menopause 2013 Jan; 20:8. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22990755
Pai JK and Manson JE. Acceleration of cardiovascular risk during the late menopausal transition. Menopause 2013 Jan; 20:1 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23266836 - ↑ 26.0 26.1 Chlebowski RT et al. Estrogen alone and joint symptoms in the Women's Health Initiative randomized trial. Menopause 2013 Mar 18; PMID: https://www.ncbi.nlm.nih.gov/pubmed/23511705
Kaunitz AM. Should new-onset arthralgia be considered a menopausal symptom? Menopause 2013 Mar 18; PMID: https://www.ncbi.nlm.nih.gov/pubmed/23549444 - ↑ 27.0 27.1 Lambiase MJ and Thurston RC. Physical activity and sleep among midlife women with vasomotor symptoms. Menopause 2013 Sep; 20:946. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23531686
- ↑ 28.0 28.1 28.2 Freeman EW et al Longitudinal Pattern of Depressive Symptoms Around Natural Menopause. JAMA Psychiatry. Published online November 13, 2013 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24227182 <Internet> http://archpsyc.jamanetwork.com/article.aspx?articleid=1772342
- ↑ Martin KA, Manson JE. Approach to the patient with menopausal symptoms. J Clin Endocrinol Metab. 2008 Dec;93(12):4567-75. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19056840
- ↑ Prescriber's Letter 21(3): 2014 Postmenopausal Hormone Therapy CHART: Postmenopausal Hormone Therapy COMMENTARY: Nonhormonal Therapy for Hot Flashes COMMENTARY: New Drug: Osphena (Ospemifene) SPECIAL REPORT: Natural Medicines in the Clinical Management of Menopausal Symptoms Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=300310&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 31.0 31.1 Athappilly G and Joffe H Sleep Disturbances During the Menopausal Transition. NEJM Journal Watch. Women's Health. March 11, 2014 Massachusetts Medical Society http://www.jwatch.org/na33784/2014/03/11/sleep-disturbances-during-menopausal-transition (subscription may be needed) http://www.jwatch.org
- ↑ Huang AJ, Grady D, Jacoby VL Persistent hot flushes in older postmenopausal women. Arch Intern Med. 2008 Apr 28;168(8):840-6. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18443259
- ↑ 33.0 33.1 Brotman RM et al. Association between the vaginal microbiota, menopause status, and signs of vulvovaginal atrophy. Menopause 2014 May; 21:450 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24080849 <Internet> http://journals.lww.com/menopausejournal/pages/articleviewer.aspx?year=2014&issue=05000&article=00005&type=abstract
- ↑ North American Menopause Society http://www.menopause.org/aboutmeno/PScalcium.pdf
- ↑ 35.0 35.1 Manson JE et al. MenoPro: A mobile app for women bothered by menopause symptoms. Menopause 2014 Oct http://www.menopause.org/for-women/menopro-a-mobile-app-for-women-bothered-by-menopause-symptoms
- ↑ 36.0 36.1 Crandall CJ et al. Postmenopausal weight change and incidence of fracture: Post hoc findings from Women's Health Initiative observational study and clinical trials. BMJ 2015 Jan 27; 350:h25 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25627698 <Internet> http://www.bmj.com/content/350/bmj.h25
- ↑ Agency for Healthcare Research and Quality Menopausal Symptoms: Comparative Effectiveness of Therapies. Research Review - Final - Mar. 5, 2015 http://www.effectivehealthcare.ahrq.gov/search-for-guides-reviews-and-reports/?pageaction=displayproduct&productID=2051
- ↑ 38.0 38.1 Triebner K, Johannessen A, Puggini L et al. Menopause as a predictor of new-onset asthma: A longitudinal Northern European population study. J Allergy Clin Immunol 2016 Jan; 137:50. PMID: https://www.ncbi.nlm.nih.gov/pubmed/26435006
- ↑ Manson JE, Kaunitz AM Menopause Management - Getting Clinical Care Back on Track. N Engl J Med 2016; 374:803-806. March 3, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26348174 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMp1514242
- ↑ American College of Obstetricians and Gynecologists (ACOG) ACOG Practice Bulletin No. 141: Management of menopausal symptoms. Obstet Gynecol. 2014 Jan;123(1):202-16 PMID: https://www.ncbi.nlm.nih.gov/pubmed/24463691
- ↑ 41.0 41.1 41.2 41.3 41.4 41.5 Franco OH, Chowdhury R, Troup J Use of Plant-Based Therapies and Menopausal Symptoms. A Systematic Review and Meta-analysis. JAMA. 2016;315(23):2554-2563 PMID: https://www.ncbi.nlm.nih.gov/pubmed/2732780
- ↑ 42.0 42.1 Muka T, Oliver-Williams C, Kunutsor S et al Association of Age at Onset of Menopause and Time Since Onset of Menopause With Cardiovascular Outcomes, Intermediate Vascular Traits, and All-Cause MortalityA Systematic Review and Meta-analysis. JAMA Cardiol. Published online September 14, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27627190 <Internet> http://cardiology.jamanetwork.com/article.aspx?articleid=2551981
Manson JE, Woodruff TK Reproductive Health as a Marker of Subsequent Cardiovascular Disease. The Role of Estrogen. JAMA Cardiol. Published online September 14, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27626902 <Internet> http://cardiology.jamanetwork.com/article.aspx?articleid=2551979 - ↑ 43.0 43.1 Joffe H, Crawford SL, Freeman MP et al Independent Contributions of Nocturnal Hot Flashes and Sleep Disturbance to Depression in Estrogen-Deprived Women. J Clin Endocrinol Metab. 2016 Oct;101(10):3847-3855. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27680875
- ↑ Rahimikian F, Rahimi R, Golzareh P, Bekhradi R, Mehran A. Effect of Foeniculum vulgare Mill. (fennel) on menopausal symptoms in postmenopausal women: a randomized, triple-blind, placebo-controlled trial. Menopause. May 15, 2017 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28509813 <Internet> http://journals.lww.com/menopausejournal/Abstract/publishahead/Effect_of_Foeniculum_vulgare_Mill___fennel__on.97782.aspx
- ↑ 45.0 45.1 Guthrie KA, Larson JC, Ensrud KE et al. Effects of pharmacologic and nonpharmacologic interventions on insomnia symptoms and subjective sleep quality in women with hot flashes: A pooled analysis of individual participant data from 4 MsFLASH trials. Sleep 2017 Nov 20 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29165623 https://academic.oup.com/sleep/advance-article-abstract/doi/10.1093/sleep/zsx190/4642822?redirectedFrom=fulltext
- ↑ 46.0 46.1 Dunneram Y, Greenwood DC, Burley VJ, Cade JE. Dietary intake and age at natural menopause: results from the UK Women's Cohort Study. J Epidemiol Community Health 2018 Apr 30 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29712719 Free full text <Internet> http://jech.bmj.com/content/early/2018/04/10/jech-2017-209887
- ↑ 47.0 47.1 van Driel C, Stuursma AS, Schroevers MJ, Mourits M, de Bock GH. Mindfulness, cognitive behavioural and behaviour-based therapy for natural and treatment-induced menopausal symptoms: A systematic review and meta-analysis. BJOG 2018 Mar 15 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29542222
- ↑ 48.0 48.1 48.2 Zhao D, Guallar E, Ouyang P et al Endogenous Sex Hormones and Incident Cardiovascular Disease in Post-Menopausal Women. J Am Coll Cardiol 71(22): June 2018 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29852978 <Internet> http://www.onlinejacc.org/content/71/22/2555
Miller VM, Mankad R Sex Steroids and Incident Cardiovascular Disease in Post- Menopausal Women. New Perspective on an Old Controversy. J Am Coll Cardiol 71(22): June 2018 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29852979 <Internet> http://www.onlinejacc.org/content/71/22/2567 - ↑ 49.0 49.1 49.2 Kuh D, Cooper R, Moore A, Richards M, Hardy R. Age at menopause and lifetime cognition: Findings from a British birth cohort study. Neurology 2018 May 8; 90:e1673 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29643079 Free PMC Article <Internet> http://n.neurology.org/content/90/19/e1673
- ↑ Grady D. Clinical practice. Management of menopausal symptoms. N Engl J Med 2006 Dec 1; 355:2338 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17135587 Free full text https://www.nejm.org/doi/full/10.1056/NEJMcp054015
- ↑ Stuenkel CA, Davis SR, Gompel A et al. Treatment of symptoms of the menopause: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2015 Nov; 100:3975-4011. PMID: https://www.ncbi.nlm.nih.gov/pubmed/26444994
- ↑ 52.0 52.1 FDA News Release. Oct 24, 2019 FDA permits marketing of a diagnostic test to aid in the determination of menopausal status. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm624284.htm
- ↑ 53.0 53.1 Lund KS, Siersma V, Brodersen J, Waldorff FB. Efficacy of a standardised acupuncture approach for women with bothersome menopausal symptoms: a pragmatic randomised study in primary care (the ACOM study). BMJ Open. 9(1) 2019 https://bmjopen.bmj.com/content/9/1/e023637
- ↑ 54.0 54.1 Ainsworth AJ et al. Tubal ligation and age at natural menopause. Obstet Gynecol 2019 Jun; 133:1247. PMID: https://www.ncbi.nlm.nih.gov/pubmed/31135741 https://insights.ovid.com/crossref?an=00006250-201906000-00024
- ↑ Santoro N, Johnson J. Diagnosing the Onset of Menopause. JAMA. Published online July 22, 2019 (Multimedia) PMID: https://www.ncbi.nlm.nih.gov/pubmed/31329213 https://jamanetwork.com/journals/jama/fullarticle/2739289
- ↑ 56.0 56.1 56.2 56.3 NEJM Knowledge+ Question of the Week. Sept 24, 2019 https://knowledgeplus.nejm.org/question-of-week/1760/
Carroll DG, Lisenby KM, Carter TL. Critical appraisal of paroxetine for the treatment of vasomotor symptoms. Int J Womens Health 2015; 7:615 PMID: https://www.ncbi.nlm.nih.gov/pubmed/26124682 Free PMC Article
Pinkerton JV, Joffe H, Kazempour K, Mekonnen H, Bhaskar S, Lippman J. Low-dose paroxetine (7. 5 mg) improves sleep in women with vasomotor symptoms associated with menopause. Menopause 2015 Jan; 22:50. PMID: https://www.ncbi.nlm.nih.gov/pubmed/25137243 Free PMC Article - ↑ 57.0 57.1 Zhu D, Chung HF, Dobson AJ et al. Age at natural menopause and risk of incident cardiovascular disease: A pooled analysis of individual patient data. Lancet Public Health 2019 Oct 3; PMID: https://www.ncbi.nlm.nih.gov/pubmed/31588031 Free Article https://www.thelancet.com/journals/lanpub/article/PIIS2468-2667(19)30155-0/fulltext
- ↑ 58.0 58.1 58.2 LaMonte MJ, Wactawski-Wende et al. Association of physical activity and fracture risk among postmenopausal women. JAMA Netw Open 2019 Oct 2; 2:e1914084 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31651972 Free PMC Article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2753526
- ↑ 59.0 59.1 Honigberg MC et al. Association of premature natural and surgical menopause with incident cardiovascular disease. JAMA 2019 Nov 18 PMID: https://www.ncbi.nlm.nih.gov/pubmed/1738818 https://jamanetwork.com/journals/jama/article-abstract/2755841
- ↑ 60.0 60.1 O'Keeffe LM, Kuh D, Fraser A et al Age at period cessation and trajectories of cardiovascular risk factors across mid and later life Heart. Feb 2020 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32098806 Free Article https://heart.bmj.com/content/early/2020/01/31/heartjnl-2019-315754
Gersh FL, Lasvie CJ Menopause and hormone replacement therapy in the 21st century Heart. Feb 2020 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32098805 https://heart.bmj.com/content/early/2020/01/31/heartjnl-2019-315898 - ↑ 61.0 61.1 Langton CR, Whitcomb BW, Purdue-Smithe AC et al. Association of parity and breastfeeding with risk of early natural menopause. JAMA Netw Open 2020 Jan 3; 3:e1919615 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31968114 Free PMC Article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2759124
- ↑ 62.0 62.1 62.2 62.3 62.4 62.5 El Khoudary SR et al. Menopause transition and cardiovascular disease risk: Implications for timing of early prevention: A scientific statement from the American Heart Association. Circulation 2020 Dec 22; 142:e506 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33251828 https://www.ahajournals.org/doi/10.1161/CIR.0000000000000912
- ↑ Crandall CJ, Mehta JM, Manson JE Management of Menopausal Symptoms. A Review. JAMA. 2023;329(5):405-420 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36749328 https://jamanetwork.com/journals/jama/fullarticle/2801054
- ↑ Burger HG. Unpredictable endocrinology of the menopause transition: clinical, diagnostic and management implications. Menopause Int. 2011;17:153-4. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22120939
- ↑ McNeil MA, Merriam SB. Menopause. Ann Intern Med. 2021;174:ITC97-ITC112. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34251902
- ↑ 66.0 66.1 66.2 66.3 Ledford H Why some women enter menopause early - and how that could affect their cancer risk. Nature. 11 September 2024 PMID: https://www.ncbi.nlm.nih.gov/pubmed/39261698 https://www.nature.com/articles/d41586-024-02905-5
Stankovic S, Shekari S, Huang QQ et al Genetic links between ovarian ageing, cancer risk and de novo mutation rates. Nature. 2024 Sep 11. PMID: https://www.ncbi.nlm.nih.gov/pubmed/39261734 https://www.nature.com/articles/s41586-024-07931-x
Oddsson A, Steinthorsdottir V, Oskarsson GR et al Homozygosity for a stop-gain variant in CCDC201 causes primary ovarian insufficiency. Nat Genet. 2024 Sep;56(9):1804-1810. PMID: https://www.ncbi.nlm.nih.gov/pubmed/39192094 https://www.nature.com/articles/s41588-024-01885-6 - ↑ British Menopause Society http://www.thebms.org.uk/