New Options for Moderate-to-Severe Menopausal Symptoms

Dr. Pino is an assistant professor of pharmacy practice at Lloyd L. Gregory School of Pharmacy, Palm Beach Atlantic University, West Palm Beach, Fla.

The North American MenopauseSociety (NAMS) statesthat menopause should beregarded as a natural biologicalprocess and not a specific diseaseentity.1 The menopausal transition is aprocess that can last severalyears and is often associatedwith numerous undesirablemanifestations.The MenopauseTime FrameThe median age of onsetof menopause in theUnited States is 51 years.Prior to menopause is thetransition period known asperimenopause.2 Perimenopauseis characterized byirregular uterine bleedingdue to oligo/anovulationand is often marked by theonset of menopausal symptoms.Menopause is definedas the permanent cessation ofmenses secondary to the loss of ovarianfollicular activity. It is characterizedby a change in circulating hormoneconcentrations, such as a morethan 10-fold increase in follicle-stimulatinghormone (FSH) and a more than4-fold increase in luteinizing hormonelevels. Menopause is often diagnosedretrospectively after 12 months withoutmenstrual periods in the absenceof any other cause for amenorrheaand by the presence of vasomotorsymptoms such as hot flashes. A thoroughmedical history, physical examination,and FSH serum level shouldconfirm the diagnosis.3 The clinicalpresentation of menopause mayinclude vasomotor symptoms, genitourinaryatrophy, nausea, headache,dizziness, sleep disturbances, moodchanges, and/or sexual dysfunction.4Managing Symptoms ofMenopause

Hormone therapy (HT) options formenopausal symptoms include estrogentherapy (ET) and combined estrogenplus progestins. Alternative therapiesfor patients in which HT is contraindicatedare also available.

Although HT is currently the mosteffective treatment for menopausalsymptoms, the Women?s HealthInitiative, a National Institutes ofHealth?sponsored randomized clinicaltrial, found that therewas an increased risk ofcardiovascular disease andbreast cancer in some patientsassociated with combinedconjugated equineestrogen plus medroxyprogesteroneacetate.5,6Since the publication of thisstudy, concerns regardingthe safety and long-termconsequences of HT havemade its use controversial.Despite this, both theAmerican College of Obstetriciansand Gynecologistsand NAMShave issued statementsindicating that the short-termuse of HT may still be appropriatefor the relief of vasomotor symptomsin certain patients.1,7 Health careproviders should keep in mind thatthe decision to start or continue HTmust be individualized, based on acomplete clinical assessment, andconsider the benefits, risks, and alternativesavailable to each woman.Absolute contraindications to HT includeundiagnosed vaginal bleeding,pregnancy, estrogen-dependent malignancies,known or suspectedbreast cancer, and active thromboembolicdisorders. Common adverseeffects include nausea, hypertriglyceridemia,edema, breast tenderness,mood swings, and acne.3

HT is indicated for thetreatment of moderate-to-severevasomotor symptomsassociated with menopauseand moderate-to-severevulvovaginal atrophyassociated with themenopause. These symptomsare described as"intolerable" by 10% to20% of the women whoexperience them and canseverely impact a woman?squality of life. Hot flashesare often described as asensation of warmth, frequentlyaccompanied byskin flushing and perspiration,and may be followedby a chill. These may occurin women of any age whoexperience acute estrogenwithdrawal and can last more than 5years in up to 75% of affected women.Urogenital symptoms, such asvaginal dryness, also detract from awoman?s quality of life and causemany to seek treatment.8

Studies have shown ET to be effectivein the treatment of moderate-to-severevasomotor menopausal symptoms.Systemic estrogen therapy isalso associated with several otherbenefits, including the prevention ofpostmenopausal osteoporosis. Estrogenmonotherapy should be restrictedto patients who have undergone ahysterectomy due to the risk ofendometrial hyperplasia. Womenshould be given the lowest estrogendose necessary to help alleviatesymptoms, and the length of therapyshould be limited to the shortest possibleduration. Commonly used systemicestrogen formulations includeconjugated equine estrogens, micronized17?-estradiol, and ethinyl estradiol.9

The primary menopause-relatedindication for progestin use isendometrial protection from unopposedestrogen therapy. Unopposedestrogen therapy in women with anintact uterus significantly increasesthe risk for endometrial cancer.Progestins can be prescribed continuouslyor cyclically. In some cyclic regimens,estrogen is administered dailyand a progestin is added for 14 dayseach month. Some commonly usedprogestins include medroxyprogesteroneacetate (MPA), micronizedprogesterone, norethindrone, andlevonorgestrel.9,10 Side effects tend tovary among these agents but mayinclude mood swings, bloating, fluidretention, and sleep disturbances.3Options for MenopausalSymptoms

A novel progestin, drospirenone, iscurrently being used incombination with estradiolfor the treatment of moderate-to-severe vasomotorsymptoms associated withmenopause. Drospirenoneis a spironolactone analogwith antialdosterone andantimineralocorticoid activity.It has a pharmacologicprofile that is more similarto endogenous progesteronethan that of otheravailable progestins. Drospirenoneis currently usedin oral contraceptives andcan also be found in thecombination HT productAngeliq (drospirenone/estradiol).12

Angeliq contains 1 mg ofestradiol with 0.5 mg ofdrospirenone and is indicated for thetreatment of moderate-to-severevasomotor symptoms as well as thetreatment of moderate-to-severesymptoms of vulvar and vaginal atrophyassociated with menopause. Thiscombination product is effective inreducing these symptoms withoutcausing an increase in the incidenceof endometrial hyperplasia at 1 year.

Angeliq may be a treatment optionfor the effective management ofmenopausal symptoms in appropriatewomen.References

1. Estrogen and progestogen use in peri- and postmenopausal women: March 2007 position statement of the North American Menopause Society. Menopause. 2007;14:168-182.

2. Blake J. Menopause: evidence-based practice. Best Pract Res Clin Obstet Gynaecol. 2006;20(6):799-839.

3. Kalantaridou S, Davis SR, Calis KA. Hormone therapy in women. In: Dipiro JT, Talbert RC, Yee GC, et al. 6th ed. Pharmacotherapy: A Pathophysiologic Approach. New York, NY: McGraw-Hill; 2005.

4. Santoro N. The menopausal transition. Am J Med. 2005;118(suppl 12B):8-13.

5. Manson, JE, Hsia J, Johnson KC, et al: Women?s Health Initiative Investigators. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med. 2003;349: 523-524.

6. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefit of estrogen plus progestin in healthy postmenopausal women; principal results from Women?s Health Initiative randomized control trial. JAMA. 2002;288:321-333.

7. North American Menopause Society. Treatment of menopause-associated vasomotor symptoms: position statement of the North American Menopause Society. Menopause. 2004;11(1):11-33.

8. American College of Obstetricians and Gynecologists. Vasomotor symptoms in hormone therapy. Obstet Gynecol. 2004;104(suppl):106S-117S.

9. AACE Menopause Guidelines Revision Task Force. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of menopause. Endocr Pract. 2006;12(3):315-337.

10. Brigham and Women?s Hospital. Menopause: A guide to management. Boston, Mass. Brigham and Women?s Hospital; 2005.

11. Foidart JM. Added benefits of drospirenone for compliance. Climacteric. 2005 Oct(8 suppl 3):28-34.

12. Archer DF. Drospirenone and estradiol: a new option for menopausal women. Climacteric. 2007 Feb(10 suppl 1):3-10.