Medication Summary
Medical therapy of anovulation should be directed at reversal of the primary underlying cause and tailored to the individual patient.
Ovulation stimulators
Class Summary
Used for ovulation induction.
Clomiphene citrate (Serophene, Clomid, Milophene)
Stimulates release of pituitary gonadotropins. Acts as an antiestrogen to decrease negative estrogen feedback on hypothalamus. In addition, may have effects on pituitary gland and ovaries and can induce ovulation in women with hypothalamic amenorrhea. Improves folliculogenesis and, therefore, ovarian function during luteal phase.
Thyroid products
Class Summary
Used to correct hypothyroidism.
Levothyroxine (Synthroid, Levoxyl, Levothroid)
If luteal phase dysfunction is caused by hypothyroidism, correction of endocrine disease results in normal luteal phase.
Oral contraceptives
Class Summary
Used for hormone replacement.
Norethindrone/ethinylestradiol (Ortho-Novum, Ovcon 35, Ovcon 50)
In young females, low-dose PO contraception generally is an excellent method of hormone replacement. Any low-dose combination pill with 35 mcg of ethinyl estradiol or less or any progestin is appropriate. Also useful because, on occasion, these women may spontaneously ovulate and become pregnant.
Norgestimate/ethinyl estradiol (Ortho-Prefest, Ortho TriCyclen, Ortho-Cyclen)
In young females, low-dose PO contraception generally is an excellent method of hormone replacement. Any low-dose combination pill with 35 mcg of ethinyl estradiol or less or any progestin is appropriate. Also useful because, on occasion, these women may spontaneously ovulate and become pregnant.
Bisphosphonate derivatives
Class Summary
Analogs of pyrophosphate and act by binding to hydroxyapatite in bone matrix, thereby inhibiting dissolution of crystals. Prevent osteoclast attachment to the bone matrix and osteoclast recruitment and viability.
Alendronate (Fosamax)
Inhibits bone resorption via actions on osteoclasts or osteoclast precursors. Used to treat osteoporosis in both men and women. May reduce bone resorption and incidence of fracture at spine, hip, and wrist by approximately 50%. Should be taken with a large glass of water at least 30 min before eating and drinking to maximize absorption. Because of possible esophageal irritation, patients must remain upright after taking the medication. Since it is renally excreted, not recommended in patients with moderate-to-severe renal insufficiency (ie, CrCl < 30 mL/min or serum Cr > 3 mg/dL); use in perirenal transplantation is limited.
Oral antidiabetic agents
Class Summary
May increase glucose uptake in peripheral tissues.
Metformin (Glucophage)
Reduces hepatic glucose output, decreases intestinal absorption of glucose, and increases glucose uptake in the peripheral tissues (muscle and adipocytes). Major drug used in obese patients who have type 2 diabetes mellitus.
Antiandrogens
Class Summary
May inhibit androgen feedback on pituitary gland.
Finasteride (Proscar, Propecia)
Blocks conversion of testosterone to its more active metabolite, dihydrotestosterone. More effective when used in combination with OCPs.
Spironolactone (Aldactone)
Aldosterone antagonist that inhibits ovarian and adrenal production of androgens. Competes with dihydrotestosterone binding at hormone receptor sites on hair follicle cells. Also reduces 17alpha-hydroxylase activity, lowering plasma levels of testosterone and androstenedione.
Glucocorticoids
Class Summary
May be used to correct adrenal insufficiency.
Fludrocortisone (Florinef)
Partial replacement therapy for primary and secondary adrenocortical insufficiency.
Antifungal agents
Class Summary
Inhibit a variety of cytochrome P-450 enzymes, including 11beta-hydroxylase and 17-alpha-hydroxylase, which in turn, inhibit steroid synthesis.
Ketoconazole (Nizoral)
Inhibits steroid synthesis at the level of 17-alpha-hydroxylase/17,20-lyase, a key enzyme in sex steroid production. Also inhibits testosterone binding to its binding globulin. In some cases, especially in children with markedly advanced bone age, a rapid decrease in sex hormone levels may trigger true central puberty. In this event, add GnRH analogs to the treatment regimen.
Dopamine agonists
Class Summary
Directly stimulate postsynaptic dopamine receptors. The dopaminergic neurons in the tuberoinfundibular process modulate the secretion of prolactin from the anterior pituitary by secreting a prolactin inhibitory factor (believed to be dopamine).
Pergolide was withdrawn from the US market March 29, 2007, because of heart valve damage resulting in cardiac valve regurgitation. It is important not to abruptly stop pergolide. Health care professionals should assess patients' need for dopamine agonist (DA) therapy and consider alternative treatment. If continued treatment with a DA is needed, another DA should be substituted for pergolide. For more information, see FDA MedWatch Product Safety Alert and Medscape Alerts: Pergolide Withdrawn From US Market.
Pergolide (Permax)
Pergolide withdrawn from US market. Inhibits secretion of prolactin (PRL); causes a transient rise in serum concentrations of GH and decreases serum concentrations of LH.
Progestins
Class Summary
May be used for endometrial stabilization and organization of basal layer in chronic anovulation.
Medroxyprogesterone acetate (Provera, Cycrin, Depo-Provera)
Derivative of progesterone. Androgenic and anabolic effects have been noted, but apparently is devoid of significant estrogenic activity. Parenterally administered dosage form inhibits gonadotropin production, which in turn, prevents follicular maturation and ovulation. Available data indicate that this does not occur when the usually recommended PO dose is administered qd. When orally administered in the recommended doses to women adequately exposed to exogenous or endogenous estrogen, transforms the proliferative endometrium into a secretory one.
Estrogens
Class Summary
May be used to build endometrial lining in acute and chronic anovulation.
Estrogens, conjugated/equine (Premarin)
May be used for restoration of regular menstrual cycles, which may prevent endometrial hyperplasia associated with anovulation. Improvements of hyperandrogenic effects occur in 60-100% of women but usually require a minimum of 6-12 mo of use. A pregnancy test should be performed before initiating therapy. If the woman has had no menstrual period for 3 mo, withdrawal bleeding should be induced by administration of 5-10 mg of medroxyprogesterone acetate (Provera) qd for 10 d; therapy is then begun with OCPs.
Nonsteroidal anti-inflammatory drugs
Class Summary
Reduce blood loss by 30-50% in cases of anovulatory bleeding.
Ibuprofen (Advil, Motrin, Excedrin IB)
Used for reduction in uterine bleeding and dysmenorrhea associated with anovulatory cycles. Blocks formation of prostacyclin, an antagonist of thromboxane, a substance that accelerates platelet aggregation and initiates coagulation. Because NSAIDs inhibit blood prostacyclin formation, they might effectively decrease uterine blood flow.
Aromatase inhibitors
Class Summary
These agents inhibit aromatase activity, which causes serum estrogen levels to reduce.
Letrozole (Femara)
Reduces circulating estrogen inhibiting the estrogen negative feedback of the HPA. Results in increased secretion of FSH and thus ovarian follicle development.
Anastrozole (Arimidex)
Aromatase inhibitor that significantly lowers serum estradiol concentrations by inhibiting the conversion of adrenally generated androstenedione to estrone. Used as first-line treatment of breast cancer in postmenopausal women with hormone receptor positive or hormone receptor unknown locally advanced or metastatic disease. Also used to treat advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy.
Gonadotropins
Class Summary
These agents stimulate ovarian follicular growth.
Follitropin alfa (Gonal-F)
Exogenous FSH stimulates proliferation of granulosa cells and follicular growth. Release of follicles is stimulated by human chorionic gonadotropin. Safety and efficacy of gonadotropin therapy depends on careful monitoring and should only be managed by a specialist.
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Anovulation. Polycystic ovary. Courtesy of Jairo E. Garcia, MD.
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Anovulation. On the left is an unaffected patient aged 12 years. On the right is the same patient aged 13 years after developing Cushing disease.
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Anovulation. Left adrenal mass discovered incidentally.
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Anovulation. MRI showing a nonenhancing area in the pituitary consistent with a microadenoma in a patient with hyperprolactinemia.
