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Pros and Cons of Hormonal Replacement Therapy
Hormonal Replacement Therapy has emerged as the most controversial term in the field of Medical science ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"uu6gGvCG","properties":{"formattedCitation":"(Warren and Halpert)","plainCitation":"(Warren and Halpert)","noteIndex":0},"citationItems":[{"id":220,"uris":["http://zotero.org/users/local/CKNkWnK9/items/9ESHRHTA"],"uri":["http://zotero.org/users/local/CKNkWnK9/items/9ESHRHTA"],"itemData":{"id":220,"type":"article-journal","title":"Hormone replacement therapy: controversies, pros and cons","container-title":"Best Practice & Research Clinical Endocrinology & Metabolism","page":"317-332","volume":"18","issue":"3","source":"DOI.org (Crossref)","DOI":"10.1016/j.beem.2004.02.005","ISSN":"1521690X","title-short":"Hormone replacement therapy","journalAbbreviation":"Best Practice & Research Clinical Endocrinology & Metabolism","language":"en","author":[{"family":"Warren","given":"Michelle P"},{"family":"Halpert","given":"Sari"}],"issued":{"date-parts":[["2004",9]]}}}],"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"} (Warren and Halpert). It refers to a treatment that contributes towards the relief of symptoms associated with the menopause. This is usually accomplished with the replacement of hormones that are lost in the menopause. These include Estrogen and Progesterone; therefore, the therapy comprises a replacement of both. The research paper analyses the pros and cons of Hormonal Replacement Therapy derived from credible sources.
Pros of a Hormonal Replacement Therapy
The foremost advantage of Hormonal Replacement Therapy is the relief of symptoms experienced by menopausal women. These symptoms are very disturbing and have a major impact on a woman's life. Below stated are the possible HRT effects on a female body that have contributed towards its popularity.
Relief of hot flushes
Hot flushes are the most common symptom of menopause, which results in sleep disorders and impaired mental health. HRT has proved to be 90% effective in contributing to the relief of hot flushes. Many women have considered the Hormonal Replacement Therapy and are reported to get cured of Hot flashes which have improved their physical and mental health ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"OCcGBzS6","properties":{"formattedCitation":"(Scharf et al.)","plainCitation":"(Scharf et al.)","noteIndex":0},"citationItems":[{"id":231,"uris":["http://zotero.org/users/local/CKNkWnK9/items/PFVWCTE8"],"uri":["http://zotero.org/users/local/CKNkWnK9/items/PFVWCTE8"],"itemData":{"id":231,"type":"article-journal","title":"Effects of estrogen replacement therapy on rates of cyclic alternating patterns and hot-flush events during sleep in postmenopausal women: a pilot study","container-title":"Clinical Therapeutics","page":"304-311","volume":"19","issue":"2","source":"ScienceDirect","abstract":"The objective of this pilot study was to evaluate the effects of conjugated estrogens on the rates of cyclic alternating patterns of sleep (CAPS) and nocturnal hot flushes in symptomatic postmenopausal women. Seven postmenopausal or post-hysterectomy women aged 45 to 60 years with nocturnal diaphoresis and/or hot flushes participated in this study. The study was conducted with a single-masked design using a matching placebo. The placebo baseline was followed by a 4-week, single-masked treatment of conjugated estrogens 0.625 mg taken 4 hours before bedtime. Each patient's sleep was monitored in the laboratory for 3 consecutive nights during placebo baseline and again for 3 consecutive nights after an at-home period of at least 24 days of estrogen replacement therapy. Estrogen therapy resulted in a statistically significant decrease in the overall number of hot flushes and the number of hot flushes associated with awakenings, as well as improvement in sleep efficiency and a reduction in the rate of CAPS. These data confirm earlier well-established reports that estrogens reduce the frequency of hot flushes and suggest that the frequency of nocturnal arousals decreases and sleep quality improves in conjunction with a reduction in the rate of CAPS.","DOI":"10.1016/S0149-2918(97)80118-X","ISSN":"0149-2918","title-short":"Effects of estrogen replacement therapy on rates of cyclic alternating patterns and hot-flush events during sleep in postmenopausal women","journalAbbreviation":"Clinical Therapeutics","language":"en","author":[{"family":"Scharf","given":"Martin B."},{"family":"McDannold","given":"Michael D."},{"family":"Stover","given":"Robin"},{"family":"Zaretsky","given":"Nadia"},{"family":"Berkowitz","given":"David V."}],"issued":{"date-parts":[["1997",3,1]]}}}],"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"} (Scharf et al.).
Relief of urinary tract infections and sexual impairment
Due to the low level of estrogen at the vaginal site, Collagen loss occurs which increases the risk of urinary tract infections. The application of HRT usually minimizes the risk by the formation of new collagen. Moreover, the sexual problems faced as a result of low estrogen levels are also relieved ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"7SSdtuxs","properties":{"formattedCitation":"(Utian et al.)","plainCitation":"(Utian et al.)","noteIndex":0},"citationItems":[{"id":226,"uris":["http://zotero.org/users/local/CKNkWnK9/items/6AWPK966"],"uri":["http://zotero.org/users/local/CKNkWnK9/items/6AWPK966"],"itemData":{"id":226,"type":"article-journal","title":"Relief of vasomotor symptoms and vaginal atrophy with lower doses of conjugated equine estrogens and medroxyprogesterone acetate","container-title":"Fertility and Sterility","page":"1065-1079","volume":"75","issue":"6","source":"ScienceDirect","abstract":"Objective: To evaluate the efficacy of lower doses of conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA) for relieving vasomotor symptoms and vaginal atrophy. Design: A randomized, double-blind, placebo-controlled trial (the Women’s Health, Osteoporosis, Progestin, Estrogen study). Setting: Study centers across the United States. Patient(s): Two thousand, six hundred, seventy-three healthy, postmenopausal women with an intact uterus, including an efficacy-evaluable population (n = 241 at baseline). Intervention(s): Patients received for 1 year (13 cycles; in milligrams per day) CEE, 0.625; CEE, 0.625 and MPA, 2.5; CEE, 0.45; CEE, 0.45 and MPA, 2.5; CEE, 0.45 and MPA, 1.5; CEE, 0.3; CEE, 0.3 and MPA, 1.5; or placebo. Main Outcome Measure(s): Number and severity of hot flushes and Papanicolaou smear with vaginal maturation index (VMI) to assess vaginal atrophy. Result(s): In the efficacy-evaluable population, reduction in vasomotor symptoms was similar with CEE of 0.625 mg/d and MPA of 2.5 mg/d (the most commonly prescribed doses) and all lower combination doses. CEE of 0.625 mg/d alleviated hot flushes more effectively than the lower doses of CEE alone. VMI improved in all active treatment groups. Conclusion(s): Lower doses of CEE plus MPA relieve vasomotor symptoms and vaginal atrophy as effectively as commonly prescribed doses.","DOI":"10.1016/S0015-0282(01)01791-5","ISSN":"0015-0282","journalAbbreviation":"Fertility and Sterility","language":"en","author":[{"family":"Utian","given":"Wulf H"},{"family":"Shoupe","given":"Donna"},{"family":"Bachmann","given":"Gloria"},{"family":"Pinkerton","given":"Joanne V"},{"family":"Pickar","given":"James H"}],"issued":{"date-parts":[["2001",6,1]]}}}],"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"} (Utian et al.).
Relief of energy, sleep and mood impairment
Due to a high-level experience of hot flushes, menopausal women have reported having fatigue and depression. Lack of sleep due to the hot flushes makes women feel lazy and tired which in turn results in depression. According to the studies, HRT is thought to relieve these symptoms by directly decreasing the instance of hot flushes ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"oxPWMymY","properties":{"formattedCitation":"(Hlatky et al.)","plainCitation":"(Hlatky et al.)","noteIndex":0},"citationItems":[{"id":228,"uris":["http://zotero.org/users/local/CKNkWnK9/items/IL3GIFPC"],"uri":["http://zotero.org/users/local/CKNkWnK9/items/IL3GIFPC"],"itemData":{"id":228,"type":"article-journal","title":"Quality-of-Life and Depressive Symptoms in Postmenopausal Women After Receiving Hormone Therapy: Results From the Heart and Estrogen/Progestin Replacement Study (HERS) Trial","container-title":"JAMA","page":"591-597","volume":"287","issue":"5","source":"jamanetwork.com","abstract":"ContextPostmenopausal hormone therapy is commonly used by women for disease prevention, but its effects on quality of life have not been well documented.ObjectiveTo determine the effect on quality of life of estrogen plus progestin therapy used as secondary prevention in women with coronary artery disease.Design, Setting, and ParticipantsA total of 2763 postmenopausal women with documented coronary artery disease (mean age, 67 years) in the Heart and Estrogen/Progestin Replacement Study, a randomized, placebo-controlled, double-blind trial conducted from January 1993 to July 1998 at outpatient and community settings at 20 US clinical centers.InterventionParticipants were randomly assigned to receive either 0.625 mg/d of conjugated equine estrogen plus 2.5 mg/d of medroxyprogesterone acetate (n = 1380) or placebo (n = 1383) for 36 months.Main Outcome MeasuresPhysical activity, measured by the Duke Activity Status Index; energy/fatigue and mental health, measured by RAND scales; and depressive symptoms, measured on the Burnam screening scale, at 3 years of follow-up.ResultsIn all patients, scores declined significantly over 3 years for physical function (−3.8; P<.001), mental health (−0.6; P = .05), and energy/fatigue (−3.8; P<.001), but depressive symptoms were not significantly changed (P = .20). The effect of hormone therapy on these measures depended on the presence (n = 434) or absence (n = 2325) of flushing at study entry. Women with flushing who were assigned to hormone therapy had improved mental health (+2.6 vs − 0.5; P = .04) and fewer depressive symptoms (−0.5 vs + 0.007; P = .01) over follow-up compared with those assigned to placebo. Women without flushing who were assigned to hormone therapy had greater declines in physical function (−4.2 vs −3.3; P = .04) and energy/fatigue (−4.6 vs −3.1; P = .03) over follow-up. Quality-of-life scores were significantly lower among patients with older age, diabetes, hypertension, chest pain, or heart failure. These differences in quality of life among women classified by clinical characteristics were much greater than the effects of hormone therapy.ConclusionHormone therapy has mixed effects on quality of life among older women. The effects of hormone therapy depend on the presence of menopausal symptoms; women without flushing had greater declines in physical measures, while women with flushing had improvements in emotional measures of quality of life.","DOI":"10.1001/jama.287.5.591","ISSN":"0098-7484","title-short":"Quality-of-Life and Depressive Symptoms in Postmenopausal Women After Receiving Hormone Therapy","journalAbbreviation":"JAMA","language":"en","author":[{"family":"Hlatky","given":"Mark A."},{"family":"Boothroyd","given":"Derek"},{"family":"Vittinghoff","given":"Eric"},{"family":"Sharp","given":"Penny"},{"family":"Whooley","given":"Mary A."},{"family":"Group","given":"for the HERS Research"}],"issued":{"date-parts":[["2002",2,6]]}}}],"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"} (Hlatky et al.).
Skin repair and wound healing
The most common symptom of menopause is the thinning of skin due to the loss of collagen. This accelerates the aging process and increases the risk of injuries. Due to the thinning of the skin, it is more susceptible to skin disorders such as skin cancer. HRT has thought to improve the thickness of the skin because of collagen replenishment. This likewise increases the ability of the skin to heal and repair wounds ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"rpViH7gd","properties":{"formattedCitation":"(Warren and Halpert)","plainCitation":"(Warren and Halpert)","noteIndex":0},"citationItems":[{"id":220,"uris":["http://zotero.org/users/local/CKNkWnK9/items/9ESHRHTA"],"uri":["http://zotero.org/users/local/CKNkWnK9/items/9ESHRHTA"],"itemData":{"id":220,"type":"article-journal","title":"Hormone replacement therapy: controversies, pros and cons","container-title":"Best Practice & Research Clinical Endocrinology & Metabolism","page":"317-332","volume":"18","issue":"3","source":"DOI.org (Crossref)","DOI":"10.1016/j.beem.2004.02.005","ISSN":"1521690X","title-short":"Hormone replacement therapy","journalAbbreviation":"Best Practice & Research Clinical Endocrinology & Metabolism","language":"en","author":[{"family":"Warren","given":"Michelle P"},{"family":"Halpert","given":"Sari"}],"issued":{"date-parts":[["2004",9]]}}}],"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"} (Warren and Halpert).
Prevention of Osteoporosis
Due to the decreased production of ovarian hormones, women are at greater risk of osteoporosis and bone mineralization. This is due to the poor mineral absorption which subsequently results in decreased bone development. HRT reduces the risk of osteoporosis by providing enough levels of estrogen necessary for bone strength and function ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"8T9irUBH","properties":{"formattedCitation":"(Wells et al.)","plainCitation":"(Wells et al.)","noteIndex":0},"citationItems":[{"id":236,"uris":["http://zotero.org/users/local/CKNkWnK9/items/6W6B3IGY"],"uri":["http://zotero.org/users/local/CKNkWnK9/items/6W6B3IGY"],"itemData":{"id":236,"type":"article-journal","title":"V. Meta-Analysis of the Efficacy of Hormone Replacement Therapy in Treating and Preventing Osteoporosis in Postmenopausal Women","container-title":"Endocrine Reviews","page":"529-539","volume":"23","issue":"4","source":"academic.oup.com","abstract":"Objective: To review the effect of hormone replacement therapy (HRT) on bone density and fractures in postmenopausal women.","DOI":"10.1210/er.2001-5002","ISSN":"0163-769X","journalAbbreviation":"Endocr Rev","language":"en","author":[{"family":"Wells","given":"George"},{"family":"Tugwell","given":"Peter"},{"family":"Shea","given":"Beverley"},{"family":"Guyatt","given":"Gordon"},{"family":"Peterson","given":"Joan"},{"family":"Zytaruk","given":"Nicole"},{"family":"Robinson","given":"Vivian"},{"family":"Henry","given":"David"},{"family":"O’Connell","given":"Diane"},{"family":"Cranney","given":"Ann"}],"issued":{"date-parts":[["2002",8,1]]}}}],"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"} (Wells et al.).
Cons of a Hormonal Replacement Therapy
Increased risk of Breast cancer
As a conventional growth home, estrogen is thought to increase the risk of breast cancer. The increased levels of estrogen contribute to the unnecessary growth that develops into breast cancer. According to NHS, the incidence of breast cancer among women has accelerated in the five years of undergoing an HRT ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"CLsZsaNE","properties":{"formattedCitation":"(Chen et al.)","plainCitation":"(Chen et al.)","noteIndex":0},"citationItems":[{"id":239,"uris":["http://zotero.org/users/local/CKNkWnK9/items/24Q762SJ"],"uri":["http://zotero.org/users/local/CKNkWnK9/items/24Q762SJ"],"itemData":{"id":239,"type":"article-journal","title":"Hormone Replacement Therapy in Relation to Breast Cancer","container-title":"JAMA","page":"734-741","volume":"287","issue":"6","source":"jamanetwork.com","abstract":"ContextStudies of long-term hormone replacement therapy (HRT) suggest an associated increased risk of breast cancer, but whether this association differs according to histologic type of cancer has not been extensively studied.ObjectiveTo determine whether the association between HRT and risk of breast cancer varies by HRT formulation and differs across histologic cancer types.Design, Setting, and ParticipantsNested case-control study among 705 postmenopausal women enrolled in the Group Health Cooperative of Puget Sound (GHC) who were aged 50 to 74 years and had primary invasive breast cancer diagnosed between July 1, 1990, and December 31, 1995 (cases), and 692 randomly selected aged-matched female members of GHC (controls).Main Outcome MeasureIncidence and type of breast cancer by duration of HRT use in the 5-year period ending 1 year before diagnosis, which was ascertained from computerized pharmacy records.ResultsThe incidence of breast cancer, all histologic types combined, was increased by 60% to 85% in recent long-term users of HRT, whether estrogen alone or estrogen plus progestin. Longer use of HRT (odds ratio [OR], 3.07 for 57 months or more; 95% confidence interval [CI], 1.55-6.06) and current use of combination therapy (OR, 3.91; 95% CI, 2.05-7.44) were associated with increased risk of lobular breast cancer. Long-term HRT use was associated with a 50% increase in nonlobular cancer (OR, 1.52 for 57 months or more; 95% CI, 1.01-2.29).ConclusionOur data add to the growing body of evidence that recent long-term use of HRT is associated with an increased risk of breast cancer and that such use may be related particularly to lobular tumors.","DOI":"10.1001/jama.287.6.734","ISSN":"0098-7484","journalAbbreviation":"JAMA","language":"en","author":[{"family":"Chen","given":"Chi-Ling"},{"family":"Weiss","given":"Noel S."},{"family":"Newcomb","given":"Polly"},{"family":"Barlow","given":"William"},{"family":"White","given":"Emily"}],"issued":{"date-parts":[["2002",2,13]]}}}],"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"} (Chen et al.).
Increased risk of other cancers
HRT has proved as one of the risk factors for gynecological cancers such as ovarian cancer and endometrial cancer. This mainly occurs due to the increased levels of progesterone that contribute towards the unnecessary growth of tissues and cells ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"w101nokj","properties":{"formattedCitation":"(Coughlin et al.)","plainCitation":"(Coughlin et al.)","noteIndex":0},"citationItems":[{"id":242,"uris":["http://zotero.org/users/local/CKNkWnK9/items/DFFZS8A9"],"uri":["http://zotero.org/users/local/CKNkWnK9/items/DFFZS8A9"],"itemData":{"id":242,"type":"article-journal","title":"A meta-analysis of estrogen replacement therapy and risk of epithelial ovarian cancer","container-title":"Journal of Clinical Epidemiology","page":"367-375","volume":"53","issue":"4","source":"ScienceDirect","abstract":"Estrogen replacement therapy (ERT) has not been associated with epithelial ovarian cancer in most reported epidemiologic studies that have looked for an association. Some studies may have found weak statistically nonsignificant associations because the number of cases or number of women who reported estrogen use was small. We performed a meta-analysis of data from 15 case-control studies that provided data on ERT and risk of epithelial ovarian cancer. The 15 combined studies were statistically heterogeneous (χ2 (14) = 26.3, P < 0.05) in terms of the effect they found. When we combined these studies using a random effects model, we did not find a significant association of ERT with ovarian cancer (odds ratio = 1.1, 95% confidence interval = 0.9–1.3). There was no clear evidence of a dose–response relation with increasing duration of estrogen use in a subset of five studies that reported estrogen use by duration (overall slope = 0.0012, 95% confidence interval = −0.0055 to 0.0080). The influences of statistical outliers, study design (hospital or clinic controls vs. community controls), and location (U.S. and Canada vs. Europe and Australia) were examined. The odds ratio was 1.3 (95% confidence interval = 1.0–1.6) in the relatively homogeneous subset of four U.S. case-control studies with community controls, but we cannot rule out the possibility of uncontrolled confounding. The odds ratios for estrogen use for other subgroups defined by geographic location and type of control group were not significantly different from one.","DOI":"10.1016/S0895-4356(99)00179-1","ISSN":"0895-4356","journalAbbreviation":"Journal of Clinical Epidemiology","language":"en","author":[{"family":"Coughlin","given":"Steven S."},{"family":"Giustozzi","given":"AnnGene"},{"family":"Smith","given":"S. Jay"},{"family":"Lee","given":"Nancy C."}],"issued":{"date-parts":[["2000",4,1]]}}}],"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"} (Coughlin et al.).
Cardiovascular disorders
There are no clear studies who have contributed to the literature of associating the cardiovascular disease with HRT. However, it is believed that it could be the reason for increased stroke and cardiovascular disorders among women of above 60 age. In any case, HRT is not recommended as it has the potential of increasing the primary embolism ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"k7T3uZEv","properties":{"formattedCitation":"(Matthews et al.)","plainCitation":"(Matthews et al.)","noteIndex":0},"citationItems":[{"id":233,"uris":["http://zotero.org/users/local/CKNkWnK9/items/3LFEYTCG"],"uri":["http://zotero.org/users/local/CKNkWnK9/items/3LFEYTCG"],"itemData":{"id":233,"type":"article-journal","title":"Menopause and Risk Factors for Coronary Heart Disease","container-title":"New England Journal of Medicine","page":"641-646","volume":"321","issue":"10","source":"Taylor and Francis+NEJM","abstract":"POSTMENOPAUSAL women and women who have undergone oophorectomy have a higher risk of coronary artery disease than premenopausal women of similar ages.1 2 3 Smokers have an early natural menopause.4 A recent report suggests that when the confounding effects of smoking and age are considered, the increased risk of coronary artery disease associated with menopause may be restricted to women who have undergone bilateral oophorectomy and who have never received hormone-replacement therapy.5 Thus, whether or not an early natural menopause leads to an increase in the risk of coronary artery disease is unclear. On the other hand, studies of risk factors for . . .","DOI":"10.1056/NEJM198909073211004","ISSN":"0028-4793","note":"PMID: 2488072","author":[{"family":"Matthews","given":"Karen A."},{"family":"Meilahn","given":"Elaine"},{"family":"Kuller","given":"Lewis H."},{"family":"Kelsey","given":"Sheryl F."},{"family":"Caggiula","given":"Arlene W."},{"family":"Wing","given":"Rena R."}],"issued":{"date-parts":[["1989",9,7]]}}}],"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"} (Matthews et al.).
Works Cited
ADDIN ZOTERO_BIBL {"uncited":[],"omitted":[],"custom":[]} CSL_BIBLIOGRAPHY Chen, Chi-Ling, et al. “Hormone Replacement Therapy in Relation to Breast Cancer.” JAMA, vol. 287, no. 6, Feb. 2002, pp. 734–41. jamanetwork.com, doi:10.1001/jama.287.6.734.
Coughlin, Steven S., et al. “A Meta-Analysis of Estrogen Replacement Therapy and Risk of Epithelial Ovarian Cancer.” Journal of Clinical Epidemiology, vol. 53, no. 4, Apr. 2000, pp. 367–75. ScienceDirect, doi:10.1016/S0895-4356(99)00179-1.
Hlatky, Mark A., et al. “Quality-of-Life and Depressive Symptoms in Postmenopausal Women After Receiving Hormone Therapy: Results From the Heart and Estrogen/Progestin Replacement Study (HERS) Trial.” JAMA, vol. 287, no. 5, Feb. 2002, pp. 591–97. jamanetwork.com, doi:10.1001/jama.287.5.591.
Matthews, Karen A., et al. “Menopause and Risk Factors for Coronary Heart Disease.” New England Journal of Medicine, vol. 321, no. 10, Sept. 1989, pp. 641–46. Taylor and Francis+NEJM, doi:10.1056/NEJM198909073211004.
Scharf, Martin B., et al. “Effects of Estrogen Replacement Therapy on Rates of Cyclic Alternating Patterns and Hot-Flush Events during Sleep in Postmenopausal Women: A Pilot Study.” Clinical Therapeutics, vol. 19, no. 2, Mar. 1997, pp. 304–11. ScienceDirect, doi:10.1016/S0149-2918(97)80118-X.
Utian, Wulf H., et al. “Relief of Vasomotor Symptoms and Vaginal Atrophy with Lower Doses of Conjugated Equine Estrogens and Medroxyprogesterone Acetate.” Fertility and Sterility, vol. 75, no. 6, June 2001, pp. 1065–79. ScienceDirect, doi:10.1016/S0015-0282(01)01791-5.
Warren, Michelle P., and Sari Halpert. “Hormone Replacement Therapy: Controversies, Pros and Cons.” Best Practice & Research Clinical Endocrinology & Metabolism, vol. 18, no. 3, Sept. 2004, pp. 317–32. DOI.org (Crossref), doi:10.1016/j.beem.2004.02.005.
Wells, George, et al. “V. Meta-Analysis of the Efficacy of Hormone Replacement Therapy in Treating and Preventing Osteoporosis in Postmenopausal Women.” Endocrine Reviews, vol. 23, no. 4, Aug. 2002, pp. 529–39. academic.oup.com, doi:10.1210/er.2001-5002.
