Download Optimal Treatment for the Surgically Induced Menopausal Patient

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.
Relative Risk of Nonfatal MI
The Younger the Woman, the Greater the Concern:
Cardiovascular Implications for Younger, Surgically
Menopausal Women
10
9
8
7
6
5
4
3
2
1
0
Bilateral
oophorectomy
Hys terectomy
without bilateral
oophorectomy
<35
3539
4044
Findings reported in the American Journal of Obstetrics and Gynecology
>44
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
CRP
IGF-1
Oral
increases
increases
decreases
Transdermal
increases
No effect
No effect
Free Testosterone
Cost
Liver Effects
decreases
inexpensive
negative
No effect
expensive
No effect
HDL & LDL
Increase HDL,
decrease LDL
No effect
Triglycerides
increases
No effect
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
Estrogen + Testosterone
Some
hormone therapy includes testosterone but they
are too strong! Use care if prescribing.
– has 4 to 8 times more testosterone than a women
should have
–Estratest
–Estratest
–Research
HS – still too much
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)
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
Estrogen/progestin Estrogen alone
Breast ca
CVD
Strokes
DVT
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
Sign increase
2 fold increase
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
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.
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.