ESTROGEN LEVELS AND GENITOURINARY SIGNS AND SYMPTOMS DURING DMPA USE

1. ESTROGEN LEVELS AND GENITOURINARY SIGNS AND SYMPTOMS DURING DMPA USE Haydarpaşa Numune Education and Research Hospital, Family Planning Unit, Istanbul E.Z. Tuzcular Vural, I. Gönenç, G. Köse, N. Aka

2. Depo-provera has been approved as a contraceptive by the FDA since 1992 and is currently being used in 106 countries by over 9 million women Injectable contraceptives are safe, efficacious and easily applied contraceptives

3. OBJECTIVES • Many studies show that DMPA is a safe, effective and convenient choice of contraception for womenof all age groups • We aimed to identify the the effects of estrogen levels on genitourinary signs and symptoms during depomedroxyprogesterone acetate (DMPA) use in Turkish women

4. The study was based at Haydarpaşa Numune Training and Research Hospital Family Planning Unit/Istanbul The study was planned as a prospectiveobservational non-comparative follow-upstudy. DESIGN AND METHODS

5. Women who desired DMPA for contraception were evaluated before and at 6 months after initiation of DMPA injections . All women were counseled about DMPA and expected side-effects.

6. Inclusion criteria for the study were a minimum of two DMPA injections applied in the same unit and willingness to participate Over a period of 6 months, 74 women fulfilled the criteria and were included in the study.

7. At each visit, we assessed genitourinary signs and symptoms and measured estrodiol levels.

8. RESULTS • Of the 74 subjects receiving their first DMPA injection 48 were followed up for 6 months. • The 48 subjects followed up for 6 months had a mean age of 34.3 ± 5.46 years

9. CHARACTERISTICS OF THE SUBJECTS • primary school education (91.7%) • married (95.8%) • multigravid (97.9%), • regular menses (93.6%) • smokers (20.8%) • The average body mass index (BMI) (kg / m2) was 28.5 ± 4.66 (range 22-39.9).

10. After 6 months, there was significant reduction in mean serum estradiol levels (81.5 ± 22.3 pg/mL to 29.6 ± 14.7 pg/mL, p< 0.0001). The percentage of subjects with very low E2 levels (under 20 pg/mL) increased from 0% at baseline to 22.9% at 6 months. About a fourth of subjects were hypoestrogenic after 6 months of DMPA.

11. Coital frequency did not change throughout the study. External genital pruritus, dyspareunia, dysuria, urinary urgency, and external genitalia burning or pain were infrequent and unchanged . The subjective amount of vaginal discharge reported also did not change.

12. The only parameter with significant difference was an increase in vaginal dryness (p< 0.05). A large proportion of the subjects had regular menses at baseline, but 35.4% were amenorrhoeic after 6 months of DMPA. only one woman had problems with hot flushes (2.1%).

13. There was no correlation between serum E2 levels at 6 months and coital frequency , external genital pruritus, dyspareunia, dysuria, urinary urgency, and external genitalia burning or pain However, all women with vaginal dryness were in the very low E2 level group. There was a positive correlation between serum E2 levels and amenorrhea. Smoking and BMI had no effect on the serum E2 levels at 6 months.

14. Glycogen is produced in estrogen-stimulated vaginal epithelial cells and postmenopausal women have virtually no glycogen in the vaginal epithelium. Glycogen is a very hydrophilic molecule and attracts water into the cell. Reduction of glycogen can cause vaginal dryness.

15. Vaginal dryness is important not only because it lowers the quality of sexual performance but because it may be associated with reduction in the integrity of the mechanical barrier of vaginal epithelium.

16. A recent study has shown a systemic hypoestrogenic state associated with decreased H2O2–positive Lactobacillus colonization and slight thinning of the glycogen vaginal epithelial layer in users of DMPA. Such changes may compromise the vaginal barrier to infection. Miller L, Patton DL, Meier A, Thwin SS, Hooton TM, Eschenbach DA. Depomedroxyprogesterone-induced Hypoestrogenism and Changes in Vaginal Flora and Epithelium . Obstetrics & Gynecology 2000;96:431-9

17. The vagina is considered a critical portal of entry for most sexually transmitted diseases (STDs) in women. Studies in rhesus macaques have shown that subcutaneous progesterone administration by implants resulted in vaginal epithelial thinning and increased simian immunodeficiency virus vaginal transmission Marx PA, Spira AI, Gettie A et al. Progesterone implants enhance SIV vaginal transmission and early virus load. Nat Med 1996; 2:1084–9.

18. Another study showed an increased thickness of the epithelium due to a distended hyperplastic layer in hormonal contraceptive users with increased number of intraepithelial immune cells in DMPA and LNg implant users. Ildgruben AK, Sjöberg IM, Hammarström M-L KC. Influence of Hormonal Contraceptives on the Immune Cells and Thickness of Human Vaginal Epithelium Obstetrics & Gynecology 2003;102:571-582

19. In a study conducted in Thailand ,the authors found that after DMPA use of 59.1 +/- 30.7 months, the mean serum estradiol level was 52.7 +/- 15.1 pg/ml and showed that these women did not have problems of estrogen deficiency Taneepanichskul S,Patrachai S.Effects of long-term treatment with depot medroxy progesterone acetate for contraception on estrogenic activity.J Med Assoc Thai. 1998 ;81(12):944-6.

20. Use of DMPA over 6 months caused a marked reduction in serum E2 levels in our subjects . However, users of DMPA did not have genitourinary tract problems because of estrogen deficiency except vaginal dryness. CONCLUSION

21. Users should be asked about genitourinary signs and symptoms and simple solutions like lubricants or topical estrogen therapy should be offered to prevent dyspareunia and improve sexual performance.

22. THANK YOU..