Ob/Gyn - Amenorrhea

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1. Pregnancy 2. Anatomic abnormalities a. Congenital abnormality in Mullerian development* - Isolated defect - Androgen insensitivity syndrome - 5-Alpha-reductase deficiency - Vanishing testes syndrome - Defect in SRY gene b. Congenital defect of urogenital sinus development* - Agenesis of lower vagina - Imperforate hymen - Acquired ablation or scarring of endometrium - Asherman syndrome - Tuberculosis 3. Disorders of the hypothalamic-pituitary-ovarian axis - Hypothalamic dysfunction - Pituitary dysfunction - Ovarian dysfunction - Other

Causes classes

Pregnancy Anatomic abnormalities (Mullerian development/ urogenital sinus development) Disorders of the hypothalamic-pituitary-ovarian axis

Primary ovarian insufficiency

multiple heterogeneous causes lead to either ■follicle dysfunction where follicles remain in the ovary but pathological process prevents normal function ■follicle depletion where no primordial follicles remain in the ovary due to ■failure of adequate initial pool of follicles to be established in utero ■accelerated expenditure of follicles ■autoimmune, or toxic destruction of follicles

Definition

• Primary amenorrhea - absence of menarche ◦ aged ≥ 15 years with normal secondary sexual development ◦ aged ≥ 13 years with no secondary sexual characteristics • Secondary amenorrhea - cessation of regular menstruation after menarche ◦for 3 consecutive months in women with previously normal menstrual cycle (every 21-45 days) ◦for 6 consecutive months in women with previously irregular menstrual cycle

Functional hypothalamic amenorrhea

•energy deficiency is the critical factor in weight-loss- and exercise-induced forms •regardless of trigger, condition is characterized by ■suppression of gonadotropin-releasing hormone (GnRH) pulsatility ■overactivity of the hypothalamic-pituitary-adrenal axis ■underactivity of the hypothalamic-pituitary-thyroid axis ■estrogen deficiency

POS

•multifactorial endocrine disorder usually involving peripheral insulin resistance •amenorrhea is due to ovulatory dysfunction

Hyperprolactenemia

•prolactin synthesis and secretion by pituitary gland ■induced by estrogen, thyrotropin-releasing hormone, epidermal growth factor, and dopamine receptor antagonists ■suppressed by hypothalamic dopamine ■induces and maintains lactation of the breast •hyperprolactinemia results from interruption of hypothalamic-pituitary dopaminergic pathways by drugs, or pathological processes ■medications, including opiate, antidepressant, antihistamine, antihypertensive, and antipsychotic medications ■prolactin-secreting pituitary adenoma or other pituitary lesion; if suspected refer patient for magnetic resonance imaging of pituitary

Surgical treatments

•surgical intervention is required to treat certain causes of amenorrhea such as(2) ◦imperforate hymen, where a triangular shape of hymeneal tissue is removed ◦transverse vaginal septum, where the septum is excised to restore the vaginal anatomy •surgical creation of a neovagina, and if necessary excision of rudimentary uterus, may improve the quality of life of patient with Müllerian agenesis, but will not restore menstruation(2) •gonads should be removed in patients with Swyer syndrome (karyotype 46,XY, with gonadal failure) (2) ◦gonads do not secrete hormones ◦gonadal tumors may occur in up to 25% of patients •Asherman syndrome most often treated by hysteroscopic surgery ( Reprod Biol Endocrinol 2013 Dec 27;11:118 EBSCOhost Full Text ) •treatment of prolactinomas may include surgical resection (see hyperprolactinemia)(3)

Abnormal TSH

■ hyperthyroidism ■ hypothyroidism

Tests

◦ blood or urine test to exclude pregnancy (AAFP Grade C) ◦ consider pelvic ultrasound if gynecological examination not possible or insufficient, to establish presence or absence of uterus, ovaries, and any anatomic defect of the outflow tract ◦ measure serum hormone concentrations of • thyroid stimulating hormone (TSH) • prolactin • luteinizing hormone (LH) • follicle stimulating hormone (FSH) ■ elevated levels of LH and FSH suggest delayed puberty caused by defect in gonads ■ low or normal LH and FSH levels suggest constitutional delay of puberty, pituitary dysfunction, or hypothalamic disorder ◦ karyotype analysis in patients with primary amenorrhea and absent uterus, or gonadal dysgenesis to identify possible chromosomal cause of abnormalities ◦ magnetic resonance imaging to identify potential pituitary tumor in patients with amenorrhea and persistently elevated serum prolactin levels

Treatment

◦ female delayed puberty •watchful waiting is appropriate as pubertal development will occur spontaneously •short-term, low-dose estrogen treatment to induce pubertal development may be beneficial •consider counseling for patients with psychological difficulties and low self esteem due to short stature and immature physical status POS •for overweight women with polycystic ovary syndrome, weight loss combined with exercise is first-line treatment(2, 3) •treatment of anovulation may include ■hormonal contraceptives (such as oral contraceptives, patch, or vaginal ring) as first-line treatment of menstrual abnormalities ■metformin as second-line treatment of menstrual abnormalities ■insulin-sensitizing agents POI •hormonal therapy is mainstay of treatment with either hormone replacement therapy or the combined estrogen/progestogen contraceptive pill until average age of natural menopause •for women who do not desire children, effective contraception using non hormonal methods required Hyperprolactenemia •dopamine agonists are usual first-line treatment Surgery Functional hypothalamic syndrome •consider referral for multidisciplinary approach to treatment , including nutritional education and counseling, and psychological treatment with mental health practitioner •dietary treatment targets vary by individual but may include reversal of recent weight loss •Female Athlete Triad Coalition consensus statement recommendations include ■non-pharmacological therapy as mainstay of treatment for all athletes ■referral for treatment of low energy availability ■if non-pharmacological management unsuccessful, estrogen with cyclic progesterone

History findings

◦ galactorrhea, which may indicate hyperprolactinemia ◦ abnormal thyroid function ◦ characteristics of previous menses (if any) ◦ weight change (any cause) ◦ chronic illness ◦ abdominal pain, which may indicate ectopic pregnancy ◦ headache, vision changes, vomiting that may indicate prolactinoma ◦ androgen excess, such as hirsutism, acne, deepening of the voice, muscularization, and clitoromegaly ◦ vasomotor instability, that may indicate estrogen deficiency