Current Concepts in Premature Ovarian Insufficiency

Abstract

Premature ovarian insufficiency (POI) is a life-changing diagnosis, with profound physical and psychological consequences. Unfortunately, there are many deficiencies in our understanding of the condition as the underlying etiology and optimum management strategies are poorly understood. Improved awareness of POI and its long-term implications has led to increased research interest in recent years. Current research has allowed a greater understanding of the changing epidemiology in POI, genetic factors in its etiology and randomized controlled trials of hormone therapy are underway to provide evidence for treatment. This article reviews the latest literature on POI to summarize current understanding and future directions. Premature ovarian insufficiency (POI) is a life-changing diagnosis, with profound physical and psychological consequences, affecting approximately one in 100 women by the age of 40 years [1]. Unfortunately, there are many deficiencies in our understanding of the condition as the underlying etiology and optimum management strategies are poorly understood. Furthermore, controversy exists surrounding the terminology and diagnostic criteria, all of which can have a significant impact on the patients' well-being.Improved awareness of POI and its longterm implications has led to increased research interest in recent years. Current research has allowed a greater understanding of the changing epidemiology in POI, genetic factors in its etiology and randomized controlled trials (RCTs) of hormone therapy (HT) are underway to provide evidence for treatment. Here we aim to review the latest literature on POI to summarize current understanding and future directions. TerminologyThere has been a long-standing lack of consensus over the nomenclature of the disorder, with a variety of other terms in use, such as primary ovarian insufficiency, premature ovarian failure, premature menopause and hypergonadotrophic hypogonadism. We use the term premature ovarian insufficiency as it encompasses both spontaneous POI and the increasing number of women who have suffered POI as a result of iatrogenic interventions. The term insufficiency, rather than failure, is thought to more accurately reflect the unpredictable nature of ovarian function in the disorder as intermittent ovarian function, resulting in ovulation and even pregnancy, can occur [2,3]. The use of the term 'premature' refers to the timeline rather than the etiology, that is, ovarian insufficiency which has occurred before 40 years of age from any cause. It is important to note, however, that the condition does not always develop by the same mechanism as the normal menopause, which is due to follicle depletion. For example, some women develop POI due to mutations in the follicle stimulating hormone (FSH) receptor -these women have follicles in the ovary that are unable to function. Another example is steroidogenic cell POI has traditionally been defined as the triad of amenorrhea, elevated gonadotrophins and estrogen deficiency occurring in women under the age...

Occult form of premature ovarian insufficiency

“…The condition differs from menopause in that there are varying and residual ovarian functions [2,3]. According to the new ESHRE guidelines, POI is a clinical syndrome defined by the loss of ovarian activity in a woman before the age of 40 [4].…”

“…In these cases, the earliest ovarian reserve assessment is very important. Well-known parameters of ovarian reserve are: a woman's age, antral follicle count determined by pelvic ultrasound on days 4-8, day 3 FSH and estradiol, AMH and Inhibin B serum levels [1,2]. However, serum FSH and estradiol levels may fluctuate and could not be markers of precise ovarian reserve assessment in the occult form of POI.…”

Best practice for HRT: unpicking the evidence

“…11 We all should have a lower threshold for asking women when their last period was and then acting appropriately.…”

Premature Ovarian Failure of Autoimmune Causes

“…The best example for this is the premature ovarian failure (POF) of autoimmune causes. Generally POF (or premature ovarian insufficiency) represents the clinical end stage of ovarian function in women less than 40 years old [1][2][3][4] . The estrogens are low and the Follicle Stimulant Hormone (FSH) is high (above 40 mIU/mL) while the clinical main feature is the absence of menses for several months and hypoestrogenic state associated symptoms [2][3][4] .…”

“…Generally POF (or premature ovarian insufficiency) represents the clinical end stage of ovarian function in women less than 40 years old [1][2][3][4] . The estrogens are low and the Follicle Stimulant Hormone (FSH) is high (above 40 mIU/mL) while the clinical main feature is the absence of menses for several months and hypoestrogenic state associated symptoms [2][3][4] . The decreased number of ovarian follicles or follicular dysfunction are the pathogenic backgrounds for the condition [1][2][3][4] .…”