Management of bone health in women with premature ovarian insufficiency: Systematic appraisal of clinical practice guidelines and algorithm development
Introduction
Premature Ovarian Insufficiency (POI) can be spontaneous or iatrogenic and is defined as loss of ovarian function with development of hypergonadotropic hypogonadism in women under the age of 40 years [1]. Spontaneous POI affects approximately 1% of women and is associated with genetic defects, autoimmune disorders, environmental factors and infections, but is most commonly idiopathic [2,3]. Iatrogenic POI can occur secondary to surgical intervention (E.g. bilateral oophorectomy), chemotherapy and/or radiotherapy [2,4].
The effects of oestrogen deficiency include menopausal symptoms such as: vasomotor symptoms, insomnia, mood lability, and vulvo-vaginal atrophy. Longer-term consequences of POI include an increased risk of cardiovascular disease and mortality, accelerated cognitive impairment, infertility and osteoporosis [2,[4], [5], [6]]. Women with POI have a significantly lower bone mineral density (BMD) [2,4,[7], [8], [9], [10], [11], [12], [13]] and a 1.5-fold greater risk of fracture compared to women who experience menopause at the typical age [[14], [15], [16]].
The estimated prevalence of osteoporosis in women with POI is approximately 8–14% [2,13]. Sex-steroids contribute to skeletal homeostasis during growth and adulthood. Bone loss starts after achieving peak bone mass regardless of changes in sex steroid concentrations but the sharp decline of oestrogen levels at menopause accelerates bone loss and leads to deterioration in bone microarchitecture [7,8].
Clinical practice guidelines (CPGs) are being increasingly used by clinicians to assist patient management [[17], [18], [19], [20]]. They encompass statements to aid clinicians’ decisions regarding appropriate care for specific clinical circumstances [17,18]. The benefits of using CPGs can include improved consistency of care and quality of clinical decisions by offering recommendations for clinicians who are uncertain how to proceed, updating outdated practices and providing reassurance about appropriateness of treatment based on authoritative recommendations [19]. Adherence to CPGs has been shown to improve the process of care as well as patient outcomes [20]. However, implementation of poor-quality guidelines may be detrimental to the patient and the health care system [17,18]. Many existing CPGs lack high-quality evidence and rigorous methodology, compromising their integrity [17,18,21].
Women with POI are cared for by a variety of clinicians whom are not necessarily specialists in bone health including primary care providers, gynecologists and endocrinologists. High-quality CPGs could be useful to simplify decision-making and provide more consistent care for these women. To date, there are numerous publications related to managing bone health in women with POI derived from varying sources, which are of unknown quality [1,2,[21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36]]. This may contribute to the observed variations in clinical practice and clinician knowledge gaps regarding management of POI, including bone health [37].
The aim of this study was to review the methodological quality of contemporary CPGs regarding bone health in women with POI and, using these findings, formulate a management algorithm to guide treating clinicians.
Section snippets
Methods
This systematic review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and was registered with The International Prospective Register Of Systematic Reviews (PROSPERO) (Registration number CRD42017075143). A systematic review was conducted of contemporary CPGs in which management of bone health in POI was addressed.
Results
Our search identified 145 records, 16 of which met our inclusion criteria (Fig. 1) and characteristics of included CPGs are presented in Table 1.
Discussion
Our systematic search and AGREE II appraisal of CPGs related to POI and bone health indicates variability in quality domains between guidelines. Of the 16 CPGs evaluated, only four were assessed as high-quality and recommended by reviewers. Analysis of CPG content revealed variability and a paucity of high-quality evidence to guide management. Despite these limitations, a management algorithm to assist clinicians in the management of bone health in POI was developed and refined.
The finding of
Conclusion
Most CPGs regarding bone health in women with POI are of average to poor-quality with significant limitations in most AGREE II domains. The AGREE II instrument could assist CPG development to optimize quality and also when deciding which CPGs to implement in clinical practice. The limited evidence underpinning recommendations indicates the need for further research. From the available evidence and with stakeholder engagement, we have devised a management algorithm to aid clinicians in the
Contributors
Velislava Kiriakova participated in the data analysis and interpretation, and the drafting and revision of the manuscript.
Shamil D Cooray participated in the study design, data acquisition and analysis, and the drafting and revision of the manuscript.
Ladan Yeganeh participated in the data analysis, and the drafting and revision of the manuscript.
Gowri Somarajah participated in data acquisition and revision of the manuscript.
Frances Milat participated in all aspects of preparation of the
Funding
This work was supported by Osteoporosis Australia-ANZBMS 2016 grant awarded to AJ Vincent.
Ethical statement
This study did not involve experimentation with human subjects and therefore informed consent and ethical approval was not required.
Provenance and peer review
This article has undergone peer review.
Research data (data sharing and collaboration)
There are no linked research data sets for this paper. Data will be made available on request.
Declaration of Competing Interest
Amanda J Vincent serves on the editorial board of the journal Climacteric, which published one of the clinical practice guidelines in the study.
All other authors declare that they have no conflict of interest.
Acknowledgements
The authors would like to thank the clinicians who provided feedback regarding the draft algorithm.
This study was presented as a poster presentation at the Endocrine Society of Australia 2018 Annual Scientific Meeting, Adelaide.
References (55)
- et al.
Primary ovarian insufficiency
Lancet
(2010) - et al.
Bone loss in young women with karyotypically normal spontaneous premature ovarian failure
Obstet. Gynecol.
(1998) - et al.
Effect of clinical guidelines on medical practice: a systematic review of rigorous evaluations
Lancet
(1993) - et al.
EMAS position statement: the ten point guide to the integral management of menopausal health
Maturitas
(2015) - et al.
The European Society of Breast Cancer specialists recommendations for the management of young women with breast cancer
Eur. J. Cancer
(2012) - et al.
Spanish consensus on premature menopause
Maturitas
(2015) - et al.
First international consensus guidelines for breast cancer in young women (BCY1)
Breast
(2014) - et al.
Managing menopause
J. Obstet. Gynaecol. Can.
(2014) - et al.
Systematic review of current guideline appraisals performed with the Appraisal of Guidelines for Research & Evaluation II instrument—a third of AGREE II users apply a cut-off for guideline quality
J. Clin. Epidemiol.
(2018) Management of Women with Premature Ovarian Insufficiency
(2015)
Premature ovarian insufficiency in general practice: meeting the needs of women
Aust. Fam. Phys.
Incidence of premature ovarian failure
Obstet. Gynecol.
Postmenopausal status and early menopause as independent risk factors for cardiovascular disease: a meta-analysis
Menopause
Impaired endothelial function in young women with premature ovarian failure: normalization with hormone therapy
J. Clin. Endocrinol. Metab.
The role of estrogen and androgen receptors in bone health and disease
Nat. Rev. Endocrinol.
Osteoporosis in young adults: pathophysiology, diagnosis, and management
Osteoporos. Int.
Bone mineral density in estrogen-deficient young women
J. Clin. Endocrinol. Metab.
Bone mineral density in young women with primary ovarian insufficiency: results of a three-year randomized controlled trial of physiological transdermal estradiol and testosterone replacement
J. Clin. Endocrinol. Metab.
Bone loss in young women with premature ovarian failure
Arch. Gynecol. Obstet.
Phenotyping and genetic studies of 357 consecutive patients presenting with premature ovarian failure
Eur. J. Endocrinol.
Early menopause: increased fracture risk at older age
Osteoporos. Int.
Early menopause and risk of osteoporosis, fracture and mortality: a 34-year prospective observational study in 390 women
BJOG Int. J. Obstet. Gynaecol.
Effect of early menopause on bone mineral density and fractures
Menopause
Systematic evaluation of the quality of clinical practice guidelines on the use of assisted reproductive techniques
Hum. Fertil.
Clinical guidelines: potential benefits, limitations, and harms of clinical guidelines
BMJ
Critical evaluation of the scientific content in clinical practice guidelines
Cancer
Cited by (14)
Bone and heart health in menopause
2022, Best Practice and Research: Clinical Obstetrics and GynaecologyCitation Excerpt :National and international guidelines for the management of POI are available from the British Menopause Society (BMS) [17], European Society of Human Reproduction and Embryology (ESHRE) [18], International Menopause Society (IMS) [19], and the National Institute for Healthcare Excellence (NICE) [20]. A systematic appraisal of clinical guidelines [21] for bone health in women with POI found that most clinical practice guidelines for bone health in POI are of average to poor quality, with limited evidence to support recommendations. BMS [17], ESHRE [18], and IMS [19] guidelines recommend screening for low BMD with DEXA scan at baseline and again within 5 years of diagnosis, particularly if BMD was low at the initiation of hormone therapy (HT).
Postmenopausal hormone replacement therapy: a practical guide!
2023, Austrian Journal of Clinical Endocrinology and MetabolismFemale reproductive health in pediatric, adolescent, and young adult cancer survivors
2023, Pediatric Blood and CancerSecondary Osteoporosis
2022, Endocrine Reviews
- 1
Equal senior authors.
- 2
Postal address for all authors: Monash Centre for Health Research and Implementation, 43-51 Kanooka Grove, Clayton, 3168, Victoria, Australia.