Common Causes of Vaginal Discharge

When a female has symptoms of abnormal vaginal discharge & odor, vaginal pain & itchiness, and/or burning sensation when passing urine, she may be infected by one of these organisms: bacteria, fungus or protozoa parasite.

Bacteria infection in the vagina is called bacterial vaginosis. It is most commonly caused by Gardnerella vaginosis, or less commonly by Bacteroides, Fusobacterium, Ureaplasma, Mycoplasma etc, when the balance of good & bad bacteria in the vagina is disrupted. Besides vaginal irritation, bacterial vaginosis typically produces fishy-smell thin gray/white homogenous vaginal discharge which is adherent to the vaginal wall. It is not considered as a sexually transmitted disease as sexually inactive female can still be infected. However, the risk of infection increases with multiple sexual partners and douching.

      Bacterial vaginosis: white thin discharge, with fishy smell

Vaginal candidiasis is a fungal infection in vagina usually caused by yeast Candida albicans. Certain amount of yeast live in the normal vaginal tract with other bacteria. When the amount of yeast overgrow other bacterias, such as when broad-spectrum antibiotics are taken or poor immunity, vaginal candidiasis can occur. The vaginal discharge is white and curd-like but lack odor. It is quite common and is not considered a sexually transmitted disease.

      Candidiasis: White thick curd-like discharge

Trichominiasis is caused by infection of a protozoa called Trichomonas vaginalis. It typically produces greenish & yellowish foul-smelling vaginal discharge and causes significant pain during sexual intercourse. It is a sexually transmitted disease and can affect male as well. It is said that 70% of infected female have no symptoms though.

      Strawberry Cervix: typical in Trichomoniasis

All three types of infection can occur during pregnancy, and are known to increase the risk of preterm labour and low birth weight. To know what type of organism it is, vaginal fluid/discharge can be taken and study under a microscope. 

Bacterial vaginosis is the commonest cause of vaginitis, followed by candidiasis and trichomoniasis. Sometimes it is not easy to differentiate them without lab tests.

These infection can be treated when the type of culprit is identified or suspected:

• Bacterial vaginosis: 
• oral metronidazole 500mg twice a day for 7 days OR
• oral metronidazole 2g as single dose OR
• oral clindamycin 300mg twice a day for 7 days OR
• topical clindamycin (cream/suppository) at bedtime for 3 nights

• Vaginal candidiasis: all types of anti-fungal (oral OR topical - in the vagina)
• oral fluconazole 150mg single dose OR
• oral itraconazole 200mg twice a day for one day OR
• anti-fungal cream/suppository at bedtime usually for 3-7 days

• Trichomoniasis: 
• oral metronidazole 500mg twice a day for 7 days OR
• oral metronidazole 2g as single dose

Most infection can recur after treatment. Sometimes sexual partners have to be treated as well. For treatment during pregnancy, please consult your doctor.

Abnormal Menstrual Bleeding

An ideal menstrual cycle lasts for 28 days, with the first day calculated from the onset of menstrual bleeding and ovulation is at day-14 of the cycle. Normal menstrual cycle has a mean interval of 21-35 days, with a duration of 2-7 days and 30-80ml menstrual bleeding. 

Anything outside these range may be viewed as abnormal. These can be:

• menorrhagia: excessive (>80ml/day) or prolonged (>7 days) bleeding
• polymenorrhea: menstrual bleeding interval <21 days
• oligomenorrhea: menstrual bleeding interval >35 days
• metrorrhagia: irregular and more frequent menstrual bleeding
• metromenorrhagia: irregular, more frequent and excessive bleeding
• dysmenorrhea: excessive menses pain
• amenorrhea: absent of menstrual bleeding for >6 months
• intermenstrual bleeding: bleeding/spotting in between regular menstrual cycles
• postmenopausal bleeding: bleeding after >6 months menopause

Important causes of abnormal menstrual bleeding that need to be ruled out:

• Pregnancy and its related complication

• Gynecological pathology

• Benign lesion
• uterine fibroid/polyp
• cervical polyp
• adenomyosis
• polycystic ovary syndrome

• Non-benign lesion
• uterine cancer
• ovarian cancer
• cervical cancer
• vaginal cancer
• endometrial cancer
• endometrial hyperplasia

• Pelvic inflammatory disease
• cervicitis
• salpingitis
• endometritis

• Trauma
• cervix
• vagina
• vulva

• Endocrine disorders
• Hyperthyroidism
• Hypothyroidism
• Hyperprolactin

• Blood clotting disorders
• Thrombocytopenia
• Von-Willebrand's disease
• Coagulopathy

• Iatrogenic
• Oral contraceptive pills
• Intrauterine contraceptive devices
• Medication
• anti-coagulants

• Dysfunctional uterine bleeding (diagnosis of exclusion in the absence of organic disease)
• Stress / Excessive exercise etc.

Dysfunctional uterine bleeding is more common in the extremes of reproductive age, which are the first 2 years after the onset of menses (menarche) and a few years before the termination of menses (menopause). About 90% of the abnormal bleeding is anovulatory, in which there is no ovulation within the cycle because of certain disruption in the hypothalamus-pituitary-ovary axis.

Important investigations for abnormal uterine bleeding

• pregnancy test
• pelvis ultrasound scan
• blood test: platelet, coagulation, thyroid function, prolactin
• hysteroscopy
• endometrial sampling/biopsy

     Endometrial biopsy

The treatment depends on the underlying cause of abnormal bleeding. If no organic disease can be found (dysfunctional uterine bleeding), treatment available includes:

• Tranexemic acid
• NSAIDs
• Danazol (ethisterone)
• GnRH agonists
• Combined oral contraceptive pills
• Progesterone only pills
• Intrauterine devices with progesterone
• Endometrial ablation (if future pregnancy not wanted)
• Hysterectomy (if future pregnancy not wanted)

Pap smear: When to start and What to expect?

Pap smear/test is a screening test used to detect early changes in cervical cancer. "Pap" is named after Dr George Papanicolaou. Before the cells in the cervix turn into cancer cells, they undergo a few pre-cancerous changes. If these changes can be picked up early, then treatment can be given and cervical cancer can be prevented.

The precancerous cell changes are called dysplasia or cervical intraepithelial neoplasia (CIN). CIN can be divided into mild (CIN 1), moderate (CIN 2) and severe (CIN 3). CIN 1 usually can go away on its own but it still can progress to CIN 2/3. CIN 2 and 3 are more serious and need further test.

Through Pap smear, a brush is used to sample cells around the cervix and viewed under a microscope. Liquid-based cytology is more accurate compared to the conventional Pap smear. It is best to do pap smear between 10-20 days after the first day of menstruation.

Pap smear schedule:

Start: Age 21, or 3 years after first vaginal intercourse

Stop: Age 70, and with 3 consecutive negative tests, and no abnormal test in prior 10 years.

Post total hysterectomy: discontinue if benign reasons & no high grade CIN

Interval:

• Conventional pap test: annually
• Liquid-based cytology (LC): every 2 years
• LC with negative HPV test: every 3 years

•  For conventional and LC, if age >= 30 years old with 3 consecutive negative Pap smears, can repeat in 2-3 years.

 Updated Oct 2012

The American Congress of Obstetricians and Gynecologists has updated its 2009 practice bulletin on cervical cancer screening; its guidelines generally align with those released earlier this year (2012) by the U.S. Preventive Services Task Force, the American Cancer Society, and other groups.

Among the recommendations for routine screening:

• Women under age 21 should not be screened, regardless of behavioral risk factors. 
• For those aged 21 to 29, cytology alone should be performed every 3 years.
• For women aged 30 to 65, cytology plus human papillomavirus co-testing every 5 years is preferred; however, cytology alone every 3 years is acceptable.
• Women should not be screened after age 65 provided they've previously had sufficient negative screening results and no history of cervical intraepithelial neoplasia grade 2 or higher.
• More frequent screening may be required for women who have a history of cervical cancer or CIN2 or higher, who are immunocompromised (including HIV-infected), or who were exposed to diethylstilbestrol in utero.

    Pap smear

The Bethesda System is often used to interpret pap smear's result. In this system, the term squamous intraepithelial lesion (SIL) is used instead of CIN. 

Pap smear result can either be:

• Negative (normal)

• Atypical squamous cells of undetermined significance (ASC-US)
• most common result
• usually indicate HPV infection which may normalize if infection is cleared

• Squamous intraepithelial lesion - low grade (LSIL)
• equivalent to mild dysplasia (CIN 1)
• may goes away without treatment
• may indicate mild precancerous change

• Squamous intraepithelial lesion - high grade (HSIL)
• more likely to progress to cancer
• equivalent to CIN 2,3 and carcinoma in-situ

• Atypical squamous cells, cannot exclude HSIL (ASC-H)
• not clearly HSIL but could be

• Atypical glandular cells  (AGC)
• suggest precancer cells

• Cancer
• abnormal cells may have spread deeper

Abnormal Pap smear results will require further tests, either repeat Pap smear, do HPV test or colposcopy. Biopsy or other minor intervention such as conization, cryocauterization, laser therapy, large-loop excision of the transformation zone or endometiral sampling may be needed.

      Follow up test for abnormal pap smear result

HPV and Cervical Cancer

Human Papillomavirus (HPV) is a common sexually transmitted infection. If you are sexually active, there is a 50% chance that you have already infected with HPV at some point of time. Most of the time HPV infection will not produce any symptoms and our body immune system can cure it by itself within 2 years time without any treatment (median 8 months). However, some infected people may have genital warts and for female, it may lead to pre-cancerous changes in the cervix. The pre-cancerous changes need further monitoring and possibly treatment.

           Human Papillomavirus

HPV has been widely discussed now because of its link to cervical cancer, though the risk is very small. Besides, HPV is also related to other types of cancer around genital area such as vagina, vulva, penis and anus. 

There are more than 100 types of different HPVs, however, only about 40 has clinical significance to human. Base on their risk to cause cancer, they can be divided into "high risk" type and "low risk" type. HPV type 16 and 18 are the most well known high risk type and both are associated with almost 70% of cervical cancer.

HPVs can infect both male and female equally. It can be transmitted from a person to another through direct contact during sexual intercourse. So if you start to have sex at early age, have multiple sexual partners or if your partner has multiple sexual partners, your risk of getting HPV infection is higher.

Most HPV infection is transient, but about 10% of women may have persistent infection. If the persistent HPV type is HPV 16/18, then the risk of developing cervical pre-cancerous changes is higher. It may progress to cervical cancer if left untreated.

Since long time ago Pap smear has been available as a screening tool for cervical cancer in female. Now Pap smear is still the most important screening test that save lives. Its accuracy is improved with the new liquid base cytology test, which is better than the conventional "scrape and spread on slide" test.

Not long ago, HPV DNA test is recommended as as "add-on" to Pap smear to further help the decision making for doctors in patients with abnormal pap smear result. HPV DNA test is not recommended routinely for women <30 years old unless the Pap smear shows abnormality. It cannot substitute Pap smear as the main cervical cancer screening tool. If the HPV DNA test is positive for high risk HPV type in a patient with "borderline" Pap smear result, then it may prompt further investigation.

      

    Changes in cervix caused by HPVs

HPV infection can be prevented through vaccine. Currently there are 2 types of vaccines available: Gardasil (HPV 6, 11, 16, 18) and Cevarix (HPV 16, 18). HPV 16 & 18 are the most common high risk HPV that account for almost 70% of cervical cancer. HPV 6 & 11 are low risk HPV that can only lead to genital warts.

These vaccines are given in 3 separate intramuscular doses (0, 1-2, 6 months apart). They are found to be 100% effective in preventing pre-cancerous cervix lesion caused by HPV 16 & 18. Thus it should be able to prevent 70% of cervical cancer (as HPV 16 & 18 cause 70% of cervical cancer). It is not 100% prevention from cervical cancer. There are other types of high risk HPVs and many other possible causes for cervical cancer. So Pap smear is still mandatory even after you have received Gardasil or Cervarix vaccination.

Vaccination is best given to girls/women before they are infected with HPV 16 & 18, or in other words, before having their first sex. It can be given as early as 9 years old up to over 40 years old. However, the earlier the better it is.

 

Raised CA-125: What are the Causes?

CA-125 is a protein found mostly in certain types of cancer cells. CA stands for cancer antigen and CA-125 is known as a tumour-marker especially for ovarian cancer.

CA-125 is traditionally done to measure the success of ovarian cancer treatment or when a pelvic mass is found. It is not suggested to be used as a screening test for ovarian cancer because it is not accurate with high probability of false positive and false negative results. CA-125 can be high in certain cancers other than ovarian cancer, and in other non-cancerous condition as well.

     Female reproductive organs

Here is a list of conditions which can cause a raised CA-125:

Cancer

• Ovary
• Uterus/endometrium
• Fallopian tube
• Breast
• Pancreas
• Liver
• Lungs
• Bowel
• Bladder
• Cancer with peritoneum involvement

Non-cancer (gynecological)

• Benign ovarian cyst
• Endometriosis
• Fibroid
• Pelvic inflammatory disease
• Pregnancy (first trimester)
• Menstruation

Non-cancer (non-gynecological)

• Pancreatitis
• Liver cirrhosis/failure
• Renal failure
• Nephrotic syndrome

The normal value of CA-125 is <35 u/ml. If you have a level higher than 35, then you should have an ultrasound scan to check your ovaries and uterus. Your doctor will take relevant history from you and examine you thoroughly. If nothing can be found, usually you are only required to repeat the test at an interval and follow up with the doctor.

If a pelvic/ovarian mass is found, depends on its characteristic, a surgery may be required to confirm whether it is cancerous or not. Sometimes it can just be a benign (non-cancerous) ovarian tumour or endometriod cyst.

However, not everyone with confirmed ovarian cancer will have an abnormal CA-125 results. Only about 50% of stage I ovarian cancer patients have raised CA-125. For stage II, III, IV ovarian cancer patients, 80% will have raised CA-125 while for the rest of 20% of these patients, their CA-125 level remain normal.

A study done in 1999 by IJ Jacobs screen about 10,000 post-menopausal women over 45 years old using the CA-125 test alone. Results of this study showed a false positive rate of about 80%. (only 20% of these women with abnormal CA-125 had ovarian cancer)

Another study screened 11,000 post-menopausal women over 45 years old with CA-125. As a result, 468 of them were found to have raised CA-125 and ultrasound scan were done. Of these 468 women, 29 underwent surgical procedure and noted:

• 6 had ovarian cancer (1.3% - 6 out of 468)
• 2 had adenocarcinoma of unknown origin
• 14 had benign tumour
• 4 had fibroids
• 3 had no abnormality

We can see that the false positive rate of CA-125 test varies from different studies, but we know that the chance of ovarian cancer with a raised CA-125 is not very high. However, this should not be the reason for us to ignore the positive result. To improve the accuracy of the test, a serial CA-125 tests should be done to see the trend, and ultrasound scan should be performed.

Ovarian Cysts: When to worry

With the increasing use of the ultrasound scan for screening purpose, more cases of ovarian cyst have been diagnosed than ever. Should you be worried if you have one, or two?

In more than 95% of time, ovarian cysts, which are just sacs filled with fluid, are harmless or not cancerous. It usually produces no symptoms, but may cause pain at the lower abdomen if the cyst burst, bleed or twist.

Normal ovaries are filled with many small cysts (usually <2.5cm – physiological cysts). During menstrual cycle, when an egg gradually mature in a cyst, the cyst will increase in size to become a follicle. When the egg is released, the follicle will turn into corpus luteum, which will then shrink in size gradually. However, sometimes this whole process does not occur in a perfect way. When the egg fail to get out from the follicle, follicular cyst will form. The size of follicular cyst is >2.5cm and sometimes can even reach 20cm. In other scenario, when the egg is released but the corpus luteum fail to shrink, a corpus luteum cyst will form. These 2 types of ovarian cysts are called functional cysts as they are part of the normal process of menstruation. They are generally harmless and will shrink in size after a few menstrual cycles.

Other non-functional but benign ovarian cysts include dermoid cyst, endometrioid cyst and cystadenoma. Dermoid cyst, or cystic teratoma is a benign tumour which contains various types of body tissues inside such as hair, bone, skin etc. This may sound scary but it is not cancer. Endometrioid cyst forms when menses blood flow backwards to the ovaries and collect there. It is also called a “chocolate cyst” because the cyst is filled with chocolate-like blood. Cystadenoma does not form from an ovarian follicles but from other part of the ovary. It is also benign though can be very large.

    Dermoid cyst with hair inside

    Chocolate cyst

To make it less complicated, ovarian cyst can be divided as follows:

• Benign (>95%)
  • Functional (follicular cyst, corpus luteum cyst)
  • Non-functional (dermoid cyst, endometrioid cyst, cystadenoma, PCOS)
• Malignant (cancerous)

From ultrasound, we can know the "growth" in the ovary is either cyst or solid. Solid growth is not good news. If it is a cyst, it can be a simple or a complex cyst. Simple cyst means that the cyst appears all black in an ultrasound image. It will be a complex cyst if there are white lines/dots inside. Simple cyst, like what it sounds, is usually functional cyst and harmless. Complex cyst can be either cancer or non-cancer and require closer monitoring or further test. Dermoid & chocolate cysts usually appear as complex cysts.

    Simple ovarian cyst: usually harmless irrespective of size

Any ovarian cyst <2.5cm is normal (physiological). Cysts between 2.5-5cm are most likely functional cysts. Just repeat the ultrasound scan in 3 months time to see how it changes. Functional cysts will usually shrink in size or disappear in less than 3 menstrual cycles. However, if the size increases to >5cm, it may be non-functional cysts, which are still benign but need follow up scan. For ovarian cysts >10cm, intervention or surgery may be considered. Sometimes CT scan may be needed to further evaluate a complex cyst. The presence of endometrioid cyst even of any sizes may be harder to manage as it is usually associated with severe menses pain and infertility.

Ovarian cyst can occur in all ages. It is common in child-bearing age as the ovaries are forming follicles and corpus luteum in every menstrual cycle. However, if it is found in post-menopausal women, more attention need to be given as the risk of cancer increases since there will be no more functional cyst there.

Nevertheless, benign cysts can get bleeding, ruptured, twisted or infected. If you are worry or unsure, please consult a gynaecologist.