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Medicina
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Hormone Replacement Therapy: Benefits and Risks
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Hormone Replacement Therapy: Benefits and Risks

A special issue of Medicina (ISSN 1648-9144).

Deadline for manuscript submissions: closed (30 June 2019) | Viewed by 72260

Special Issue Editor

Dr. Maria Cristina Meriggiola

E-Mail Website
Guest Editor
Clinic of Gynecology and Physiopathology of Reproduction, Alma Mater Studiorum University of Bologna, Bologna, Italy
Interests: female and male hormonal contraception; cross-sex hormone replacement in transgender population; menopause: from physiology to hormonal and non-hormonal treatment

Special Issue Information

Dear Colleagues,

The global trend of increased life expectancy and the consequent increase in the number of women entering menopause has turned postmenopausal women’s health into a major public health issue. An increasing number of women will reach their 100th birthday, thus living half of their life post-menopause. Most aging-related diseases in women occur on average 10 years after the onset of menopause, and thus menopause represents an important opportunity to promote better health over the second half of women’s lives.

Clinical practice regarding the use of hormone treatment during menopause has undergone dramatic changes in the last decades. In the last century, hormones were widely and indiscriminately recommended for the treatment of menopausal women. In the early 2000s, the misinterpretation of influential studies abruptly changed the hormonal management of menopause, leaving many symptomatic women to “suffer in silence”, with no help to cope with the menopausal symptoms worsening the quality of their life. More recently, those studies have been criticized, reanalyzed and reinterpreted, and new molecules and formulations have been developed to favor a more personalized approach that better fulfils women’s individual needs. A re-evaluation of the whole balance of risks and benefits of menopause hormone treatment (MHT) suggests that benefits of the available treatments exceed the risks in healthy symptomatic postmenopausal women when MHT is initiated within 10 years of menopause or at the age of < 60 years.

With these aspects in mind and given their importance for women’s health, the journal Medicina is launching a Special Issue entitled “Menopause Hormone Treatment: Benefits and Risks”. It is our pleasure to invite you and your co-workers to submit review articles aimed at providing a comprehensive overview of the current understanding of the different aspects and risk/benefit ratio of MHT. The overall aim of this issue is to inform clinical practice and introduce the readers to the new era of MHT.

Dr. Maria Cristina Meriggiola
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Medicina is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • menopause
  • hormone
  • women’s health
  • cardiovascular disease
  • bone metabolism
  • sexual health

Published Papers (8 papers)

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Review

17 pages, 384 KiB  
Review
Cognition, Mood and Sleep in Menopausal Transition: The Role of Menopause Hormone Therapy
by Giulia Gava, Isabella Orsili, Stefania Alvisi, Ilaria Mancini, Renato Seracchioli and Maria Cristina Meriggiola
Medicina 2019, 55(10), 668; https://doi.org/10.3390/medicina55100668 - 01 Oct 2019
Cited by 64 | Viewed by 12606
Abstract
During the menopausal transition, which begins four to six years before cessation of menses, middle-aged women experience a progressive change in ovarian activity and a physiologic deterioration of hypothalamic-pituitary-ovarian axis function associated with fluctuating hormone levels. During this transition, women can suffer symptoms [...] Read more.
During the menopausal transition, which begins four to six years before cessation of menses, middle-aged women experience a progressive change in ovarian activity and a physiologic deterioration of hypothalamic-pituitary-ovarian axis function associated with fluctuating hormone levels. During this transition, women can suffer symptoms related to menopause (such as hot flushes, sleep disturbance, mood changes, memory complaints and vaginal dryness). Neurological symptoms such as sleep disturbance, “brain fog” and mood changes are a major complaint of women transitioning menopause, with a significant impact on their quality of life, productivity and physical health. In this paper, we consider the associations between menopausal stage and/or hormone levels and sleep problems, mood and reduced cognitive performance. The role of estrogen and menopause hormone therapy (MHT) in cognitive function, sleep and mood are also discussed. Full article
(This article belongs to the Special Issue Hormone Replacement Therapy: Benefits and Risks)
13 pages, 637 KiB  
Review
Vaginal Health in Menopausal Women
by Stefania Alvisi, Giulia Gava, Isabella Orsili, Giulia Giacomelli, Maurizio Baldassarre, Renato Seracchioli and Maria Cristina Meriggiola
Medicina 2019, 55(10), 615; https://doi.org/10.3390/medicina55100615 - 20 Sep 2019
Cited by 48 | Viewed by 7587
Abstract
The aim of this review is to provide an overview of genitourinary health in peri- and postmenopause, particularly of vulvovaginal atrophy (VVA), which is part of genitourinary syndrome (GSM). This condition has a high prevalence among post-menopausal women and negatively affects a woman’s [...] Read more.
The aim of this review is to provide an overview of genitourinary health in peri- and postmenopause, particularly of vulvovaginal atrophy (VVA), which is part of genitourinary syndrome (GSM). This condition has a high prevalence among post-menopausal women and negatively affects a woman’s quality of life. Epidemiology, signs, symptoms, diagnostic criteria of VVA and target treatments for restoring vaginal health are discussed in light of the most recent literature. Issues related to this condition in menopausal women are under-diagnosed, lack objective diagnostic criteria, and consequently under-treated. Over the years, many treatments have been developed but their long-term effectiveness and safety have yet to be clearly defined. Patients are often dissatisfied and stop treatment, suggesting the need for a more personalized and tailored approach to achieve better compliance and thereby effectiveness. The aim of this paper is to provide an overview of the most recent literature on VVA in order to help the gynecologist in the management of this condition. Full article
(This article belongs to the Special Issue Hormone Replacement Therapy: Benefits and Risks)
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11 pages, 302 KiB  
Review
The Controversial History of Hormone Replacement Therapy
by Angelo Cagnacci and Martina Venier
Medicina 2019, 55(9), 602; https://doi.org/10.3390/medicina55090602 - 18 Sep 2019
Cited by 103 | Viewed by 15383
Abstract
The history of hormone replacement therapy (HRT) started in the 1960s, with very high popularity in the 1990s. The first clinical trials on HRT and chronic postmenopausal conditions were started in the USA in the late 1990s. After the announcement of the first [...] Read more.
The history of hormone replacement therapy (HRT) started in the 1960s, with very high popularity in the 1990s. The first clinical trials on HRT and chronic postmenopausal conditions were started in the USA in the late 1990s. After the announcement of the first results of the Women’s Health Initiative (WHI) in 2002, which showed that HRT had more detrimental than beneficial effects, HRT use dropped. The negative results of the study received wide publicity, creating panic among some users and new guidance for doctors on prescribing HRT. The clear message from the media was that HRT had more risks than benefits for all women. In the following years, a reanalysis of the WHI trial was performed, and new studies showed that the use of HRT in younger women or in early postmenopausal women had a beneficial effect on the cardiovascular system, reducing coronary disease and all-cause mortality. Notwithstanding this, the public opinion on HRT has not changed yet, leading to important negative consequences for women’s health and quality of life. Full article
(This article belongs to the Special Issue Hormone Replacement Therapy: Benefits and Risks)
7 pages, 276 KiB  
Review
Current Evidence of the Oncological Benefit-Risk Profile of Hormone Replacement Therapy
by Marta D’Alonzo, Valentina Elisabetta Bounous, Michela Villa and Nicoletta Biglia
Medicina 2019, 55(9), 573; https://doi.org/10.3390/medicina55090573 - 07 Sep 2019
Cited by 42 | Viewed by 6383
Abstract
Hormone replacement therapy (HRT) remains the most effective treatment for menopausal symptoms and has been shown to prevent bone loss and fracture. The progestogen is added to provide endometrial protection in women with an intact uterus. After the publication of the initial WHI [...] Read more.
Hormone replacement therapy (HRT) remains the most effective treatment for menopausal symptoms and has been shown to prevent bone loss and fracture. The progestogen is added to provide endometrial protection in women with an intact uterus. After the publication of the initial WHI (Women’s Health Initiative) results in 2002 reporting an overall increased risk of breast cancer, many women discontinued HRT. Despite the re-analysis of the results by subgroups of patients and updates with extended follow-up, much controversy remains, which we will analyze later in the text. Different types of estrogen or progestogen, as well as different formulations, doses, and durations, may play a role in HRT’s effects on breast tissue. Evidence states that conjugated equine estrogen (CEE), compared to estro-progestin therapy, shows a better profile risk (HR 0.79, CI 0.65–0.97) and that, among different type of progestins, those structurally related to testosterone show a higher risk (RR 3.35, CI 1.07–10.4). Chronic unopposed endometrial exposure to estrogen increases the risk of endometrial hyperplasia and cancer, whereas the association with progestins, especially in continuous combined regimen, seems to reduce the risk (RR 0.71, CI 0.56–0.90). HRT was also associated with a protective effect on colon cancer risk (HR 0.61, CI 0.42–0.87). Data about ovarian and cervical cancer are still controversial. Full article
(This article belongs to the Special Issue Hormone Replacement Therapy: Benefits and Risks)
12 pages, 329 KiB  
Review
Cardiovascular Risk/Benefit Profile of MHT
by Paola Villa, Inbal Dona Amar, Maayan Shachor, Clelia Cipolla, Fabio Ingravalle and Giovanni Scambia
Medicina 2019, 55(9), 571; https://doi.org/10.3390/medicina55090571 - 06 Sep 2019
Cited by 8 | Viewed by 3465
Abstract
Background and Objectives: Data emerging from the Women’s Health Initiative (WHI) study point toward an association between menopausal hormone therapy (MHT) and cardiovascular (CV) risk. However, post hoc subgroup analyses stratifying participants according to their age and time since menopause, have opened the [...] Read more.
Background and Objectives: Data emerging from the Women’s Health Initiative (WHI) study point toward an association between menopausal hormone therapy (MHT) and cardiovascular (CV) risk. However, post hoc subgroup analyses stratifying participants according to their age and time since menopause, have opened the way to a better understanding of the relationship between estrogen and CV risk. The aim of this review was to revise the current literature and evaluate the CV risk or benefit following administration of MHT considering several factors such as MHT timing, dose, route of administration, and formulation. Materials and Methods: An electronic databases search of MEDLINE (PubMed), Cochrane Central Register of Controlled Trials, Web of Science, SCOPUS, congress abstracts, and Grey literature (Google Scholar; British Library) was performed, with the date range from each database’s inception until June 2019. All the studies evaluating MHT and cardiovascular risk, including thromboembolism or stroke, were selected. Results: Timing of MHT initiation was shown to be a critical factor in CV risk assessment. In concordance with the “timing hypothesis”, healthy symptomatic women who initiated MHT when aged younger than 60 years, or who were within 10 years of menopause onset, have demonstrated a reduction in both coronary heart disease (CHD) risk and all-cause mortality. In particular, MHT therapy was associated with improvement of subclinical signs of atherosclerosis. Venous thromboembolism (VTE) risk is reduced when low doses of oral estrogen are used. Moreover, transdermal hormonal application significantly reduces CV risk compared with oral administration. MHT impact on the CV system is influenced by either factors inherent to the specific regimen, or factors inherent to the specific patient. Hence, individualization of care is necessary. Conclusion: CV risk calculation should be considered by clinicians in order to exclude patients with high CV risk, in whom MHT is contraindicated. Assessing risks and benefits in a patient-centered approach according to individual’s features, health status, and personal preferences is important in order to realize a safe and effective treatment. Full article
(This article belongs to the Special Issue Hormone Replacement Therapy: Benefits and Risks)
18 pages, 572 KiB  
Review
Sexual Health in Menopause
by Irene Scavello, Elisa Maseroli, Vincenza Di Stasi and Linda Vignozzi
Medicina 2019, 55(9), 559; https://doi.org/10.3390/medicina55090559 - 02 Sep 2019
Cited by 70 | Viewed by 16565
Abstract
Sexual function worsens with advancing menopause status. The most frequently reported symptoms include low sexual desire (40–55%), poor lubrication (25–30%) and dyspareunia (12–45%), one of the complications of genitourinary syndrome of menopause (GSM). Declining levels of sex steroids (estrogens and androgens) play a [...] Read more.
Sexual function worsens with advancing menopause status. The most frequently reported symptoms include low sexual desire (40–55%), poor lubrication (25–30%) and dyspareunia (12–45%), one of the complications of genitourinary syndrome of menopause (GSM). Declining levels of sex steroids (estrogens and androgens) play a major role in the impairment of sexual response; however, psychological and relational changes related with aging and an increase in metabolic and cardiovascular comorbidities should also be taken into account. Although first-line therapeutic strategies for menopause-related sexual dysfunction aim at addressing modifiable factors, many hormonal and non-hormonal, local and systemic treatment options are currently available. Treatment should be individualized, taking into account the severity of symptoms, potential adverse effects and personal preferences. Full article
(This article belongs to the Special Issue Hormone Replacement Therapy: Benefits and Risks)
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17 pages, 887 KiB  
Review
The Impact of Hormonal Replacement Treatment in Postmenopausal Women with Uterine Fibroids: A State-of-the-Art Review of the Literature
by Elisa Moro, Eugenia Degli Esposti, Giulia Borghese, Federica Manzara, Margherita Zanello, Diego Raimondo, Giulia Gava, Alessandro Arena, Paolo Casadio, Maria Cristina Meriggiola and Renato Seracchioli
Medicina 2019, 55(9), 549; https://doi.org/10.3390/medicina55090549 - 30 Aug 2019
Cited by 13 | Viewed by 4592
Abstract
Background and Objectives: Hormonal replacement therapy (HRT) is effective in treating many debilitating symptoms of menopause. However, its use in women with uterine fibroids is widely debated, based on the susceptibility of these tumors to sexual steroids. This review aims to ascertain [...] Read more.
Background and Objectives: Hormonal replacement therapy (HRT) is effective in treating many debilitating symptoms of menopause. However, its use in women with uterine fibroids is widely debated, based on the susceptibility of these tumors to sexual steroids. This review aims to ascertain the effects of HRT on leiomyomas development and growth in postmenopausal women. Materials and Methods: Electronic databases (i.e., MEDLINE, Scopus, ClinicalTrials.gov, EMBASE, Sciencedirect, the Cochrane Library at the CENTRAL Register of Controlled Trials, Scielo) were searched from January 1990 until May 2019. All English-written studies evaluating the impact of various HRT regimens on uterine leiomyomas were selected. Results: Seventeen papers, considering a total of 1122 participants, were included. Fifteen of these were prospective trials, of which nine were randomized controlled trials. The remaining two works were a retrospective observational trial and a retrospective case series respectively. Five studies evaluated the effects of tibolone, also comparing it with various estrogen/progestin combinations, while two were about raloxifene. Thirteen studies compared different combinations of estrogens/progestins, the most common being transdermal estrogens (used in nine studies) and medroxyprogesterone acetate at different doses (used in 10 studies). Conclusions: For women with uterine fibroids, the choice of the most appropriate HRT regimen is crucial to avoid leiomyomas growth and the symptoms possibly related to it. Available data are conflicting, but suggest that uterine fibroids might be influenced by HRT, without representing an absolute contraindication to hormonal replacement therapy. Women with uterine fibroids subjected to HRT should be periodically examined and hormonal treatment should be discontinued if leiomyomas appear to increase in size. Moreover, the minimal effective dose of progestin should be employed. Full article
(This article belongs to the Special Issue Hormone Replacement Therapy: Benefits and Risks)
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Figure 1

9 pages, 316 KiB  
Review
Hormonal Replacement Therapy in Menopausal Women with History of Endometriosis: A Review of Literature
by Margherita Zanello, Giulia Borghese, Federica Manzara, Eugenia Degli Esposti, Elisa Moro, Diego Raimondo, Layla Omar Abdullahi, Alessandro Arena, Patrizia Terzano, Maria Cristina Meriggiola and Renato Seracchioli
Medicina 2019, 55(8), 477; https://doi.org/10.3390/medicina55080477 - 14 Aug 2019
Cited by 18 | Viewed by 4867
Abstract
Hormonal replacement therapy (HRT) is effective in treating the symptoms of menopause. Endometriosis is defined as the presence of functional endometrial tissue outside the uterine cavity with a tendency towards invasion and infiltration. Being an estrogen-dependent disease, it tends to regress after menopause. [...] Read more.
Hormonal replacement therapy (HRT) is effective in treating the symptoms of menopause. Endometriosis is defined as the presence of functional endometrial tissue outside the uterine cavity with a tendency towards invasion and infiltration. Being an estrogen-dependent disease, it tends to regress after menopause. Nevertheless, it affects up to 2.2% of postmenopausal women. Conclusive data are not available in the literature on the appropriateness of HRT in women with endometriosis or a past history of the disease. The hypothesis that exogenous estrogen stimulation could reactivate endometriotic foci has been proposed. The aim of this state-of-the-art review was to revise the current literature about endometriosis in perimenopause and menopause and to investigate the possible role of HRT in this setting of patients. An electronic databases search (MEDLINE, Scopus, ClinicalTrials.gov, EMBASE, Sciencedirect, the Cochrane Library at the CENTRAL Register of Controlled Trials, Scielo) was performed, with the date range of from each database’s inception until May 2019. All of the studies evaluating the impact of different HRT regimens in patients with a history of endometriosis were selected. 45 articles were found: one Cochrane systematic review, one systematic review, five narrative reviews, two clinical trials, two retrospective cohort studies, 34 case reports and case series. Some authors reported an increased risk of malignant transformation of endometriomas after menopause in patients assuming HRT with unopposed estrogen. Low-quality evidence suggests that HRT can be prescribed to symptomatic women with a history of endometriosis, especially in young patients with premature menopause. Continuous or cyclic combined preparations or tibolone are the best choices. HRT improves quality of life in symptomatic post-menopausal women, who should not be denied the replacement therapy only due to their history of endometriosis. Based on low-grade literature evidence, we recommend to prescribe combined HRT schemes; tibolone could be considered. Full article
(This article belongs to the Special Issue Hormone Replacement Therapy: Benefits and Risks)
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