Gynaecology 2011

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Should the LNG-IUS be the contraceptive of choice in women with recurrent vaginitis? Gilbert G.G. Donders, Gert Bellen Femicare Foundation, Clinical Research for Women, Tienen, Belgium; Department of Obstetrics and Gynaecology, Heilig Hart Hospital, Tienen, Belgium; Department of Obstetrics and Gynaecology, Gasthuisberg University Hospital, Leuven, Belgium ([email protected])

Introduction

causing frustration and fear of transmitting the infection to others, thus adversely affecting the woman’s sex life.

Vulvovaginitis can be a very disturbing condition. In the overwhelming majority of cases, candidiasis is caused by Candida albicans, although non-albicans species such as C. galbrata, C. parpsilosis and C. krusei may also occur, especially in women receiving prophylactic therapy for chronic recurrent disease. Bacterial vaginosis is another troublesome disease with a tendency to recur often, so that in some women it seems never fully to disappear. It is due to an ecological disturbance of the vaginal flora, wherein the lactic acid bacteria are replaced by large quantities of Gardnerella vaginalis, Atopobium vaginalis, Mobiluncus sp. and other anaerobes. Its most typical symptom is a persistent, fishy smell and a discharge that is often less typical than the ‘profuse homogenous watery grey discharge’ that is so often quoted in textbooks. Trichomonas vaginalis is an obligate sexually transmitted parasite that may cause symptomatic or asymptomatic disease in both men and women. Its prevalence in Europe and North America has dramatically reduced in recent decades and it now affects 0.5–1.0% of the population. Aerobic vaginitis is a condition with diminished lactobacillary morphotypes, increased signs of inflammation and the presence of aerobic, enteric bacteria, such as Escherichia coli, group B streptococci, staphylococci and others. Its symptoms, pathogenesis and diagnostic characteristics differ dramatically from those of bacterial vaginosis, but mixed infections where both bacterial vaginosis and aerobic vaginitis co-occur may exist. For all these types of vulvovaginitis, effective medication is available that usually rapidly alleviates the symptoms and cures the condition. However, some of these conditions have a tendency to recur frequently,

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Could the choice of contraceptive method be a potential risk factor for vaginal infections? It is understandable that women with recurrent vulvovaginal infections due to bacterial vaginosis, recurrent Candida vaginitis and aerobic vaginitis often try all means to diminish the likelihood of recurrence. Many women, and their physicians, suspect that their method of contraception, such as the Pill or the copper-containing intrauterine device (IUD) is a possible risk factor [1], leaving the best choice of contraceptive an open question for many affected women. In a previous study we reported that a majority of women suffering from chronic recurrent vaginal candidiasis found that replacing low-dosage contraceptive pills with another method was beneficial. Replacement of estrogen-containing methods by progestogen-only methods may be beneficial in some women [2]. Furthermore, in those using the copper IUD, bacterial vaginosis may be more frequent, perhaps triggered by the longer, more frequent and abundant menstrual flow [3].

Retrospective study into the effect of the LNG-IUS on vaginal bacterial flora As up to 85% of women using the levonorgestrelreleasing intrauterine device (LNG-IUS; Mirena®) become amenorrhoeic after 4 months, or bleed only sporadically [4–8], we hypothesized that the LNGIUS might have a beneficial effect on the vaginal

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bacterial flora, decreasing the likelihood of developing or supporting bacterial vaginosis and aerobic vaginitis. To study whether use of the LNG-IUS as a contraceptive method would decrease the likelihood of Candida colonization and of bacterial vaginosis in normal unselected women seeking contraceptive advice, we performed a retrospective pilot study to assess vaginal microflora before and after LNG-IUS placement.

layer smears kept in liquid medium than in conventional smears, we performed some analyses with and without monolayer smears. As for bacterial vaginosis, to achieve comparability the diagnosis of aerobic vaginitis was also based purely on microscopy findings [12]. Lactobacillary grades are the basis of a composite score (known as the aerobic vaginitis or AV score), to which an assessment of the four following variables is added, as described elsewhere [12]: presence of leukocytes, presence of toxic leukocytes, presence of parabasal cells, and presence of background flora. Severity was then categorized according to a composite score (AV score): AV score ≤2 = normal; AV score 3–4 = light aerobic vaginitis; AV score 5–6 = moderate aerobic vaginitis; AV score >6 (to a maximum of 10) = severe aerobic vaginitis. An AV score of 8–10 is usually equivalent to so-called ‘desquamative vaginitis’, representing the most extreme form of aerobic vaginitis [13–15]. Bacterial vaginosis was diagnosed as the presence of G. vaginalis or Mobiluncus morphotypes and/or clue cells, in combination with the absence of lactobacilli (LBG III). This diagnosis can be reliably compared with a Nugent score >6 on Gram stains [9, 10]. The presence of Candida was noted as either absent or present. When Candida was present, notes were made of the presence of blastospores, pseudohyphae or a combination of both. Recognition of Candida from the Pap stain was not always easy, which probably led to underreporting. Therefore, a subgroup termed ‘probably Candida’ was made of cases with possible or partial evidence, but no pathognomonic proof that Candida was present.

“As up to 85% of women using the LNG-IUS become amenorrhoeic after 4 months, or bleed only sporadically, we hypothesized that the LNG-IUS might have a beneficial effect on the vaginal bacterial flora, decreasing the likelihood of developing or supporting bacterial vaginosis and aerobic vaginitis.”

Method A Pap smear was taken in 286 patients 1–12 months before insertion of the LNG-IUS at the outpatient gynaecology clinic of Heilig Hart Tienen general hospital in Belgium, between June 1997 and September 2008; a second Pap smear was taken 1–2 years after insertion. Microscopy was performed on all numbered, unnamed Pap smears by an investigator who had no knowledge of either the timing of sampling or the identity of the individual. The microbial flora was classified according to Schröder’s original classification, further refined by Donders [9]. Normal, grade I flora (LBG I) corresponds predominantly to lactobacillary morphotypes, with the presence of very few coccoid bacteria. Intermediate grade II flora (LBG II) corresponds to diminished lactobacillary flora mixed with other bacteria. This group was subdivided into slightly disturbed, fairly normal (LBG IIa) and moderately disturbed, somewhat abnormal (LBG IIb) lactobacillary flora. Finally, abnormal grade III flora (LBG III) consists of numerous other bacteria, with no lactobacilli present. This scoring system was used because of its merits in describing the host response and enabling the study of vaginal pathogens and predicting pregnancy complications [10]. In some patients, due to recent use of vaginal douches, antibacterial medication or the technique of preparing the Pap smear [11], all traces of bacterial flora may be wiped out, making proper diagnosis difficult or impossible. Such smears devoid of microflora are defined as LBG 0. As this flora type can be present more often in mono-


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Results Before insertion of the LNG-IUS, bacterial vaginosis was found in 4.3% of the study population, aerobic vaginitis microflora in 10.5% and Candida colonization in 4.2%. These figures were 8%, 12.6% and 5.9%, respectively, after insertion [16]. Abnormal vaginal flora, an indicator of disturbed lactobacillary resistance, was found in 26% before insertion and in 32% after insertion. There were no major fluctuations in infection rates of patients according to the former contraceptive used in the study group: the prevalence of aerobic vaginitis, bacterial vaginosis and Candida vaginitis was similar in former combined estrogenprogestogen users, former progestogen-only users, former LNG-IUS users, postpartum patients and in women who were not using any contraception (Table I). No single vaginal infection became significantly more frequent 1–2 years after insertion of the LNGIUS. However, in patients using the LNG-IUS for the first time, the prevalence of all infections combined

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Table I: Types of abnormal flora in patients before and 1 year after insertion of the LNG-IUS. In patients using the LNG-IUS for the first time, the prevalence of all infections combined (C. albicans, aerobic vaginitis, bacterial vaginosis) was 38/231 (16.5%) before insertion vs. 59/231 (25.6%) after 1 year (OR 1.7, 1.1–2.8; p = 0.02). Adapted from [16]. Previous method of contraception

LBG IIb–III (abnormal)

n

Before

Bacterial vaginosis

After

Before

After

Aerobic vaginitis (AV score ≥4) Before

After

Candida colonization

Before

After

None

20

3

4

2

1

1

2

0

3

LNG-IUS

55

17

15

3

5

11

8

3

4

Other

211

54

71

8

17

18

26

9

10

Total (%)

286 (100)

74 (25.9)

90 (31.5)

23 (8.0)

30 (10.5)

36 (12.6)

13 (4.5)

(C. albicans, aerobic vaginitis and/or bacterial vaginosis) was 38/231 (16.5%) before insertion vs. 59/231 (25.6%) after 1 year (OR 1.7, 1.1–2.8; p = 0.02). Among new LNG-IUS users with conventional smears, 37/194 (19.1%) had one or more of those infections at insertion compared with 57/194 (29.4%) after 1 year (OR 1.7, 1.2–2.8; p = 0.02). The amount and type of bleeding did not influence the bacterial microflora. In women with abnormal flora, normal flora or absent flora the rate of amenorrhoea was around 60%. On the other hand, abnormal vaginal flora was not more frequent in women with moderate to excessive bleeding (32.4%) than in women with amenorrhoea (33.3%).

17 (5.9)

and intermediate bacterial flora (defined as score 4–6 in the Nugent system) were more frequent in copper IUD users than in either Pill users or those not using contraception [21], suggesting that the copper IUD more readily destabilizes the vaginal microflora. On Candida infection rates, however, conflicting data have been published. In some studies Candida rates increased with the duration of use of the LNG-IUS, while in other studies Candida rates were lower than in oral contraceptive users [21, 22]. On the one hand, the presence of a foreign body may theoretically support the growth of latent Candida infection, and even promote its ascent into the uterine cavity, leading to tubo-ovarian abscesses [17, 23] or mid-trimester abortion due to Candida chorioamnionitis and funisitis occurring during pregnancy [24–30]. On the other hand, the release of progestogens, as with the LNGIUS, may exert a suppressive action on its growth or formation of mycelium structures [2]. Due to the decreasing amount of menstrual flow, one may expect bacterial vaginosis to decrease, while Candida colonization may either increase (foreign body hypothesis) or decrease (changed local estrogen/ progestogen ratio hypothesis). In our retrospective cohort study using Pap smears before and after LNGIUS insertion we detected no specific differences in colonization or infection rates of Candida vaginitis, bacterial vaginosis or aerobic vaginitis. Women using other contraceptives before insertion also had comparable infection rates for these infections to those of women with previous LNG-IUS use. However, taken together and adjusted for previous LNG-IUS use and different Pap smear preparation techniques, we found a significant increase in the colonization/infection rate 1–2 years after LNG-IUS insertion. Of note, the hypothesis that levonorgestrel-containing intrauterine devices causing amenorrhoea would diminish bacterial vaginosis and increase Candida vaginitis could not be proved.

Other investigations into a link between contraceptive method and vaginal infections There is no consensus on which contraceptive method is most suitable for women with recurrent bacterial and fungal infections of the vagina. Due to the omission of exogenous estrogens on the one hand, and the decrease in menstrual blood flow on the other, the LNG-IUS may have an influence on the stability and resistance of the vaginal flora. Pelvic inflammatory infections occur more often during the first month after insertion of an intrauterine contraceptive device, especially the copper IUD [17]. In most studies, after the first month of use, the upper genital tract infection rate is similar to that in women using other or no contraception, with the exception of Actinomyces israelii infection [18], which may occur more often after long-term use of the copper IUD, but not of the LNG-IUS [19]. Bacterial vaginosis is found more often in copper IUD users, especially after 4 years of use [3], but not in LNG-IUS users [3, 20], when compared with Pill users or nonusers of contraception. Vaginal overgrowth of E. coli

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12 (4.2)

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Concluding remarks

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We are currently analysing the data of a prospective study of vaginal infections, colonization and abnormal vaginal flora by wet mount and cultures in 251 women before and after insertion of the LNG-IUS. At inclusion, women who had used the LNG-IUS for 5 years and required a replacement were compared with previous non-users or Pill users. There was no difference in any of the infections discussed above, neither singly nor combined. This led us to the conclusion that the LNG-IUS does not alter the vaginal flora, even after 5 or more years of use. Hence, from both studies we conclude that in LNGIUS users there is no difference in the rates of any specific microscopic bacterial abnormalities and Candida colonization in the vaginal microflora. There may be a general increased risk of vaginal flora abnormalities after 1 year, but analysis of entry data of the prospective trial also confirm there is no global rise in the risk of vaginal infection 5 years after insertion.

“We conclude that in LNG-IUS users there is no difference in the rates of any specific microscopic bacterial abnormalities and Candida colonization in the vaginal microflora.”

Acknowledgment This research is sponsored by the Femicare Foundation, a non-profit-making organization supporting clinical research in women.

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