Optimal Treatment for the Surgically Induced Menopausal Patient

By

Kerrie Hickman

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.

Mean Steroid Levels in Women(pg/mL)

Reproductive Age

Natural Menopause

Surgical Menopause

E2 150 10-15 10

Testosterone 400 290 110

Progesterone 12,000-20,000 <100 <100

Menopausal Complaints

Hot flashes Night sweats Sex organ atrophy (breast and vaginal) Urogenital changes Sexual dysfunction & decreased libido

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.

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

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.

The Younger the Woman, the Greater the Concern: Cardiovascular Implications for Younger, Surgically

Menopausal WomenR

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<35 35-39

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Bilateraloophorectomy

Hysterectomywithout bilateraloophorectomy

Findings reported in the American Journal of Obstetrics and Gynecology

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

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.

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

Oral Estrogens versus Transdermal

Bone Density increases increases

CRP increases No effect

IGF-1 decreases No effect

Free Testosterone decreases No effect

Cost inexpensive expensive

Liver Effects negative No effect

HDL & LDL Increase HDL, decrease LDL

No effect

Triglycerides increases No effect

Oral Transdermal

                                                                                                                           

                                                         

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 vaginal estrogens-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.

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”

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

                                                                      

                

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)

Estrogen + Testosterone

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?

Risks Reported from WHI Study

245 cases vs 185 placebo

94 cases vs 124 placebo

Increased risk No sign. change

Sign. increase in risk

Increased risk 158 vs 118 placebo

2 fold increase Sign increase

Estrogen/progestin Estrogen alone

Breast ca

CVD

Strokes

DVT

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 patient on risks, benefits, and adverse effects

Bibliography 

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