Management of bone health in women with premature ovarian insufficiency: Systematic appraisal of clinical practice guidelines and algorithm development

Highlights

• Premature ovarian insufficiency (POI) is associated with an increased risk of osteoporosis.

• AGREE II evaluation indicates variable quality of clinical guidelines regarding bone health management in women with POI.

• There is a paucity of high-quality evidence to guide management.

• Hormone replacement therapy (unless contraindicated) at least until the age of usual menopause is recommended for POI.

Abstract

Background

Osteoporosis is a key concern of women with premature ovarian insufficiency (POI) but there are gaps in clinicians’ knowledge of bone health.

Objectives

1) To systematically evaluate the quality of clinical practice guidelines (CPGs) related to POI and bone health; 2) to formulate a management algorithm.

Methods

Systematic search for English-language clinical practice guidelines (CPGs) from August 2012 to August 2017 (PROSPERO registration number CRD42017075143). Four reviewers independently evaluated the methodological quality of included CPGs using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument (comprising 23 items across 6 domains) using the My AGREE PLUS platform. Inter-rater reliability was assessed using the intraclass correlation coefficient (ICC). Individual domain and total percentage scores were calculated for each CPG. Data from high-scoring CPGs were extracted and summarised to develop the algorithm, with subsequent refinement via expert and end-user clinician feedback.

Results

The systematic search yielded 16 CPGs for appraisal. ICC values were 0.71 (good) to 0.95 (very good). The quality of the CPGs was appraised as “high” in 4 cases, “average” in 8 and “low” in 4. High-quality CPGs had mean total scores of 82–96%. Recommendations from high-quality CPGs were summarised into 6 categories: screening; risk factors; initial assessment; diagnosis; subsequent assessment; and management. Only “management” had recommendations (moderate-quality to low-quality evidence) from all four high-quality CPGs. Limitations are reflected in the algorithm.

Conclusions

Most CPGs regarding bone health and POI are of average to poor quality. High-quality CPGs have evidence limitations and recommendation gaps indicating the need for further research.

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.