Optimal Treatment for the Surgically Induced Menopausal Patient

1. Optimal Treatment for the Surgically Induced Menopausal Patient By Kerrie Hickman

2. Surgically Induced Menopause=Hysterectomy with Bilateral Oophorectomy • Today approximately 600,000 hysterectomies performed in U.S. Most common age group = 40-44 years old, followed by 35-39. • More than ½ of these women also have both ovaries removed. • Hysterectomies are the second most frequent major surgical procedure among reproductive-aged women (2nd to C-section). • ~1/3 of American women have their uterus removed before the age of 50. (3 most common conditions leading to surgery were fibroid tumors, endometriosis, & uterine prolapse.

4. Mean Steroid Levels in Women(pg/mL)

5. Menopausal Complaints • Hot flashes • Night sweats • Sex organ atrophy (breast and vaginal) • Urogenital changes • Sexual dysfunction & decreased libido

6. Vasomotor Symptoms & Night Sweats -90% of surgically induced menopausal women experience hot flashes compared to the 40% of natural menopause. -Reports also suggest they are more frequent and/or severe. Hot Flashes

7. Postmenopausal Urogenital Changes • Vaginal atrophy of labia minora and majora • Vaginal canal shrinks in length and diameter • pH of vagina increases (allowing more pathogenic bacterial colonization • Decrease in vaginal lubrication • Vaginal mucosa becomes thin and losses elasticity • Distance from urethral opening to vaginal introitus reduces due to tissue atrophy = increase in UTI’s, BV, vaginal dryness, dyspareunia

8. Increase in Disease Associated with Surgical Menopause • Cardiovascular disease/MI • Stroke • Osteoporosis • Clinical Depression *Sarrel PM and Nachtigall LF. Individualizing Hormone Therapy for the Surgically Menopausal Women, Oct 20 2004.

9. The Younger the Woman, the Greater the Concern: Cardiovascular Implications for Younger, Surgically Menopausal Women Relative Risk of Nonfatal MI Findings reported in the American Journal of Obstetrics and Gynecology

10. Management • Hormonal, non-hormonal, or combination therapy • Estrogen only • Lowest dose possible to minimize risks (may need to start at a moderate dose following surgery) • Recent studies suggest low dose systemic estrogens combined with vaginal estrogens are demonstrating desired results with less potential risks. • Do not assume that women on conventional ERT will not have urogenital atrophy. (Rane, 2000) • Patients specific needs plus anticipation of future problems

11. Routes of Administration • Oral- most common, extensive 1st pass metabolism, the liver inactivates 30-90% before it reaches the circulation. (>2fold increase in CRP and reduction in IGF-1) • Stimulates production of coagulation factors • Non-Oral -bypass first-pass metabolism and have a greater bioavailability in smaller dose (coagulation factor production in the liver is prevented) • Silicone vaginal rings-systemic or local effects • Transdermal patches-systemic effects (no effect on CRP) • Vaginal applications- (creams, tablets/suppositories) local effects The route of administration may be an important consideration in minimizing the adverse effects of ET on cardiovascular outcomes.

12. Transdermal Patches • Generics not as good quality (thicker, stiffer, more skin irritation reported) but cheap. • Weekly application • Some you can cut to get desired amount • Won’t lower testosterone • Won’t increase CRP • By-passes first pass metabolism, so can give less estrogen • Expensive

13. Oral Estrogens versus Transdermal Oral Transdermal

15. Vaginal Estrogens • 10-40% women still encounter UG symptoms while on oral systemic estrogens alone. • Local Vaginal estrogens-has been shown to decrease UTI’s by 90%. • Estring, sustained-release ring of estradiol (only 8% absorbed systemically) last 90 days • Creams-may cause substantial increase in blood estrogen levels • Tablets • Systemic vaginalestrogens-unlike oral, it relieves urogenital atrophy without systemic effects. • Femring (silicone ring), treats moderate to severe vasomotor symptoms as well as vaginal atrophy (3 month supply) *This product may be particularly appealing to women who have undergone a hysterectomy because it would be the only product they would need.

16. Nonhormonal Alternatives for Relieving Symptoms of Vaginal Discomfort • Women who are unable or choose to not use estrogen therapy, may find commercially available vaginal lubricants or moisturizers helpful. • Useful in conjunction with HRT. • There is a difference between vaginal lubricant and moisturizer. • Lubricant=temporary relief “Astroglide, Ky, Gyne-Moistrin” • Moisturizer=can restore vaginal moisture and repair dry or damaged vaginal tissue. It also is formulated to lower vaginal pH to normal acidic level. “Replens”

17. The Use of Androgens • Ovaries primarily produce testosterone • Alterations in circulating androgens play a vital role in sexual changes that take place after menopause. • Surgically induced menopausal women develop testosterone deficiency

18. Estrogen + Testosterone • Some hormone therapy includes testosterone but they are too strong! Use care if prescribing. • Estratest – has 4 to 8 times more testosterone than a women should have • Estratest HS – still too much • Research has shown that the testosterone patch can help with sexual function, but much more research is needed. (Proctor & Gamble’s Intrinsa is in Phase III of testing)

19. World Health Initiative (WIH) • In spite of findings, WHI had many shortcomings: • Average age of the women in the WHI was 63 years* • 50% of the study patients were smokers * • WHI evaluated only one dosage • WHI evaluated only one route of administration: oral • Selection criteria focused on chronic diseases and did not include relief of menopausal symptoms • Questions: • Do other routes of administration such as patches and rings have less risks? • Would the results have been different with a more age-appropriate study? • Will lower doses of estrogen and progestin have lower risk?

20. Risks Reported from WHI Study Estrogen/progestin Estrogen alone Breast ca CVD Strokes DVT

21. Summary • Menopausal symptoms more severe for surgically induced menopausal patient • Estrogen only if no uterus • Oral route is not best route • Combination low dose therapy for relief of vaginal symptoms • Not a “one-size fits all” approach to treatment, it should be based on individual symptoms and clinical findings. • Educate patienton risks, benefits, and adverse effects

22. Bibliography Ballagh SA. Vaginal hormone therapy for urogenital and menopausal symptoms. Semin Reprod Med. 2005; 23(2): 126-140.  Ballagh SA. Vaginal ring hormone delivery systems in contraception and menopause. Clin Obstetri and Gyn. 2001, 44:1 pp 106-113.  Doyle, Heidi. Effective topical treatment for atrophic vaginitis. JAPPA Vol 19 No 10: 33-38.  Dull P. Hormone replacement therapy. Primary Care: Clinics in Office Practice Vol 33, No 4; Dec 2006.  Farquhar CM, Steiner CA. Hysterectomy rates in the United States 1990-1997. Obstet Gynecol. Feb 2002; 99(2): 229-34.  Finkel ML. Treatment options for the menopausal woman. The Nurse Practitioner, 2001.  Freeman R, Lewis RM. The therapeutic role of estrogens in postmenopausal women. Endocrinology and Metabolism Clinics Vol 33 No 4; Dec 2004.  Hall G, Phillips TJ. Estrogen and skin: The effects of estrogen, menopause, and hormone replacement therapy on the skin. Journal of the American Academy of Dermatology. Vol 53 No 4;October 2005.  Hillard TC, Whitcroft SJ, Marsh MS, et al. Long-term effects of transdermal and oral hormone replacement therapy on postmenopausal bone loss. Osteoporos Int 1994; 4: 341-8.  Keil K. Urogenital atrophy: Diagnosis, Sequelae, and Management. Current Women's Health Reports 2002, 2:305-311.Am J Obstet Gynecol 1999; 181 (6): 1400-6. Papadopoulos AJ, Shapiro I. Topical Estrogens: An update. Arch Dermatol 2000, Vol 9, No 2.Pinkerton Jv and Santen R. Alternatives to the use of estrogen in postmenopausal women. Endocrine Reviews 2004 (3) 308-320. Rako S. The hormone of desire. New York, 1996.  Shrader SP, Ragucci KR. Life after the Women's Health Initiative: Evaluation of Postmenopausal Symptoms and use of AlteSimon J, Braunstein G, Nachtigall L. Testosterone patch increases sexual activity and desire in surgically menopausal women with hypoactive sexual desire disorder. Journal of Clinical Endocrinology and Metabolism Vol 90 No 9; Sept 2005. rnative Therapies after discontinuation of hormone therapy. Pharmacotherapy 2006; 26(10):1403-1409.  Simon JA. Safety of estrogen/androgen regimens. J Reprod Med. 2001 Mar; 46 (3 Suppl):281-90. Thomas S. Early Menopause. Community Pract. 2006 Aug; 79 (8):236.

23. Kotz K, Alexander JL, and Dennerstein L. Estrogen and androgen hormone therapy and well-being in surgically postmenopausal women. Journal of Women's Health Volume 15, No. 8, 2006. LoBuono C. Vaginal ring treats vasomotor and local symptoms. Drug Topics Apr 21, 2003; 147:24. Nash HA, Alvarez-Sanchez F, Mishell DR, Fraser IS. Estradiol-delivering vaginal rings for hormone replacement therapy. Van der Laak JA, de Bie LM, de Leeuw H, de Wilde PC, and Hanselaar AG. The effects of Replens on vaginal cytology in the treatment of postmenopausal atrophy. Journal of Clinical Pathology. 2002; 55: 446-451. Vongpatanasin W, Tuncel M, Wang Z. Differential effects of oral versus transdermal estrogen replacement therapy on c-reactive protein in postmenopausal women. Journal of the American College of Cardiology Vol 41, No 8 2003. Yuksel N. The Management of vaginal atrophy.