1. Postmenopausal vaginal atrophy
Presentation by the International Menopause Society for World Menopause Day October 18th, 2010

2. Urogenital atrophy Estrogen receptors present in: Vagina Urethra
Bladder trigone
Pelvic floor

3. Döderlein's lactobacilli convert glycogen from sloughed vaginal cells
Glycogen formation
Mucus layer
Vaginal pH ( )
Lactic acid
Protects from: Streptococcus Staphylococcus Coliform Diphtheroid infections
Estrogen
Maintains thickness of squamous vaginal epithelium, rugae, pink color, and moisture
Proliferation of connective tissue Fragmentation of elastin Hyalanization of collagen

4. Postmenopausal changes in the vaginal epithelium4
Postmenopausal changes in the vaginal epithelium
PREMENOPAUSAL
POSTMENOPAUSAL
Erectile tissue
Folds or rugae
Loss of folds
Muscular coat
Loss of inner lining and glandular function
Inner lining contains large amount glycogen
Samsioe G. A profile of the Menopause, 1995:49 (Figure 6.4) 4

5. Vaginal histology H & E, magnification  10 Premenopause5
Vaginal histology
H & E, magnification  10
Premenopause
Well-estrogenized epithelium, multi-layered with good blood supply; superficial cells rich in glycogen
Postmenopause
Estrogen-deficiency atrophy with marked thinning of the epithelium, reduced blood supply and loss of glycogen 5

6. Vaginal wall smear under the microscope6
Vaginal wall smear under the microscope
Normal:
Superficial cells predominate
Low nuclear/cytoplasmic ratio
Pyknotic nuclei
Atrophic:
More parabasal cells
High nuclear/cytoplasmic ratio
Inflammatory exudate 6

7. Symptoms of urogenital atrophy
Vaginal
Dryness
Burning
Pruritus
Dyspareunia
Prolapse
Urinary
Urgency
Frequency
Dysuria
Urinary tract infection
Incontinence
Voiding difficulties

8. Prevalence of symptoms in women treated for breast cancer
Menopause Rating Scale; n = 200
Symptom
Symptoms (%)
Moderate – severe (%)
Hot flushes/sweats 85 63
Sexual problems 60 45
Urinary problems 55 39
Vaginal dryness 34
Gupta P, et al. Climacteric 2006;9:49–58

9. Increase in vaginal dryness with menopause
47%
32%
25%
21% 3% 4%
Pre- menopause
(n = 172)
Early perimenopause
(n = 148)
Late perimenopause
(n = 106)
Post- menopause 1 year
(n = 72)
Post- menopause 2 years
(n = 54)
Post- menopause 3 years
(n = 31)
Dryness increased significantly in late perimenopause and postmenopause (p <0 .001)
Dennerstein L, et al. Obstet Gynecol 2000;96:351–8
1Dennerstein L, Dudley EC, Hopper JL, Guthrie JR, Burger HG. A prospective population-based study of menopausal symptoms. Obstet Gynecol. 2000;96: 9

10. Prevalence of superficial dyspareunia and vulvovaginal atrophy by menopausal age
Perimenopause
(n = 133)
0–1 year
(n = 52)
2–3 years
(n = 39)
4 years
(n = 67)
Atrophy increased significantly with increase in menopausal age (p <0 .001)
Adapted from Versi E, et al. Int Urogynecol J 2001;12:107–10
1Sadovsky R. Management of Dyspareunia and Vaginismus. Am Fam Physician Available at: tips/21.html. Accessed January 6, 2003.
2Versi E, Harvey M-A, Cardozo L, Brincat M, Studd JWW. Urogenital prolapse and atrophy at menopause: a prevalence study. Int Urogynecol J. 2001;12: 10

11. Dyspareunia (intensity)
Lower estrogen levels are associated with increased prevalence of sexual problems 60
<184 pmol/l (50pg/ml) estradiol
>184 pmol/l (50pg/ml) estradiol 50 40 30
% Reporting problems 20 10
Vaginal dryness
Bothered by problem
Dyspareunia (intensity)
Pain with penetration
Burning
n = 93; significance not reported
Sarrel PM. J Womens Health Gend Based Med 2000;9:S25–32
Adapted from Sarrel PM. Obstet Gynecol 1990;75(4 Suppl):26–30S
1Sarrel PM. Effects of hormone replacement therapy on sexual psychophysiology and behavior in postmenopause. J Womens Health Gend Based Med. 2000;9:S25-S32.
2Sarrel PM. Sexuality and menopause. Obstet Gynecol. 1990;75:26S-30S. 11

12. Prevalence of vaginal atrophy
Up to 40% of postmenopausal women experience vaginal atrophy
Only 25% of them seek medical assistance
Bachman GA, et al. Am Fam Physician 2000;61:3090–6
Cardozo L, et al. Obstet Gynecol 1998;92:722–7

13. How to discuss vaginal atrophy with postmenopausal women (1)
Health-care professionals are not asking postmenopausal women about problems such as vaginal dryness
Initiate the discussion about vaginal dryness; your patient may be reluctant
Consider that relationship/sexual issues may present as vaginal discomfort

14. How to discuss vaginal atrophy with postmenopausal women (2)
Remember that women using systemic estrogen therapy can still develop vaginal symptoms
Be mindful that some urinary symptoms occur concurrently with vaginal atrophy and also respond positively to vaginal estrogen therapy
Encourage women to select a vaginal therapy most comfortable for them

15. Principles of treatment
Restoration of urogenital physiology
Alleviation of symptoms

16. Treatment of vaginal atrophy (1)
Vaginal moisturizers:
Primarily used to relieve vaginal dryness during intercourse
Do not provide a long-term solution

17. Treatment of vaginal atrophy (2)
Local/topical estrogen:
Logical treatment
Pessaries/vagitories, creams, tablets, or ring
Systemic estrogen

18. Menopausal women suffering from atrophic vaginitis18
Menopausal women suffering from atrophic vaginitis
Physician‘s perspective:
Women without systemic HRT
Women with systemic HRT
Patients suffering from atrophic vaginitis
Patients not suffering from atrophic vaginitis
39%
27%
61%
73%
Over half of postmenopausal women will have urogenital discomfort associated with estrogen deficiency
Although many women use oral hormone replacement therapy, urogenital symptoms persist
Notelovitz M, et al. Obstet Gynecol 2002;99:556–62 18

19. Systemic HRT concerns Breast cancer Endometrial cancer
Venous thromboembolism
Stroke

20. How much local estrogen is absorbed into the circulation?
Effects on other tissues
Safety implications
Duration of treatment
Difficulty in measuring estrogens other than 17β-estradiol

21. Endometrial and vaginal effects of low-dose estradiol delivered by vaginal ring or vaginal tablet
Estring (Pharmacia Upjohn), silastic vaginal ring containing 2 mg 17β-estradiol, releasing 8 µg per 24 h over 90 days (n = 126)
Vagifem (Novo Nordisk), mucoadhesive tablet containing 25 µg 17β-estradiol (n = 59)
Mean age = 58 (46–81) years
Weisberg E, et al. Climacteric 2005;8:83–92

22. Estrogen levels during vaginal therapy
Weeks 24 48
Estring
Estradiol (pmol/l)
16 ± 22
49 ± 64
20 ± 19
Estrone (nmol/l)
1.0 ± 0.67
1.4 ± 0.86
1.57 ± 0.89
Vagifem
15 ± 33
36 ± 51
36 ± 50
Estrone (nmol/l)
1.14 ± 1.76
1.39 ± 0.82
1.69 ± 1.48
Weisberg E, et al. Climacteric 2005;8:83–92

23. Endometrial thickness during vaginal estrogen therapy
Weeks 48
Estring (mm)
[range]
2.5
[ ]
2.6
[ ]
Vagifem (mm)
[ ]
2.7
[ ]
Weisberg E, et al. Climacteric 2005;8:83–92

24. Endometrial and vaginal effects of low-dose estradiol delivered by vaginal ring or vaginal tablet
Conclusion
Equivalent endometrial safety and efficacy in the relief of the symptoms and signs of urogenital estrogen deficiency were demonstrated for the 12 months’ use of both preparations
Weisberg E, et al. Climacteric 2005;8:83–92

25. Endometrial histology: Vagifem vs. CEE cream
(n = 159 treated for 24 weeks)
Rioux JE, et al. Menopause 2000;7:156–61

26. Conclusions and recommendations (1)
Treatment should be started early and before irrevocable atrophic changes have occurred
Treatment needs to be continued to maintain the benefits
All local estrogen preparations are effective and patient preference will usually determine the treatment used

27. Conclusions and recommendations (2)
Delay in starting local treatment will reduce degree of response
Initial loading dose to stimulate receptors followed by low maintenance dose once or twice per week

28. Conclusions and recommendations (3)
Additional progestogen is not indicated when appropriate low-dose, local estrogen is used, although long-term data (more than 1 year) are lacking

29. Conclusions and recommendations (4)
Following gynecological cancer, the use of local estrogen may not be contraindicated; these women should receive appropriate counselling regarding the risks and benefits, taking into account their individual risk factors
Use of local estrogen therapy in women on tamoxifen or aromatase inhibitors needs careful counselling and discussion with the oncology team

30. Further reading www.imsociety.org
IMS Writing Group. Recommendations for the management of postmenopausal vaginal atrophy. Climacteric 2010;13:509–22