Depomedroxyprogesterone-induced hypoestrogenism and changes in vaginal flora and epithelium

doi:10.1016/S0029-7844(00)00906-6

Obstetrics & Gynecology

Volume 96, Issue 3, 23 August 2000, Pages 431-439

https://doi.org/10.1016/S0029-7844(00)00906-6 Get rights and content

Abstract

Objective: To identify the effects of depomedroxyprogesterone acetate (DMPA) on vaginal microbial flora and epithelium.

Methods: Women who desired DMPA for contraception were evaluated before and at 3 and 6 months after initiation of 150-mg DMPA injections every 3 months. At each visit, we assessed genital symptoms, vaginal signs, vaginal microflora, and histopathology by vaginal biopsies.

Results: Among 38 women observed for 6 months, there was significant reduction in mean serum estradiol level (99.9 ± 9.3 pg/mL to 26.6 ± 1.6 pg/mL, P < .001). The number of subjects with any Lactobacillus did not change, but the number with hydrogen peroxide (H₂O₂)–positive Lactobacillus decreased from 20% before to 12% after 6 months of DMPA (P = .005). The log concentration in colony-forming units per milliliter of vaginal fluid of H₂O₂–positive Lactobacillus decreased in a linear manner from 4.0 ± 0.6 at baseline to 2.5 ± 0.6 after 6 months of DMPA use (P = .006). The mean number of cell layers in the epithelium was reduced slightly from 28.1 ± 0.7 to 25.9 ± 0.9 (P = .05), epithelial thickness decreased from 1.02 ± 0.04 mm to 0.89 ± 0.05 mm (P = .005), and the glycogen-positive thickness decreased from 0.81 ± 0.04 mm at baseline to 0.66 ± 0.05 after 6 months of DMPA use (P = .005).

Conclusion: Depomedroxyprogesterone acetate produced a systemic hypoestrogenic state associated with decreased H₂O₂–positive Lactobacillus colonization and slight thinning of the glycogen vaginal epithelial layer. Such changes possibly compromise the vaginal barrier to infection.

Section snippets

Materials and methods

From October 1996 to February 1999, subjects were enrolled from the University of Washington student and staff population. Recruitment was through newspaper ads, flyers, and word-of-mouth referrals. Women were eligible for the study if they planned to use DMPA for contraception, were 18–40 years old, had regular menses, had a single or no male sexual partner, and agreed to refrain from vaginal medications. Exclusion criteria were abnormal vaginal discharge, complaints of vaginitis, chronic

Results

Among 60 women screened, 58 received the first DMPA injection and 38 were followed up for 6 months. We focused on those 38 subjects. Among the 20 subjects who were observed less than 6 months, nine did not return or moved, six changed contraception (one for pregnancy and five for nonadverse effect reasons), three others had adverse effects, and two were still observed but missed 6-month visit. The 38 subjects followed up for 6 months had a mean (± standard error of the mean) age of 22.1 ± 0.8

Discussion

Depomedroxyprogesterone acetate over 6 months caused a marked reduction in serum E2 levels in our subjects (Table 3), findings that were documented previously.2, 3, 5 The percentage of subjects with very low E2 levels (under 20 pg/mL)21 increased from 3% at baseline to 34% at 6 months. Over one third of subjects were hypoestrogenic after 6 months of DMPA. A single E2 measurement was shown to be a valid measure of the estrogen milieu of DMPA users because the measurement of daily E2 levels

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^☆: Supported by National Institutes of Health grant 1 R01 HD33203.

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Original articleDepomedroxyprogesterone-induced hypoestrogenism and changes in vaginal flora and epithelium☆

Abstract

Section snippets

Materials and methods

Results

Discussion

Obstet Gynecol

Am J Obstet Gynecol

Lancet

Am J Obstet Gynecol

Contraception

Am J Obstet Gynecol

Contraception

Contraceptive technology

Pharmacokinetics of depot medroxyprogesterone acetate contraception

J Reprod Med

Endometrial histology and circulating levels of medroxyprogesterone acetate, estradiol, FSH and LH in women with MPA induced amenorrhea compared with women with secondary amenorrhea

Acta Obstet Gynecol Scand

Progesterone implants enhance simian immunodeficiency virus vaginal transmission and early viral load

Nature Med

Effects of two progestin only contraceptives, Depo-Provera, and Norplant II, on the vaginal epithelium of rhesus monkeys

AIDS Res Hum Retroviruses

Determinants of HIV infection among female commercial sex workers in northeastern ThailandResults from a longitudinal study

J Acquir Immune Defic Syndr Hum Retrovirol

Hormonal contraception, sexually transmitted diseases, and risk of heterosexual transmission of human immunodeficiency virus type 1

J Infect Dis

Contraceptive use and the risk of HIV infection in Nairobi, Kenya

Int J Gynaecol Obstet

The incidence of HIV infection among women using family planning methods in Dar es Sallam, Tanzania

AIDS

Viricidal effect of Lactobacillus acidophilus on human immunodeficiency virus type 1Possible role in heterosexual transmission

J Exp Med

Vaginal lactobacilli, microbial flora, and risk of human immunodeficiency virus type 1 and sexually transmitted disease acquisition

J Infect Dis

Original article
Depomedroxyprogesterone-induced hypoestrogenism and changes in vaginal flora and epithelium☆