Cytological Change in Cervical Smears Associated With Contracepti
Gynecology & Obstetrics

Gynecology & Obstetrics
Open Access

ISSN: 2161-0932

Research Article - (2018) Volume 8, Issue 9

Cytological Change in Cervical Smears Associated With Contraceptive (Hormonal and IUCDs) Use In Women Visiting Cytology Unit of Korle-Bu Teaching Hospital for Routine Cervical Screening

Ama Afrah*, Yao Tettey and Richard Kwesi Gyasi
Department of Pathology, College of Health Sciences, University of Ghana, Ghana
*Corresponding Author: Ama Afrah, Department of Pathology, College of Health Sciences, University of Ghana School of Biomedical and Allied Health Sciences Ghana, Ghana, Tel: 457851891 Email:


Contraception traces its roots back to the old testament in the bible: ‘’And Onan knew that the seed should not be his; and it came to pass, when he went in unto his brother’s wife, that he spilled it on the ground, lest that he should give seed to his brother’’ Onan then practised coitus interruptus.

Sustainable Development Goal (SDG) proposes that by the end of year 2030 the world should be transformed by empowering women and girls through economic, social and environmental development. Couples who plan their family are happier as compared to couples with unplanned family suffer depression and anxiety.

Contraception narrows gender pay gap and increases woman earning power. Children born to poor couples have poor health, lives in dangerous neighborhood and have higher rates of delayed academic development. National Cancer Institute states that there are several evidences confirming the increased in relative risk by 7% of cervical cancer when women are on hormonal contraceptives with risk declining when the contraception was halted. Oral contraceptives and cancer risk.

Use of hormonal contraceptives for more than 10 years could be a co-factor for the development 4 fold risk cervical cancer in women who are positive for genital HPV infection. In a study using mice models, genital HPV infection induces squamous carcinogenesis of cervical transformation zone but different doses of oestrogen for the same length of time resulted in squamous carcinoma of vagina, transvaginal or cervical transformation zone.

In IUCD users, prevalence of pelvic Antinomies infection with hydronephrosis in chronic infections as well as inflammation with extensive metaplasia had been reported. Bacterial vaginosis and Candida albican are associated with IUCD use.

In comparing parous women on oral hormonal contraceptives and parous women on IUCD, prevalence of carcinoma in situ and dysplasia was high in the former.

Study Design

This was a prospective study. Using stratified random sampling method, women were recruited into the study.

Study site

The study was done in the department of pathology, University of Ghana medical school (UGMS), Korle-bu Teaching hospital (KBTH). The department has 4 units; cytology, histology, immunology and mortuary. The department undertakes both retrospective and prospective cancer researches [3].

Subjects/ target population

The study population was women visiting the cytology unit of Korle-bu teaching hospital for routine Pap smear examination.

Inclusion Criteria

Study cases

Women between the ages of 20-49 years on injectable hormonal contraceptives and IUCD who agreed to partake in the study.


Women without any history of contraceptive use between ages of 20-49 years.

Exclusion Criteria

Women below 20 years and women above 49 years who are on contraceptives.

Sample size

Seventy five women were recruited to do the study.

Informed Consent

The objectives of the study were explained to every woman and those who were willing to participate in the study signed and informed consent and filled a questionnaire.

Ethical Issues

The ethical and review committee of the College of Health Sciences, University of Ghana gave approval for the study after reviewing the proposal.

Sample Preparation/Pap Smear

The procedure of taking of Pap smear was explained to study samples.

Using sterile kits for each women, cells were picked from 3 spots of the female reproductive tract; ectocervix, end cervix/transformation zone and upper fornix of vagina. A speculum was used to open up the vagina to assess the cervix. One part of a spatula that is shaped like the lip of the cervix was used to pick cells from the ectocervix by rotating it at 360° and smeared on a side (1st pool) labeled with the study subject peculiar research number. Moving another 360°, the cytobrush was used to pick cells from transformation zone and smeared (2nd pool) and finally, the flat side of the spatula was used to pick cells from the upper fornix of the vagina (3rd pool) to prepare smears and fixed wet with polyethylene glycol (PEG).

Papanicoulaou Staining Technique

Labelled slides were placed in 95% ethanol for at least 5 minutes to remove carbo wax and hydrated using descending grades of ethanol (3 changes) to water. Nucleus in hydrated smears were then stained with hematoxylin for 4minutes and ‘blued’ using running tap water as a substitute monitoring bluing microscopically. The smears were dehydrated using ascending grades of ethanol to 95% and subsequently keratin was stained with Orange ‘G’ in cytoplasm.

Excess stain was removed with 95% ethanol and smears finally stained in Eosin Azzure/Eosin Alcohol, cleared and mounted using DPX mountant and coverslips (Table 1). The stained slides were examined with Olympus microscope model CX41 first screening smears with 10X and confirming diagnosis with 40X.

Age (years) Frequency      Percentage (%)
20-29 14 18.6
30-39 32 51.2
40-49 29 30.2
Total 75 100

Table 1: Age distribution patients recruited into the study.


There was no pre-screening (Pap smear) to find out the suitability of method of contraception, the only thing that mattered that point in time was prevention of unwanted pregnancy. Out of the 75 women 66.7% were on hormonal contraceptives, 33.3% were using IUCD. The mean age of women using contraceptives did 35.5 years constitute 44.4% of the study samples. Most (40%) of women on IUCD had worn them between 6-10 years whilst the women on hormonal had duration of use between 1-5 years (Table 2).

Control Iucd Injectables
Frequency Percentage Frequency Percentage Frequency Percentage
Dordelein cytolysis 2 8 3 12 2 8
Actinomyces - 0 1 4 - 0
Bacterial vaginosis 1 4 6 24 5 20
Inflammatory change 2 8 5 20 2 8
Absence of TZ components 2 8 2 8 5 20
Endocervical vacuolation - 0 5 20 1 4
Atrophic change 4 16 - 0 7 28
Endometrial cells - 0 3 12 1 4
CIN I/HPV - 0 - 0 2 8
CIN II - 0 - 0 - 0
CIN III - 0 - 0 - 0
Invasive cancer - 0 - 0 - 0
Negative 14 56 - 0    
Total number 25 100 25 100 25 100

Table 2: Cytological findings in cervical pap for study subjects and controls.

The long duration of use for IUCD was due to the fact that once worn, there was no need for patient compliance.

Parity: majority of women on IUCD was 3 children and majority of women injectable hormonal contraceptives had 4 children in Figure 1.


Figure 1: Cytological finding in cervical pap for study subjects.


In the developed world, prescreening is done to know which method of contraception was suitable for a women Long use of hormonal based contraceptives is strongly associated with cervical cancer. Dordelein cytolysis (DC): DC was high in women using injectable hormonal (32%) than IUDs (12%). Under exogenous progesterone stimulation as is the case with hormonal contraceptives, there is inhibition of maturation of the full squamous epithelium; squamous cells mature to just the intermediate cell level. The normal flora of the vagina is made up of a myriad of microorganism of which Dordelein is one. Alteration in acidic pH towards basic due to prolonged progesterone stimulation causes overgrowth of Dordelein bacilli that feed on abundant glycogen in the cytoplasm of intermediate cells, normal appearing nuclei then float.

Bacterial Vaginosis (BV)

BV was high in IUCD users than injectable hormonal contraceptives because the IUCD which is fitted in the endometrial has a microfilament string attached to it. The string protrudes through the cervix and this serves as a conduit for bacteria to migrate through its protected interstices and into the endometrial cavity to cause infection and inflammation (endometriosis). Persistent bacterial vaginosis leads to Pelvic Inflammatory Diseases (PID). An infection while using an IUCD can cause tubal infertility, peritonitis, and liver damage. There is the possibility of the strings of IUCD to irritate the cervix and predispose the user to septicemia when bacteria enter the blood stream. Secondly if insertion of IUCD is not done aseptically can introduce bacteria into the female genital tract to cause bacterial vaginosis. Since women wearing IUCD are protected against pregnancy, they are unlikely to use any barrier method of protection so they are easily prone to sexually transmitted bacterial infection. Bacterial vaginosis in injectable hormonal users result in change in leucocyte population reflecting alteration in local immunity hence the female genital tract is prone to microbial infections either sexually or opportunistically as well as peritonitis.

Candida albican

Among users of injectable hormonal contraceptives, 16% was infected for Candida albicans. No IUCD user was infected because high vaginal hygiene was maintained. During administration of steroid hormone there is alteration in glucose metabolism, immunity, vaginal flora and pH so the female genital tract is subjected to Candida albicans infection. Candida albicans proliferates by consuming and fermenting sucrose and other simple sugars with acetaldehyde as a toxic by product which interferes with cellular energy production by depleting acetyl coenzyme A and vitamin B3. Candida albicans when it gets into the liver impairs methylation of proteins. Proliferation of Candida albicans can results in cystitis due to the proximity of bladder to vagina. Candida albicans infection of the cervix can lead to infertility in women due to tubal blockage.

Absence of Transformation Zone Components

There were reported cases of ‘no transformation zone components’ in injectable hormonal contraceptive users (24%) than IUCD users (8) as compared to controls (4%). In hormonal contraceptive users, suppression of estrogen release due to anovulation under exogenous progesterone administration makes the external of the cervix invaginator making the transformation zone inaccessible during Pap smear sampling. The transformation zone is a region of epithelial instability therefore the likelihood of any neoplasia beginning so if cells from that region are not represented in a Pap smear diagnosis cannot be made even if the smear is negative.

Benign Cellular Change

Nuclei enlargement, inflammatory change, Endocardial vacuolation, Atrophic change.

Nuclei Enlargement/ Inflammatory Change (20%)

The cervical vaginal epithelium is subjected to a lot of stimuli including vitamin. Vitamins C and B12 as well as foliate deficiencies are associated with the use of hormonal contraceptives since they interfere with metabolism of these vitamins around the cervix.

These vitamins prevent or retard progression of cervical intraepithelial dysplasia that may exist locally to carcinoma hence deficiency can lead to rapid progression of existing dysplasia to carcinoma.

Secondly in the absence of existing cervical lesions, lack of these vitamins may distort the nuclei of cervical cell which can mimic carcinoma. Vitamin B12 and foliate are coenzymes for DNA synthesis hence deficiency of these vitamins will lead to thymine deficiency which mimic radiation DNA injury.

Inflammatory change in epithelial cells admixed many inflammatory polymorphs in IUCD users was high (20%) as compared to injectable hormonal contraceptive users (8%). The spermotoxic effect of IUCD is inflammatory. IUCD is a foreign body so on insertion; an inflammatory reaction is induced in the endometrium, which phagocytic leucocytes to engulf sperms and ova. Epithelial cells imbibe water so there is nuclei/cytoplasm enlargement making them hypochromic when stained. The overall enlargement and prominent nucleolus of an epithelial cell may cause them to be mistaken for malignancy [5,6].

Endocardial Vacillation

Vacillation was present in endocardial cells in smears of IUCD users (20%). Endo- cervical glandular cells are mucus secretory in nature forming vacuoles. With the insertion of IUCD device, the end cervical cells undergo metaplasia with neutrophil infiltration pushing the nuclei to the periphery making the nuclei eccentric. In cases of hypervacuolation, endocardial cells mimic adenocarcinoma.

Atrophic Change

Twenty eight percent of women wearing IUCD had parabasal cell pattern in smears which was not consistent with their ages.


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Citation: Afrah A, Tettey Y, Gyasi RK (2018) Cytological Change in Cervical Smears Associated With Contraceptive (Hormonal and IUCDs) Use In Women Visiting Cytology Unit of Korle-Bu Teaching Hospital for Routine Cervical Screening. Gynecol Obstet (Sunnyvale) 8: 485.

Copyright: © 2018 Afrah A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.