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Clinical manifestations and diagnosis of primary ovarian insufficiency (premature ovarian failure)

Clinical manifestations and diagnosis of primary ovarian insufficiency (premature ovarian failure)
Literature review current through: Jan 2024.
This topic last updated: Nov 30, 2022.

INTRODUCTION — Primary ovarian insufficiency (POI) is defined as the development of hypergonadotropic hypogonadism before the age of 40 years [1]. The presenting symptoms are similar to those of menopause. In its fully developed form, it is associated with oligomenorrhea or amenorrhea, symptoms of estrogen deficiency, and gonadotropin levels in the menopausal range before age 40 years. POI is distinguished from "induced" POI, ie, POI that is due to early bilateral salpingo-oophorectomy (BSO) or gonadotoxic therapies (chemotherapy and radiotherapy). (See "Elective oophorectomy or ovarian conservation at the time of hysterectomy".)

The clinical manifestations and evaluation of women with POI (focusing on women with a normal karyotype) will be reviewed here. The pathogenesis, causes, and management of POI, overviews of autoimmune ovarian insufficiency and Turner syndrome, and the evaluation of diminished ovarian reserve in the setting of female infertility are all discussed separately. (See "Pathogenesis and causes of spontaneous primary ovarian insufficiency (premature ovarian failure)" and "Management of primary ovarian insufficiency (premature ovarian failure)" and "Autoimmune primary ovarian insufficiency (premature ovarian failure)" and "Clinical manifestations and diagnosis of Turner syndrome".)

DEFINITIONS AND EPIDEMIOLOGY — The age-specific incidence of POI is approximately 1 in 250 by age 35 years and 1 in 100 by age 40 years [2]. Natural menopause is defined as the permanent cessation of menstrual periods, determined retrospectively after a woman has experienced 12 months of amenorrhea without any other obvious pathological or physiological cause. It occurs at a median age of 51.4 years in normal women. Menopause is a reflection of complete, or near complete, ovarian follicular depletion, with resulting hypoestrogenemia and high follicle-stimulating hormone (FSH) concentrations. Menopause before age 40 years is considered to be abnormal and is referred to as primary ovarian insufficiency (POI). An alternative term, "premature ovarian insufficiency," is used by some experts. (See "Clinical manifestations and diagnosis of menopause".)

The terms "premature menopause" and "premature ovarian failure" were used in the past for POI, but both are inaccurate because many patients with POI intermittently produce estrogen and ovulate, a few experience intermittent return of regular menses, and, in 5 to 10 percent of cases, women conceive and have a normal pregnancy [3]. This can occur many years after the diagnosis [4].

POI is a spectrum disorder and is a continuum of impaired ovarian function. We define diminished ovarian reserve as impaired ovarian responsiveness to exogenous or endogenous gonadotropin stimulation despite the presence of regular and predictable ovulatory menstrual cycles. Overt POI refers to the presence of irregular menses, elevated serum gonadotropins, and reduced fertility (table 1).

Diminished ovarian reserve is not synonymous with POI. It is a term used in the context of female infertility evaluation and treatment. The term refers to women over age 40 years who also have abnormal ovarian reserve testing (including low serum anti-müllerian hormone levels), and/or a poor response to ovarian stimulation during in vitro fertilization. (See "Evaluation and management of infertility in females of advancing age", section on 'Diminished ovarian reserve'.)

CLINICAL FEATURES — Primary ovarian insufficiency (POI) is characterized by a change in menstrual function (oligomenorrhea and/or amenorrhea), elevated serum gonadotropins and low serum estradiol concentrations, and estrogen deficiency symptoms such as hot flashes and vaginal dryness. However, because intermittent ovarian function occurs in approximately 50 to 75 percent of women with POI [5-7], the absence of vasomotor symptoms or vaginal dryness should not dissuade one from considering the diagnosis of POI in a woman who presents with menstrual irregularity (table 1).

Change in menstrual cycles — Many women present because of irregular menstrual cycles; others may first present because of difficulty conceiving (table 1). Some may also present with primary amenorrhea.

Most women who develop 46,XX POI have experienced normal puberty and have established regular menses prior to the development of the condition [8]. A disturbance in menstrual pattern is the most common presenting symptom, but there is no characteristic menstrual history that heralds the onset of 46,XX POI [9]. Patients may develop amenorrhea acutely or experience a prolonged prodrome of oligomenorrhea.

POI sometimes first becomes apparent when menstruation fails to return after stopping oral contraceptives (OCs) or following a pregnancy. The OC in this instance has masked most of the characteristic features of POI, including the change in menstrual cycles, hot flashes, and increase in serum gonadotropins, so the individual is unaware that there is a problem until she stops the pill.

Consequences of estrogen deficiency — In the absence of exogenous estrogen replacement, women with POI are at an increased risk for a number of symptoms and comorbidities.

Hot flashes — In some women, vasomotor symptoms may begin before the development of abnormal menstrual cycles; they tend to occur just prior to menses when estrogen levels are lowest. In addition, some women taking OCs experience vasomotor symptoms during the placebo or pill-free part of the cycle [9]. (See "Menopausal hot flashes".)

Vaginal dryness — With progression to amenorrhea and profound estrogen deficiency, symptoms of atrophic vaginitis and dyspareunia eventually become prominent (if estrogen is not replaced). (See "Genitourinary syndrome of menopause (vulvovaginal atrophy): Clinical manifestations and diagnosis".)

Bone loss and osteoporosis — POI is an important risk factor for bone loss and osteoporosis [10-12], especially in young women who develop ovarian dysfunction before they achieve peak adult bone mass [13]. Women with POI also have a higher incidence of osteoporotic fractures [14] (see 'Assess bone mineral density with DXA' below). The approach to managing bone health in women with POI is reviewed separately. (See "Management of primary ovarian insufficiency (premature ovarian failure)", section on 'Importance of estrogen therapy'.)

In a large, cross-sectional study of young women with 46,XX POI as compared with control women, patients on average had 2 to 3 percent lower bone density in the lumbar spine, femoral neck, and total hip [15]. Approximately 50 percent of women with 46,XX POI had evidence of vitamin D deficiency as well as inadequate calcium intake, and 25 percent had no regular exercise program [15].

Cardiovascular morbidity and mortality — POI is associated with increased cardiovascular morbidity and mortality, possibly related to endothelial dysfunction [16-22]. (See "Overview of atherosclerotic cardiovascular risk factors in females", section on 'Early menopause' and "Overview of atherosclerotic cardiovascular risk factors in females", section on 'Other conditions associated with cardiovascular disease risk'.)

Observational data suggest that early menopause may be associated with small increases in total mortality and mortality due to ischemic heart disease [19,23-25] and also possibly ischemic stroke [26]. However, at this time, evidence is insufficient to recommend hormone replacement therapy for the sole purpose of preventing cardiovascular disease or stroke.

Other — Other potential consequences of estrogen deficiency include diminished sexual well-being [27-29].

Some studies suggest that women under age 43 years who undergo bilateral oophorectomy and do not receive estrogen replacement are at increased risk for dementia and cognitive decline [30]. This has also been demonstrated for women with POI [31]. (See "Elective oophorectomy or ovarian conservation at the time of hysterectomy", section on 'Cognitive function and neurologic disease'.)

Emotional health — The diagnosis of POI is emotionally traumatic for most women because it disrupts their life plans, hopes, and dreams with regard to raising a family. Women with POI may develop related depression and anxiety disorders [32,33]. Data suggest that depression frequently occurs after the onset of menstrual irregularity but often precedes the diagnosis of POI [34].

As compared with controls, women with 46,XX POI score adversely in the domains of physical and emotional health on the World Health Organization Quality of Life (WHOQOL)-BREF instrument [35].

In one report, women with 46,XX POI (n = 100) had higher scores on depression, anxiety, and negative affect scales when compared with a group of control women (n = 60) [36]. On regression analysis, factors that contributed significantly to these symptoms were illness uncertainty and stigma associated with the diagnosis. This diagnosis disrupts life plans and introduces symptoms of grief, anxiety, and depression. When the condition develops during adolescence, it is important to take a family systems approach to the evaluation [37,38].

Physical features — Most women with 46,XX POI have experienced normal pubertal development and menarche and have no abnormalities on physical examination, but occasionally, the following may be found:

Evidence of Hashimoto's thyroiditis or Graves' disease.

Increased skin pigmentation or vitiligo related to autoimmune primary adrenal insufficiency. In this case, orthostatic hypotension may also be present.

Signs of atrophic vaginitis may be seen, although normal vaginal examination including normal cervical mucus and vaginal maturation index may also be seen if there has been recent ovarian function [5,6,8].

Ovarian enlargement related to autoimmune lymphocytic oophoritis or a steroidogenic enzyme defect [39,40]. This may also be noted on pelvic ultrasound.

Ptosis, which has been associated with a rare familial form of POI (blepharophimosis/ptosis/epicanthus inversus syndrome [BPES]) [41]. (See "Pathogenesis and causes of spontaneous primary ovarian insufficiency (premature ovarian failure)", section on 'Other rare syndromic defects'.)

Features of Turner syndrome, which are reviewed in detail separately, include short stature, low posterior hairline, high arched palate, shield chest with widely spaced nipples, a wide carrying angle, and short fourth and fifth metacarpals. (See "Clinical manifestations and diagnosis of Turner syndrome".)

Biochemical features — The typical biochemical features of POI include low serum estradiol and elevated serum follicle-stimulating hormone (FSH) concentrations, similar to what is seen in normal menopause. However, as noted, many women have intermittent ovarian function, so normal laboratory findings may be seen in women who are having ovulatory menstrual cycles (table 1).

Transvaginal ultrasound — Antral follicles that appear to be endocrinologically active have been detected by transvaginal ultrasound examination in nearly 75 percent of women with 46,XX POI [5-7]. Autoimmune oophoritis may also be associated with the development of large, luteinized follicle cysts; the characteristic ultrasound appearance is enlarged cystic ovaries [39,40,42-46]. (See "Autoimmune primary ovarian insufficiency (premature ovarian failure)".)

DIAGNOSIS

Primary ovarian insufficiency — Primary ovarian insufficiency is a life-altering diagnosis. The diagnosis of primary ovarian insufficiency (POI) can be made definitively in women younger than 40 years with irregular menses in association with follicle-stimulating hormone (FSH) concentrations in the postmenopausal range (as defined by the measuring laboratory). The presence of amenorrhea is not required to make the diagnosis, as women frequently have intermittent ovarian function and spontaneous menses [5,6,8], even years after their initial presentation (algorithm 1 and table 1).

Measurement of serum FSH can be misleading in women with POI who still have intermittent ovarian function as it can be in the normal range during ovulatory cycles but in the postmenopausal range when experiencing oligo- or amenorrhea. If one suspects POI, we suggest measuring FSH on cycle day 3 in women with menstrual cycles; for women with amenorrhea, the sample can be drawn on a random day. If estradiol drawn on the same day is elevated >100 pg/mL, the FSH may be suppressed and indeterminate even in a patient with amenorrhea, owing to occasional follicle development that can occur.

The presence of hot flashes and/or vaginal dryness is suggestive of POI as these symptoms are uncommon in women with menstrual disturbances due to other causes. The absence of these symptoms does not rule out the possibility for the reasons mentioned above; many women have intermittent ovarian function with follicular development, estrogen secretion, and intermittently may have normal regular menses. (See 'Clinical features' above.)

The progestin-withdrawal test is no substitute for laboratory evaluation, because intermittent estradiol production can result in withdrawal bleeding but does not negate the diagnosis [8] (algorithm 1). (See "Evaluation and management of secondary amenorrhea", section on 'Assessment of estrogen status'.)

Diminished ovarian reserve — The evaluation of diminished ovarian reserve in the setting of infertility is reviewed in detail separately. In addition to day 3 FSH and estradiol measurements, measurement of serum anti-müllerian hormone concentration and antral follicle count (on transvaginal ultrasound) have been used. In most assays, an FSH measured on cycle day 3 that is >10 to 15 international units/L, with a simultaneous serum estradiol ≥80 pg/mL (294 pmol/L), is suggestive of lower fertility and diminished ovarian reserve POI (table 1). (See 'Definitions and epidemiology' above and "Female infertility: Evaluation", section on 'Assessment of ovarian reserve'.)

Importance of early diagnosis — Despite the fact that early diagnosis of POI is important for osteoporosis prevention (and possibly prevention of later coronary heart disease), many women experience a significant delay in diagnosis after the onset of a disordered menstrual pattern (as long as a five-year delay in 25 percent of women) [9]. In addition, over 50 percent of young women with POI have reported seeing three or more clinicians before laboratory testing was finally done [9].

Young women who experience menstrual irregularity for three or more consecutive months deserve evaluation at their first visit [47]. The presence of regular and predictable menstrual cycles is an indication that the hypothalamic-pituitary-ovarian axis is functioning properly. Loss of menstrual regularity may be a sign of ovarian insufficiency and the associated estrogen deficiency. (See "Evaluation and management of primary amenorrhea" and "Evaluation and management of secondary amenorrhea".)

Informing the patient of the diagnosis — The most important steps after making the diagnosis of primary ovarian insufficiency (POI) (algorithm 1) are to inform the patient of the diagnosis in a sensitive and caring manner, provide accurate information, and offer referral to appropriate resources for emotional support. This issue is reviewed in detail separately. (See "Management of primary ovarian insufficiency (premature ovarian failure)".)

EVALUATION TO EXCLUDE OTHER DISORDERS — Other tests that should be done to rule out other causes of menstrual cycle dysfunction include (algorithm 1) (see "Evaluation and management of secondary amenorrhea", section on 'Laboratory testing'):

A pregnancy test, which should be performed in any woman of childbearing age who has missed menses

Serum prolactin concentration, to determine if hyperprolactinemia is the cause of the symptoms

Thyroid-stimulating hormone (TSH) to determine whether thyroid disease is present, as thyroid disease can cause irregular menses and is more common in primary ovarian insufficiency (POI)

ADDITIONAL EVALUATION ONCE DIAGNOSIS IS MADE — Once the diagnosis of primary ovarian insufficiency (POI) is made, other evaluation should be performed to determine the underlying cause of the POI and to evaluate for the presence of coexisting disorders. The underlying cause has been considered to be unknown or "idiopathic" in up to 70 percent of women with POI. However, whole exome or whole genome sequencing studies have identified the cause of POI in approximately 30 to 35 percent of patients [48-50]. We do not suggest routine genetic testing at this time, although it is becoming more useful as the number of genes increases. (See 'Genetic testing' below.)

Our approach to evaluating patients is consistent with that of the American College of Obstetricians and Gynecologists [51].

Clues to underlying etiology — The medical history from a woman with possible POI may provide clues about the underlying etiology:

Prior ovarian surgery, chemotherapy, or radiation therapy, as these all may damage ovarian tissue.

Symptoms of anorexia, weight loss, vague abdominal pain, weakness, fatigue, salt craving, or increased skin pigmentation that suggest the presence of primary adrenal insufficiency. Approximately 3 percent of women with POI develop adrenal insufficiency, a 300-fold increase compared with the general population [52]. (See "Clinical manifestations of adrenal insufficiency in adults".)

A personal or family history of autoimmune diseases, either alone or in combination, that might suggest polyglandular autoimmune syndromes, such as hypothyroidism or Graves' disease, primary adrenal insufficiency, vitiligo, myasthenia gravis, hypoparathyroidism, recurrent mucocutaneous candidiasis, or type 1 diabetes. Celiac disease should also be considered. Autoimmune oophoritis may occur as part of type I or type II syndromes of polyglandular autoimmune syndrome. In one study of 457 women with POI, 15 percent had chronic lymphocytic thyroiditis, compared with a prevalence of 5.8 percent in the United States population of women [53]. (See "Causes of primary adrenal insufficiency (Addison disease)", section on 'Polyglandular autoimmune syndromes'.)

A family history of POI, because approximately 10 percent of cases are familial [54]. A family history of POI raises concern for a fragile X premutation.

A family history of fragile X syndrome, intellectual disability, developmental delay, Parkinsonism, intension tremor, ataxia, or dementia, because approximately 6 percent of cases of POI are associated with premutations in the fragile X messenger ribonucleoprotein 1 (FMR1) gene (the gene responsible for the fragile X syndrome and the fragile X-associated tremor/ataxia syndrome) [55,56]. (See "Pathogenesis and causes of spontaneous primary ovarian insufficiency (premature ovarian failure)", section on 'Fragile X syndrome premutation carriers' and 'Test for FMR1 premutation' below and "Fragile X syndrome: Prenatal screening and diagnosis".)

Association with deafness, because familial autosomal recessive POI may be associated with deafness as part of Perrault syndrome [57,58].

Test for adrenal autoantibodies — Young women with POI are at increased risk for developing autoimmune adrenal insufficiency, a potentially fatal disorder [59]. Generally, the development of disordered menses associated with POI precedes the development of symptomatic adrenal insufficiency by several years [60]. If proper screening is performed, approximately 3 percent of women with POI will be found to have asymptomatic autoimmune adrenal insufficiency [52,61].

As a screen for the presence of asymptomatic autoimmune adrenal insufficiency, serum adrenal cortical and 21-hydroxylase antibodies should be measured in all women at the time of diagnosis of 46,XX POI. Women with adrenal autoimmunity detected by the presence of autoantibodies have a 50 percent risk of developing adrenal insufficiency [62]. These women should then be evaluated for the presence of adrenal insufficiency by an 8 AM serum cortisol and plasma corticotropin (ACTH).

Testing for 21-hydroxylase antibodies may serve the dual purpose of screening for autoimmune adrenal insufficiency and making the diagnosis of autoimmune oophoritis. However, in rare cases, 21-hydroxylase antibodies may be negative despite a positive adrenal cortical test determined by indirect immunofluorescence (due to the presence of antibodies to other steroidogenic enzymes such as 17-hydroxylase or side-chain cleavage) [61].

Even if adrenal function is found to be normal at initial evaluation, women with positive adrenal cortical antibodies should be followed annually by these tests. Monitoring for women with negative antibodies is reviewed separately.

Further evaluation and management of these patients and the diagnosis of adrenal insufficiency are reviewed separately. (See "Autoimmune primary ovarian insufficiency (premature ovarian failure)" and "Determining the etiology of adrenal insufficiency in adults".)

Other autoimmune evaluation — Young women with POI are also at increased risk of autoimmune hypothyroidism and should be screened for this condition [63]. Testing should therefore include thyroid-stimulating hormone (TSH) and thyroid-peroxidase autoantibodies. Other disorders associated with autoimmune polyglandular syndrome are discussed elsewhere. (See "Causes of primary adrenal insufficiency (Addison disease)", section on 'Autoimmune adrenalitis' and "Diagnosis of and screening for hypothyroidism in nonpregnant adults", section on 'Thyroid peroxidase antibodies'.)

Ovarian biopsy to detect autoimmune oophoritis is not recommended [64]. (See "Autoimmune primary ovarian insufficiency (premature ovarian failure)", section on 'Diagnosis'.)

Karyotype — A karyotype should be performed as part of the basic evaluation for all patients with POI, with or without stigmata of Turner syndrome. Neither age of onset nor prior parity rules out a chromosomal abnormality. Overall, in patients who have experienced normal puberty before developing POI, an abnormal karyotype will explain the disorder in a low percentage of cases [8]. Women with X chromosome abnormalities have developed POI after having previously delivered normal children [65]. Identification of a chromosomal abnormality alters management, and thus, this test should be part of the standard evaluation. Women with Turner syndrome should be screened for associated abnormalities. (See "Clinical manifestations and diagnosis of Turner syndrome".)

Although rare in women with POI, those with Y chromosome material present require oophorectomy because of the risk of gonadal tumors in women with Y chromosome-containing gonadal tissue. Molecular genetic techniques to identify the critical Y chromosome components have been developed [66,67]. (See "Clinical manifestations and diagnosis of Turner syndrome", section on 'Risk of malignancy'.)

Test for FMR1 premutation — We agree with several professional organizations and suggest that women with overt and biochemical POI undergo testing for a premutation in FMR1 [68-70]. There is an established association between POI and premutation in the FMR1 gene, the gene responsible for fragile X syndrome [71]. Fragile X syndrome is an X-linked disorder that is the most common cause of heritable intellectual disability. (See "Fragile X syndrome: Clinical features and diagnosis in children and adolescents".)

In cases of familial POI, approximately 14 percent will be found to have a premutation in the FMR1 gene. In sporadic cases, the prevalence of this premutation is approximately 2 percent [72,73].

The FMR1 premutation as a mechanism of POI is associated with a clinical spectrum of impaired ovarian function (table 1). This involves a continuum from: diminished ovarian reserve as detected by a low response to gonadotropin stimulation in the context of infertility treatment, diminished ovarian reserve as detected by an elevated basal follicle-stimulating hormone (FSH) level (biochemical), and overt POI that is associated with disruption of the menstrual cycle [1,74,75].

Genetic testing — Up to 70 percent of women with POI have been considered to have idiopathic or "unexplained" POI. However, studies using whole exome or whole genome sequencing have identified genetic variants in approximately 30 to 35 percent of patients with POI [48]. In a prospective cohort study of 269 well-phenotyped women with POI screened for variants of 18 known POI genes by next-generation sequencing, 102 (38 percent) were identified as having at least one genetic abnormality [49]. Another study examining targeting 88 POI risk genes identified a genetic cause in 29 percent [50]. Given the increasing number of identified genetic variants in women with POI, routine genetic testing may soon be part of the clinical work-up.

Assess bone mineral density with DXA — POI is an important risk factor for bone loss and osteoporosis [10-12]. Therefore, at the time of diagnosis, a bone density test (dual-energy x-ray absorptiometry [DXA]) should be obtained. (See "Screening for osteoporosis in postmenopausal women and men" and "Overview of dual-energy x-ray absorptiometry".)

Women with POI have a higher incidence of osteoporotic fractures, largely because of estrogen deficiency [14]. The approach to managing bone health in women with POI is reviewed separately. (See "Management of primary ovarian insufficiency (premature ovarian failure)", section on 'Importance of estrogen therapy'.)

FOLLOW-UP AFTER DIAGNOSIS — There are many important issues to consider in the follow-up and management of women with a diagnosis of primary ovarian insufficiency (POI), including emotional health, fertility, sexual function, bone health, cardiovascular health, and the risk for developing primary adrenal insufficiency (in women with autoimmune oophoritis). Our approach is consistent with that of the American College of Obstetricians and Gynecologists [51]. All of these issues are reviewed separately. (See "Management of primary ovarian insufficiency (premature ovarian failure)".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Primary ovarian insufficiency".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Primary ovarian insufficiency (The Basics)")

Beyond the Basics topics (see "Patient education: Primary ovarian insufficiency (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Definition and epidemiology – Primary (or premature) ovarian insufficiency (POI, formerly referred to as premature ovarian failure) is one of many causes that may be found when evaluating a woman for amenorrhea or oligomenorrhea. The age-specific incidence of POI is approximately 1 in 250 by age 35 years and 1 in 100 by age 40 years. (See 'Introduction' above.)

Clinical features – POI is characterized by a change in menstrual function (oligomenorrhea and eventual amenorrhea), elevated serum gonadotropin and low serum estradiol concentrations, and estrogen deficiency symptoms such as hot flashes and vaginal dryness. However, because intermittent ovarian function occurs in approximately 50 to 75 percent of women with POI, the absence of vasomotor symptoms or vaginal dryness should not dissuade one from considering the diagnosis of POI in a woman who presents with menstrual irregularity (algorithm 1 and table 1). (See 'Clinical features' above.)

Diagnosis – The diagnosis of POI can be made definitively in women younger than 40 years with irregular menses in association with follicle-stimulating hormone (FSH) concentrations in the menopausal range levels, as defined by the testing laboratory (algorithm 1). The presence of amenorrhea is not required to make the diagnosis, as women frequently have intermittent ovarian function and spontaneous menses even years after their initial presentation. (See 'Diagnosis' above.)

The diagnosis of POI is emotionally traumatic for most women as it disrupts their life plans, hopes, and dreams with regard to fertility. Anxiety and/or depression are both common in women with POI. (See 'Emotional health' above.)

Diagnosis is important in order to explain to the patient the variable natural history of the condition, to look for associated diseases, and, most importantly, to treat the hypogonadism. (See 'Diagnosis' above.)

Additional evaluation – After the diagnosis of POI is made, other evaluation should be performed to determine the underlying cause of the POI and to evaluate for the presence of coexisting disorders. (See 'Additional evaluation once diagnosis is made' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Lawrence M Nelson, MD, who contributed to an earlier version of this topic review.

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Topic 7443 Version 26.0

References

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