Giorn. It. Ost. Gin. Giornale Italiano di Ostetricia e Ginecologia CIC Edizioni Internazionali 2013 September-October; 35(5): 679–683. ISSN: 0391-9013
Published online 2013 October 30.

Vaginal cytology: a marker of hormone therapy in transsexuals

A.M. CARINGELLA,1 L. RESTA,2 M. DELLINO,1 F. SCARAMUZZI,1 R. DE NOLA,1 E. SILVESTRIS,1 G. INGRAVALLO,2 and G. LOVERRO1

University of Bari “Aldo Moro”, Bari, Italy

1 II Unit of Obstetrics and Gynecology, DIMO
2 Department of Pathology

Corresponding Author: Prof. Giuseppe Loverro, giuseppe.loverro@uniba.it, tel-fax: +39 080 5592228

Abstract

Introduction.
Transsexualism is a gender identity disorder characterized by constant discomfort for their assigned sex and the desire to live and be accepted as a member of the opposite sex, this persistently for the last two years (definition DMS IV).

The administration of androgens (testosterone) is usually the first step in the sex reassignment somatic Trans FtM, unlike patients MtF make estrogen therapy (oral or topical).

Only a few studies describe the cytology in MtF with different opinions, there are no data available on the cytology in the FtM.

Objectives.
The primary objective was to describe the vaginal/vulvovaginal cytology not only in female transsexuals but also in the FtMs. The secondary objective was to compare the results of cytology in MtF and FtM with the evaluation of estrogen, with the ultimate aim of assessing whether the cytology may be useful for the hormone treatment follow-up.

Materials and methods.
We enrolled 22 transsexuals to investigate the relationship between serum hormone levels, hormone dose administered and the degree of vaginal estrogen assessment. Of the 22 subjects enrolled, 8 were part of MtF and 14 FtM group.

Results.
It was observed the presence of a statistically significant difference (p=0.0038) about the duration of therapy required to achieve the cytological modifications appropriate to the desired sex, in fact it is much more rapid and powerful testosterone action compared to that estrogen in altering the vaginal environment.

Conclusion.
It can be concluded as in the FtM to change the vaginal cytology are just a few months of hormone therapy with testosterone. Testosterone therapy can be modulated through the observation on vaginal cytology of FtM a framework atrophic and the reduction of Döderlein Bacillus like the cytologic pattern of menopausal women.

Keywords: Transsexualism, Vaginal cytology, Neovagina

Keywords: Transessualismo, Citologia vaginale, Neovagina

Introduction

The concept of sexual identity must always be kept in mind by those who, doctors or psychologists, dealing with the health, not just the sexual as an integral part of the mental well-being of the person. By this point, has made the ‘Gynecological Surgery of Gender Dysphoria, at the OU II of Gynecology and Obstetrics, General Hospital of Bari.

From March 2011 to November 2012 a total of 70 transsexual patients were attended to our Institution. Considering the few Centers which provide care activities in Italy, we wanted to contribute to a systematic data collection, with the consent of each patient and in accordance with the Declaration of Helsinki of 1975.

In these patients to ensure the maintenance of phenotypic sexual conversion, there is a need to carry out a long-term hormonal therapy. There are few data in the literature (13) about possible side effects in the medium and long term. There is therefore the need to perform a follow-up designated for each patient to provide specific therapy to individual needs.

In order to facilitate the reduction of side effects and get a hormonal therapy personalized and effective, has been sought by a supplementary experimental and economically cheaper than the hormone blood chemistry monitoring, in order to verify the adequacy of the dosage of hormone sexual conversion therapy for each of the FTM (Female to Male) and the MtF (Male to Female).

For this purpose, since the vaginal mucosa constitutes the target structure sensitive to the stress hormone, it was considered appropriate to ascertain whether the hormonal vaginal cytology, both in FtM (with persistence of vagina) that in MtF underwent to surgery (Neovagina), may represent a tool to judge the appropriateness of therapy.

Objectives of the study

In the present study, the primary objective was to describe the vaginal/vulvovaginal cytology not only in female transsexuals (MtFs) with Neovagina (inversion technique of the penile skin), but also in FtMs, where surgery has not included the vaginectomia. The secondary objective was to compare the results of cytology is that MtF and FtM with the evaluation of estrogen, with the ultimate aim of assessing whether the cytology may be useful for the follow-up of hormone treatment.

Materials and methods

We enrolled 22 transsexuals to investigate the relationship between serum hormone, hormone dose administered and the degree of cellular vaginal estrogenization.

Of the 22 subjects enrolled, 8 were part of MtF and 14 FtM group.

In the MtF transsexuals group, the neovagina was obtained by inversion of penile skin. In the FTM group, 12 had not yet been operated while practicing hormonal therapy with androgens and only 2 were subjected to implantation of a penile prosthesis with preservation of the vagina, after removal of the uterus and ovaries.

The cytology at the level of the vulva, vagina and cervix for FtMs was performed. For MtF the sampling was limited to the vaginal vault.

Preliminary instructions for cytology showed abstaining from sexual intercourse and the use of vaginal plugs, vaginal hygiene products (such as soaps, lotions, gels, pessaries) for at least three days before the cytology.

It was used the speculum of Collins (10 × 2.5 cm) and in cases of minor compliance, the smaller (10 × 2.0 cm) and still the speculum may be slightly lubricated with a few drops of sterile water to avoid interference with cytology. For both groups we used the Ayre’s spatula, while for FtM (no surgery) has also used the cytobrush.

When the test result is abnormal was performed the PCR, aimed also looking for high-risk human papillomaviruses (HR-HPV), using probes for HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68. For the reading of the cytology of both FtM and MtF the Papanicolaou staining was used.

Since the data in the literature on vulvovaginal cytology and hormonal evaluation (estrogen assessment) of the same are very scarce (47), in our study the degree we correlated the nucleated cells and bacilli Döderlein presence with the effectiveness of hormonal treatment with estrogen for MtF. While a reduction in the percentage of superficial and intermediate cells and bacilli Döderlein suggested a good hormonal therapy with testosterone for FTM.

Statistical Analysis
The distribution of the variables was expressed as means and standard deviations. The data were compared with Fisher exact test and Wilcoxon (rank sum test) for continuous and categorical variables, respectively. It was considered statistically significant p <0.05. All analyzes were performed using SAS statistical package version 9.2 (SAS Institute, Cary, NC).

Results

We detected statistically significant difference (p = 0.0038) about the duration of therapy required to achieve the cytological modifications appropriate to the desired sex, in fact it is much more rapid and powerful testosterone action compared to that of estrogen in altering the vaginal environment (Table 1).

Table 1Table 1
CHARACTERISTICS ANALYSIS BETWEEN THE GROUPS: MTF AND FTM.

In subjects MtF (Figure 1), estrogen therapy is monitored by evaluating the presence of those that are the indices such as the optimal cytology:

  • - presence of nucleated cells with anucleated typical epidermis cells reduction (2/8 MtF 25%);
    Figure 1Figure 1
    Cytology of the neovagina in MtF transsexuals: nucleated squamous cells, Döderlein bacilli and absence of inflammatory reaction.
  • - the detection of Bacilli Döderlein with the presence of anucleated cells (2/8 MtF, 25%); and finally
  • - the absence of neovagina inflammation (7/8 MtF, 87.5%).

For which it is possible to say that 50% of patients had a good degree of estrogen effects with a (neo) vaginal epithelium able to adapt to the new function.

In subjects FtM (Figure 2), for the monitoring of therapy with androgens was evaluated:

  • - the gradual decrease of cellularity (9/14 FtM; 64.3%) (Table 2);
    Figure 2Figure 2
    Vaginal cytology in FtM transsexuals: basal and parabasal cells with hypertrophied nuclei, disappearance of Döderlein bacilli and moderate infiltration of inflammatory cells.
    Table 2Table 2
    CELLULARITY OF CYTOLOGIES.
  • - increased inflammatory cells (9/14 FtM; 64.3%);
  • - the slow atrophy of the epithelium with a prevalence of parabasal, basal and intermediated cells, for which we will see the largest cells and belonging to the lower layers with overall eosinophilia reduction, framework wholly comparable to that of the woman in menopause;
  • - and finally, the Bacilli Döderlein reduction was present in only 2/14 MtF, 14.28%, so we deduce that only these two would require a dosage increasing of testosterone.

Discussion

Both the neovagina in the MtF group that the vaginal epithelium of the original tissue FtM affected by exposure to endogenous and exogenous influences such as hormones and bacteria. In the literature, few studies evaluated the one hand the absence of changes in vaginal tissue and the other modifications of cytology in neovagina (13, 7).

We decided to compare the results of cytology obtained by cytobrush on the vulva and vagina in connection with the use of hormone therapy in FtM and MtF transsexuals and we tried to figure out if the cytology could be useful for the modulation and the consequent tailoring hormonal therapy in transsexual population.

The primary objective of the study was to verify if the neovagina in transsexuals MtF and the vagina in FtM are sensitive to exposure to hormones. The data of our study on the observation of vaginal cytology suggest that androgens have a more powerful effect of estrogen on vaginal epithelium.

In fact, the testosterone requires half the time to change the cytology of the vagina in FtM compared to what happens for the MtF (p=0,0038).

Treatment with testosterone may be the cause of the absence of bacilli Döderlein, the increase of the inflammatory reaction and disruption of cellular differentiation of the vagina in the group FtM (4).

In contrast, estrogens do not induce an inflammatory reaction in the neovagina, but contribute to create a suitable environment for the development of bacilli Döderlein (2 of 8 MtF 25%), with subsequent nucleated cells disappearance and relative reduction anucleated cells. In fact, 30.6% of neovagine presents cellular inflammation with squamous nucleated cells not correlated to hormone therapy, but to the sexual habits of these patients.

In our sampling the adequacy of cytology was judging based on the cellularity of each slide. According to the classification of Bethesda cytological sampling is unsatisfactory when ≤ 5000 squamous cells are present and / or ≥ 75% of squamous cells are obscured by inflammatory cells or red blood cells.

Following this parameter, the level of the neovagina obtained by inversion of penile skin, while there is always a certain amount of cellular debris and sebum secreted none of the cell smears of neovagina was judged inappropriate based on the number of nucleated squamous cells taken from neovagina.

Conclusions

It can be concluded as in the FtM to change the vaginal cytology are just a few months of hormone therapy with testosterone (of course not forgetting the serology).

Testosterone therapy can be modulated through the observation on vaginal cytology of FtM a framework atrophic and the reduction of Döderlein Bacilli like the cytological pattern of menopausal women.

While in the MtF group, we observe a statistically significant difference, relative to the speed of action for the obtaining cytological changes: in fact, estrogen require approximately twice the time, compared to androgens in FtM, to change the cytology and obtain similar characteristics to those of biological women, such as the rate of nucleated cells and the extent of the presence of Döderlein Bacilli.

Even here the hormonal cytodiagnosis results to be of aid for obtaining the correct estrogen degree of neovagina.

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