Primary amenorrhea is defined as the failure to reach menarche.Evaluation should be undertaken if there is no pubertal development by 13 years of age, if menarche has not occurred five years after initial breast development, or if the patient is 15 years or older.12 In contrast, a normal menstrual cycle typically occurs every 21 to 35 days.2Primary amenorrhea is often, but not exclusively, the result of chromosomal irregularities that lead to primary ovarian insufficiency (e.g., Turner syndrome) or anatomic abnormalities (e.g., Müllerian agenesis).It is characterized by hyperandrogenism found on clinical or laboratory examination, polycystic ovaries as suggested by ultrasonography, and ovulatory dysfunction. Early effects of metformin in women with polycystic ovary syndrome: a prospective randomized, double-blind, placebo-controlled trial. Metformin-induced resumption of normal menses in 39 of 43 (91%) previously amenorrheic women with the polycystic ovary syndrome. The Rotterdam Consensus Criteria published in 2003 require the presence of two of the three above conditions for diagnosis, whereas the Androgen Excess Society's 2006 guidelines require hyperandrogenism and either of the remaining two conditions.41. Tan BK, Adya R, Chen J, Lehnert H, Sant Cassia LJ, Randeva HS. Genital examination may reveal virilization, evidence of an outflow tract obstruction, or a missing or malformed organ.
Treatment goals for patients with amenorrhea may vary considerably, and depend on the patient and the specific diagnosis. Each of these conditions is associated with varying clinical sequelae; thus, it is important to consider a broad differential diagnosis to avoid missing rare or emergent pathology.Zika virus and complications: Questions and answers, from the World Health Organization (Mar 2017)Zika, from the Center for Infectious Disease Research and Policy, Univeristy of Minnesota (Mar 2017)Infographic on DEET use from the Pediatric Environmental Health Speciality Unit (Nov 2016)Zika articles published in Obstetrics & Gynecology May 2016 - Volume 127 - Supplement 1 Abstracts of Papers and Posters to be Presented at the 64th Annual Clinical and Scientific Meeting of the American College of Obstetricians and Gynecologists, May 14-17, Washington, DC. Supplement sponsored by: Published May 2016 “Letzko Extraperitoneal Cesarean Section” (artist: F. If history or examination suggests a hyperandrogenic state, serum free and total testosterone and dehydroepiandrosterone sulfate concentrations are useful.14 If the patient is short in stature, a karyotype analysis should be performed to exclude Turner syndrome.115 If the presence of endogenous estradiol secretion is not evident from the physical examination (e.g., breast development), serum estradiol may be measured.7 A complete blood count and comprehensive metabolic panel may be useful if history or examination is suggestive of chronic disease.7Pelvic ultrasonography can help confirm the presence or absence of a uterus, and can identify structural abnormalities of reproductive tract organs.If a pituitary tumor is suspected, magnetic resonance imaging (MRI) may be indicated.8 Hormonal challenge (e.g., medroxyprogesterone acetate [Provera], 10 mg orally per day for seven to 10 days) with anticipation of a withdrawal bleed to confirm functional anatomy and adequate estrogenization, has traditionally been central to the evaluation.2 Some experts defer this testing because its correlation with estrogen status is relatively unreliable.1Müllerian agenesis, a condition characterized by a congenital malformation of the genital tract, may present with normal breast development without menarche, and may be associated with urinary tract defects and fused vertebrae.18 Other congenital abnormalities that may cause amenorrhea include imperforate hymen and transverse vaginal septum.In these conditions, products of menstruation accumulate behind the defect and can lead to cyclic or acute pelvic pain.Physical examination, as well as ultrasonography or MRI, is key to diagnosis, and surgical correction is usually warranted.18Rare causes of amenorrhea include complete androgen insensitivity syndrome, which is characterized by normal breast development, sparse or absent pubic and axillary hair, and a blind vaginal pouch; and 5-alpha reductase deficiency, which is characterized by partially virilized genitalia.1 In these conditions, serum testosterone levels will be in the same range as those found in males of the same age.19 The karyotype will be 46, XY, and testicular tissue should be removed to avoid malignant transformation.20A structural cause of secondary amenorrhea is Asherman syndrome: intrauterine synechiae caused by uterine instrumentation during gynecologic or obstetric procedures, which can be evaluated and treated with hysteroscopy.221Primary ovarian insufficiency, a condition characterized by follicle depletion or dysfunction leading to a continuum of impaired ovarian function, is suggested by a concentration of follicle-stimulating hormone in the menopausal range (per reference laboratory), confirmed on two occasions separated by one month, and diagnosed in patients younger than 40 years with amenorrhea or oligomenorrhea.6 Other terms, including premature ovarian failure, are used synonymously with primary ovarian insufficiency.69 Up to 1% of women may experience primary ovarian insufficiency.Most cases of secondary amenorrhea can be attributed to polycystic ovary syndrome, hypothalamic amenorrhea, hyperprolactinemia, or primary ovarian insufficiency. Initial workup of primary and secondary amenorrhea includes a pregnancy test and serum levels of luteinizing hormone, follicle-stimulating hormone, prolactin, and thyroid-stimulating hormone.Patients with primary ovarian insufficiency can maintain unpredictable ovarian function and should not be presumed infertile.Laboratory tests usually reveal low or low-normal levels of serum follicle-stimulating hormone, luteinizing hormone, and estradiol; however, these levels can fluctuate, and the clinical context is the discriminating factor.17 Patients with functional amenorrhea may demonstrate the features of the female athlete triad, which consists of insufficient caloric intake with or without an eating disorder, amenorrhea, and low bone density or osteoporosis.31 These patients should be screened for eating disorders, diets, and malabsorption syndromes (e.g., celiac disease).1Treatment of functional hypothalamic amenorrhea involves nutritional rehabilitation as well as reductions in stress and exercise levels.7 Menses typically return after correction of the underlying nutritional deficit.32 Bone loss is best treated by reversal of the underlying process, and the patient should undergo bone density evaluation and take calcium and vitamin D supplements.7 Although the bone loss is partly secondary to estrogen deficiency, estrogen replacement without nutritional rehabilitation does not reverse the bone loss. Metformin effects on clinical features, endocrine and metabolic profiles, and insulin sensitivity in polycystic ovary syndrome: a randomized, double-blind, placebo-controlled 6-month trial, followed by open, long-term clinical evaluation. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP.Combined OCs will restore menses, but will not correct bone density.7, pituitary adenoma, hypothyroidism, or mass lesion compromising normal hypothalamic inhibition.8 Elevated prolactin levels, whatever the cause, inhibit the secretion and effect of gonadotropins, and warrant MRI of the pituitary.8 Exceptions may occur in cases with a clear pharmacologic trigger and relatively low levels of serum prolactin (i.e., PCOS is a multifactorial endocrine disorder, usually involving peripheral insulin resistance. Glueck CJ, Wang P, Fontaine R, Tracy T, Sieve-Smith L. 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