ESTROGEN LEVELS AND GENITOURINARY ESTROGEN LEVELS AND GENITOURINARY SIGNS AND SYMPTOMS DURING DMPA USESIGNS AND SYMPTOMS DURING DMPA USE

Haydarpaşa Numune Education and Research Haydarpaşa Numune Education and Research Hospital, Family Planning Unit, IstanbulHospital, Family Planning Unit, Istanbul

E.Z. Tuzcular Vural, I. Gönenç, G. Köse, N. AkaE.Z. Tuzcular Vural, I. Gönenç, G. Köse, N. Aka

Injectable contraceptives are safe, efficacious Injectable contraceptives are safe, efficacious and easily applied contraceptivesand easily applied contraceptives

DDepo-provera has epo-provera has been approved as a been approved as a contraceptive by the contraceptive by the FDA since 1992 and FDA since 1992 and is currently being is currently being used in 106 countries used in 106 countries by over 9 million by over 9 million womenwomen

OBJECTIVESOBJECTIVES

Many studies show that DMPA is a safe, Many studies show that DMPA is a safe, effective and convenient choieffective and convenient choicce of e of contraception contraception for for womenwomen of all age groups of all age groups

We aimed to identify the the effects of We aimed to identify the the effects of estrogen levels on genitourinary signs and estrogen levels on genitourinary signs and symptoms during depomedroxyprogesterone symptoms during depomedroxyprogesterone acetate (DMPA) use in Turkish womenacetate (DMPA) use in Turkish women

DESDESIIGN AND METHODSGN AND METHODS

The study was based at The study was based at Haydarpaşa Numune Training Haydarpaşa Numune Training and Research Hospital Family and Research Hospital Family Planning UniPlanning Unit/t/IstanbulIstanbul

The study was planned as aThe study was planned as a pprospectiverospective observational non-observational non-comparative follow-upcomparative follow-up study.study.

Women who desired DMPA for Women who desired DMPA for contraception were evaluated contraception were evaluated before and at 6 months after before and at 6 months after initiation of DMPA injections . initiation of DMPA injections .

All women were counseled about All women were counseled about DMPA and DMPA and expected side-expected side-effects.effects.

Inclusion criteria for the Inclusion criteria for the study were a minimum of study were a minimum of two DMPA injections two DMPA injections applied in the same unitapplied in the same unit and and willingness to participatewillingness to participate

Over a period of 6 months, Over a period of 6 months, 74 women fulfilled the 74 women fulfilled the criteria and were includedcriteria and were included

in the study.in the study.

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

RESULTSRESULTS

Of the 74 subjects receiving their Of the 74 subjects receiving their first DMPA injection 48 were first DMPA injection 48 were followed up for 6 months. followed up for 6 months.

The 48 subjects followed up for 6 The 48 subjects followed up for 6 months had a mean age of 34.3 ± months had a mean age of 34.3 ± 5.46 years 5.46 years

CHARACTERISTICS OF THE CHARACTERISTICS OF THE SUBJECTSSUBJECTS

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

39.9). 39.9).

After 6 months, there was After 6 months, there was significant reduction in mean significant reduction in mean serum estradiol levels (81.5 ± serum estradiol levels (81.5 ± 22.3 pg/mL to 29.6 ± 14.7 22.3 pg/mL to 29.6 ± 14.7 pg/mL, p< 0.0001).pg/mL, p< 0.0001).

The percentage of subjects with The percentage of subjects with very low E2 levels (under 20 very low E2 levels (under 20 pg/mL) increased from 0% at pg/mL) increased from 0% at baseline to 22.9% at 6 months. baseline to 22.9% at 6 months. About a fourth of subjects were About a fourth of subjects were hypoestrogenic after 6 months of hypoestrogenic after 6 months of DMPA. DMPA.

Coital frequency did not change throughout Coital frequency did not change throughout the study. the study.

External genital pruritus, dyspareunia, External genital pruritus, dyspareunia, dysuria, urinary urgency, and external dysuria, urinary urgency, and external genitalia burning or pain were infrequent and genitalia burning or pain were infrequent and unchanged .unchanged .

The subjective amount of vaginal discharge The subjective amount of vaginal discharge reported also did not change.reported also did not change.

The only parameter with The only parameter with significant difference was an significant difference was an increase in vaginal drynessincrease in vaginal dryness

(p< 0.05).(p< 0.05). A large proportion of the subjects A large proportion of the subjects

had regular menses at baseline, had regular menses at baseline, but 35.4% were but 35.4% were amenorrhoeic amenorrhoeic after 6 months of DMPA. after 6 months of DMPA.

only one woman had problems only one woman had problems with hot flushes (2.1%).with hot flushes (2.1%).

There was no correlation between serum E2 There was no correlation between serum E2 levels at 6 months and coital frequency , levels at 6 months and coital frequency , external genital pruritus, dyspareunia, external genital pruritus, dyspareunia, dysuria, urinary urgency, and external dysuria, urinary urgency, and external genitalia burning or pain genitalia burning or pain

However, all women with vaginal dryness However, all women with vaginal dryness were in the very low E2 level group.were in the very low E2 level group.

There was a positive correlation between There was a positive correlation between serum E2 levels and serum E2 levels and amenorrhamenorrhea.ea.

Smoking and BMI had no effect on the Smoking and BMI had no effect on the serum E2 levels at 6 months. serum E2 levels at 6 months.

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. vaginal dryness.

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

A recent study has shown a systemic A recent study has shown a systemic hypoestrogenic state associated with decreased hypoestrogenic state associated with decreased H2O2–positive Lactobacillus colonization and H2O2–positive Lactobacillus colonization and slight thinning of the glycogen vaginal slight thinning of the glycogen vaginal epithelial layer in users of DMPA. Such epithelial layer in users of DMPA. Such changes may compromise the vaginal barrier changes may compromise the vaginal barrier to infection. to infection.

Miller L, Patton DL, Meier A, Thwin SS, Hooton TM, Eschenbach DA. Miller L, Patton DL, Meier A, Thwin SS, Hooton TM, Eschenbach DA.

Depomedroxyprogesterone-induced Hypoestrogenism and Changes in Vaginal Depomedroxyprogesterone-induced Hypoestrogenism and Changes in Vaginal Flora and Epithelium . Obstetrics & Gynecology 2000;96:431-9 Flora and Epithelium . Obstetrics & Gynecology 2000;96:431-9

The vagina is considered a critical portal of The vagina is considered a critical portal of entry for most sexually transmitted diseases entry for most sexually transmitted diseases (STDs) in women. Studies in rhesus macaques (STDs) in women. Studies in rhesus macaques have shown that subcutaneous progesterone have shown that subcutaneous progesterone administration by implants resulted in vaginal administration by implants resulted in vaginal epithelial thinning and increased simian epithelial thinning and increased simian immunodeficiency virus vaginal transmission immunodeficiency virus vaginal transmission

Marx PA, Spira AI, Gettie A et al. Progesterone implants enhance SIV vaginal Marx PA, Spira AI, Gettie A et al. Progesterone implants enhance SIV vaginal transmission and early virus load. Nat Med 1996; 2:1084–9. transmission and early virus load. Nat Med 1996; 2:1084–9.

Another study showed an increased thickness Another study showed an increased thickness of the epithelium due to a distended of the epithelium due to a distended hyperplastic layer in hormonal contraceptive hyperplastic layer in hormonal contraceptive users with increased number of intraepithelial users with increased number of intraepithelial immune cells in DMPA and LNg implant immune cells in DMPA and LNg implant users.users.

Ildgruben AK, Sjöberg IM, Hammarström M-L KC. Influence of Ildgruben AK, Sjöberg IM, Hammarström M-L KC. Influence of Hormonal Contraceptives on the Immune Cells and Thickness of Hormonal Contraceptives on the Immune Cells and Thickness of Human Vaginal Epithelium Obstetrics & Gynecology Human Vaginal Epithelium Obstetrics & Gynecology 2003;102:571-582 2003;102:571-582

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.

CONCLUSCONCLUSIIONON

Use of DMPA over 6 months Use of DMPA over 6 months caused a marked reduction caused a marked reduction in serum E2 levels in our in serum E2 levels in our subjects . subjects .

However, users of DMPA However, users of DMPA did not have genitourinary did not have genitourinary tract problems because of tract problems because of estrogen deficiency except estrogen deficiency except vaginal dryness. vaginal dryness.

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

THANK YOU..THANK YOU..