2ier2018 Evaluation and management of secondary amenorthea - UpToDate UpToDate’ ores ton 62018 crebae In andoris alates. Anions Reeves. @)-Wolters Kluwer Evaluation and management of secondary amenorrhea, ‘thors: Corin K Well, MD, Robert L Bariar, MO Section Eators: Willan FCrowly. J MD, Michell E Gear, MD Deputy tor: Kathryn A Martin, MO [Alltop are updated as new evidence becomes avallable and our poor roviaw arocess Is complet. Literature review current through: Jan 2018. | This topic last updated: Doc 17, 2016 INTRODUCTION —Amenorthea (absence of menses) can be a transient, intermittent, or permanent condition resulting fram dysfunction af the hypothalamus, pituitary, ovaries, uterus, or vagina (lable 1 and able 2), Iis often classified as either primary (absence of menarche by age 15 years) or secondary {absence of menses for more than three months in gs or women who previously had regular menstrual cycles or six months in {rs oF women who had iregular menses (1). Missing a single menstrual period may not be important to assess, but amen lasting tre ‘months or more and oligomenorrhea (fewer than nine menstrual cycles per year or cycle length greater than 35 days) require investigation. The tlloiogic and diagnostic considerations for olgomenorthea are the same as for secondary amenorthea. ‘The evaluation of secondary amenorthea and a brief summary of reatment options are reviewed here. The epidemiology and causes of secondary amenorrhea and overviews of primary amenorrhea and abnormal uterine bleeding in adolescents are discussed separately. (See "Epidamiology and uses of secondary amenorrhea" and ‘Evaluation and management of prmary amenorrhea” and "Abnormal uterine bleeding in adolescents: Evaluation and approach to dagrosis") APPROACH TO EVALUATION — Once pregnancy has been ruled out, a logical approach to women with ether primary or secondary amenorrhea Is to consider disordars based upon the levels of control ofthe menstrual cyte: hypothalamus, pituitary, ovary, and uterus. Determining the site of the defect is important because i determines the appropriate therapeutic regimen, While the most common causes of secondary amenorrhea are likely to be functional hypothalamic amenorthea or polycystic ovary syndrome (PCOS), disorders with an anatomic or pathologic cause must be ruled out (algorithm 1) [2.3 Rule out pregnancy — A prognancy testis recommended as a frst step in evaluating any woman with secondary amenorrhea. Measurement of serum beta subunit of human chorionic gonadotropin (hCG) isthe most sensitive test. Commercially avalable home kis for measurement of hCG in Urine are improving, but the dlinician who suspects pregnancy should order a serum hCG measurement, even if the woman had a negative home test History — The woman should be asked about any past matical history, isk factors, or symploms that might suggest any ofthe major causs of secondary amenormiea or oligomenorrhea (algoitim 1 and table 4). The history should include the following questions: «Has there been stress, change in weight, diet, or exercise habs ors there an eating disorder or illness (that might result in functional hypothalamic amenorhea)? (See “Epidemiology and causes of secondary amenorrhea", sacton on Functional hyeathalamic amenorthea!) «Is the woman taking any drugs that might cause or be associated with amenortiea? The drug may be taken fora systemicillness that itself can cause hypothalamic amenorthea. Newly iitated or discontinued oral contracepives can be associated with several months of amenorrhea, as can androgenic drugs tke danazol ora high-dose progestin. Other drugs cause amenorrhea by increasing serum prolactin (PRL) concentrations, including metoclooramide and antipsychotic drugs. (See "Causes of hygerovolactinemia") Is there hirsutism, acne, and a history of regular menses (suggestive of hyperandrogenism)? (See “Clinical manifestations of palyeysic ovary ‘syndrome in adults") ‘= Ae thore symptoms of hypothalamic-ptutary disease, including headaches, visual eld defects, fatigue, or polyuria and polycipsia’ (See 1d evaluation of colar masses") ‘Ave there any symploms of estrogen deficiency, including hot lashes, vaginal dryness, poor sleep, or decreased libido? These symptoms may be prominent with primary ovaran insufficiency (PO)). In contrast, women with hypathalamic amenorrhea do net usually have these symptoms, 50 ng/ml (50 mogiL) a pituitary MRI should be performed unless a vary clear explanation is found for the elovaton (eg, untreated hypothyroidism or antipsychotic drug use). The goal of imaging isto evaluate the possibilty of @ hypothalamic or ptutary lesion. In the case of a lacotroph adenoma, the image wil allow determination of wether itis a microadenoma or a macroadenoma (st or >1 cm, respectively). (See "Clinical man festations and evaluation of hyperrolactnemia’ boralorylimasing test. High serum FSH concentration — A high serum folicle-stmulating hormane (FSH) concentration indicates POI, formerly referred to as premature ovarian fale, It should be kept in mine, however, that intermittent folicular development does occur in women with POI, resuting in transient normalization of serum FSH concentrations. During times of ovarian inacivly and amenorrhea, FSH is high and serum estradiol is ow, Similar to what is seen in normal menopause. The presence of hot lashes andlor vaginal dryness is suggestive of POI as these symptoms are Uncommon in women with menstrual disturbances due to other causes (algorithm 1). (See ‘Clinical manfestaions and dlagnos's of spontaneous primary ovarian insufciency (premature ovarian failure.) For patients without an obvious precipitating factor for POI (gonadatoxic chemotherapy or radiotherapy), additonal testing to rule out the most common etiologies of PO! should be performed, including a karyotype to look for Turner syndrome (Including mosaicism). In women with 45 XX spontaneous POI, we also suggest testing for antadrenal antibodies and the fragile X promutaton, (See "Clinical manfastatons and diagnosis of “Tumer syndrome”, section on ‘Diagnass' and “Pathogenesis and causes of spontaneous orimary ovarian insufficiency (aremature ovarian failure)” ‘and "Clinical manifestations and diagnosis of spontaneaus primary ovarian insufficiency (premature avaran failure.) Normal laboratory results and history of uterine instrumentation — Women with normal laboratory resuls and a history of uterine Instrumentation should be evaluated for intrauterine adhesions (Asherman syndrome). Many cniians stat witha progestin challenge (osaroxyprogesterone acetate 10 mg for 10 days) I withdrawal blesding occurs, an outiw tract disorder has been ruled out If bleeding does not accur, estragen and progestin may be administered. The endametium may be primed with oral conjugated estrogens 0.625 ‘malday or their equivalent (oral estradiol * mglday, transdermal estradiol 0.05 mg) for 35 days. A progestins then added from days 28 to 35 (typically medroxyprogesterone 10 mgiday). Failure o bleed upon cessation of tis therapy stzongly suggests endometrial scaring In this stuation, ‘8 hysterosslpingogram or direct visualization ofthe endometrial cavity with a hysteroscope can confrm the diagnosis a intrauterine adhesions (alganthm +). (See ‘Invautesine adnesions: Cinical manifestation and diagnosis") High serum andragen concentrations — Depending upon the cincal picture, a high serum androgen value may be consistent with the diagnosis of PCOS, or iit 's extremely high, it may raise the question of an andrager-secreting tumar af the avary or adrenal gland, Of note, many women with PCOS present with hyperandrogenism (acne, hirsutism) without hyperandrogenemia (algorthm 1). (See polycystic ovary syndrome in aduls" and "Diagnosis of polycystic avary syndrome in adults", section on ‘Diagnosis') linical manifestations of [Androgen-secreting tumors are typically associated withthe rapid onset of vrizing symptoms and, in some adrenal cases, with glucocorticoid ‘excess, Most clinicians inate evaluation for a tumar if the serum concentration of testosterone is greater than 150 to 200 ngid. (6.2 to 6.9 nmallL) or that of DHEAS is greater than 700 megidL (18.9 micromolL). This topic is discussed in detail separately (See valuation of premenopausal Abnormal TSH — Both hypo- and hyperthyroidism can be associated with oligo-or amenorthea. A third-generation tyroid-stimulating hormone (TSH) assay is usually all that is needed to diagnose hypo- or hyperthyroidism. The only exception would bein central hypothyroidism, where free thyroxine (T4) and TSH will both be low. In severe eating disorders, a suppressed TSH and free T4 may also be seen. In some cases of profound hypothyroidism, there may be a slight increase in serum PRI. (due to @ presumed increase in hypothalamic thyrotropin releasing hormone [TRH], which stimulates both TSH and PRL secretion) [3] (see ‘High serum prolactin concentration: above). Treatment ofthe hypothyroidism restores serum PRL to normal, Therefore, a pituitary MRI should not be performed unless hyperprolactinemia persis after the pation is euthyroid. MANAGEMENT Goals — The overall goals of management in women with secondary amenorthea include: + Conecting the underhing pathology, possible + Helping the woman ta achiove fet, desired + Proventing complications ofthe dsease process (eg, esvogen replacement to prevent osteoporosis) brief summary of treatment options is presented here. More detaled discussions are found separately Hypothalamic amenorrhea + Lifestyle changes — For many athletic women, explaining the need for adequate caloric intake to match energy expenditure sometimes results in incteased caloric intake or reduced exercise, fllawed by resumption of menses. However, many women are reluctant to moditytheit psa uptodate. comicontensfevaluaton-and-managementofsecondary-amenormealprit ano