BACKGROUND. myriad of complications that have physiological and psychological effects.

Transcription

1 BACKGROUND Gynaecological morbidity is a major socio-economic and medical problem with myriad of complications that have physiological and psychological effects. Approximately three-fourth of the women in any population reported the symptoms of at least one of the gynaecological morbidity. RTI and menstrual disorders are the two conditions which form the major component of the gynaecological morbidity. 2.1: Reproductive Tract Infections: The global burden of RTI is enormous and of a major public health concern, particularly in developing countries where RTI are endemic. 9 RTI, excluding Human Immunodeficiency Virus (HIV) constitute the second major cause of disease burden (after maternity related causes) in young adult women in developing countries. 10 In community based studies conducted in India, prevalence of RTI is reported to be 55-61%. 10 RTI's cover three types of infections: 11, Sexually Transmitted Infections (STI) 2. Infections that result from overgrowth of organisms normally present in the reproductive tract 3. Infections associated with medical procedures including abortion and insertion of intra uterine devices. 6

2 Female RTI usually originate in the lower genital tract as VVS or cervicitis and may produce symptoms such as abnormal vaginal discharge, genital pain, itching and burning micturition or sometimes asymptomatic. Vaginitis or VVS is the most frequent gynecological diagnosis, encountered by physicians who provide primary care to women. Although vaginal discharge was the most perceived symptom of RTI's (Vaginal discharge 57.7% Vulval itching 54.0%) only two third of them are diagnosed to have vaginal infection. 13 The three most common types of vaginitis which comprises 90% of vaginitis 14 are: Bacterial vaginosis (BV) (26%) Candida vaginalis (CV) (14%) Trichomona vaginalis (TV) (8%) 2.1.1: Bacterial Vaginosis (BV): BV is the most common vaginal infection, responsible for 40-50% of infections. 15 It is due to microbial imbalance of the vaginal ecosystem. When there is depletion of the normally dominant hydrogen peroxide-producing lactobacilli, there is overgrowth of certain anaerobic and aerobic organisms which are normally present in the reproductive tract. Most commonly detected organisms in BV are Gardnerella vaginalis, Prevotella spps., Mobiluncus spps., Mycoplasma hominis, and most recently, Atopobium vaginale. 16 Atopobium vaginale is an anaerobic organism that has been 17, 18 linked to a higher risk for preterm labor and recurrent bacterial vaginosis. 7

3 Symptomatic patients with BV typically present with a discharge having characteristic fishy odor which is due to overproduction of aromatic amines and sometimes patients complain of pruritus and vaginal burning. 15 BV may be asymptomatic in up to 34-90% of patients. 19 The importance of BV transcends its vaginal manifestations. BV has adverse effect on pregnancy outcome such as abortion, preterm labor, premature rupture of membranes, chorioamnionitis, amniotic fluid infection, postpartum endometritis, postcaesarean / post-delivery endometritis, and neonatal sepsis. 20, 21 In the non-pregnant patients, BV has been associated with PID, muco-purulent cervicitis, vaginal cuff cellulitis following hysterectomy, and post-abortal infection. 22, 23 In addition, there is mounting evidence that BV is a risk factor for (HIV) infection. 15 Diagnosis of BV: The diagnosis of BV is usually made by fulfillment of the Amsel 24 criteria or, less commonly, on the basis of Gram stain of the vaginal discharge 25. The Amsel criteria: Patient should meet 3 of the 4 following clinical criteria: Thin, milky, homogeneous, adherent discharge, Vaginal ph of > 4.5, Positive whiff test (detection of an amine-fishy odor when 10% KOH is mixed with vaginal secretions) 21, 22 Clue cells on saline wet mount (> 20% of vaginal epithelial cells). 8

4 The gold standard for diagnosing BV in research settings is, Gram-stained vaginal smears (Nungent score) 25, 26 There are quick newer point-to-care tests which measure vaginal ph and detect aromatic amines. 27 Treatment: The standard treatment for BV is metronidazole (Table ). 27 Although other treatments have been shown to have approximately equivalent efficacy, these are associated with higher recurrence rates. TABLE NO : Recommended Treatments for BV: 27 Drug Dosage Adverse effects Metronidazole tablets *Metronidazole 0.75% gel *Clindamycin 2% vaginal cream *Metronidazole tablets *Tinidazole tablets Clindamycin tablets *Clindamycin ovules Recommended regimens 500 mg orally twice daily for 7 days **250 mg three times daily for 7 days 5 g intra-vaginally once daily for 5 days 5 g intra-vaginally once daily at bedtime for 7 days Alternative regimens 2 g orally in a single dose 1 g twice daily for two days or 500 mg twice daily for 5 days 300 mg orally twice daily for 7 days **300 mg twice daily for 7 days 100 g intravaginally once daily at bedtime Teratogenecity during 1 st trimester for 3 days *Insufficient data to support use of these regimens during pregnancy. ** Dosage during pregnancy. Nausea, vomiting, dizziness, loss of appetite Same as above 9

5 2.1.2: Candida Vaginalis CV is the second most common cause of vaginal infections. 10 It is caused by Candida albicans in 70% - 90% of cases. Predisposing factors for candidiasis are pregnancy, broad-spectrum antibiotic use, inadequately controlled diabetes mellitus, and HIV infection. 29 The Center for Disease Control and Prevention (CDC), ( , 29 treatment guidelines) has classified CV as either uncomplicated or complicated. TABLE No : Classification of Vulvo-vaginal Candidiasis: 27 Uncomplicated Complicated Sporadic or Recurrent infection infrequent infection Mild-to-moderate Severe infection infection Candida albicans as Infection with Candida species other than C. albicans likely cause Man without Woman with uncontrolled diabetes mellitus, immunosuppression immunosuppression, or debilitation; pregnant woman (Adapted from: Sexually transmitted diseases treatment guideline Center for Disease Control and Prevention MMWR Recomm Rep 2000; 51(RR-6):1 80.) 10

6 Diagnosis of Candida Vaginalis: In most of the patients with CV, vaginal ph is mildly acidic. 10, 27 Examination of the smear, should be done after providing adequate time for KOH to dissolve the keratin elements in the smear. The presence of pseudohyphae confirms the diagnosis of CV, most commonly with C albicans (Figure 5). This is present in 38-83% of cases. 10 In patients with smear negative with KOH prep., isolation of the Candida can be done by culturing the sample on Sabouraud s medium. There is a DNA-probe test which detects presence of C. albicans. Treatment: In uncomplicated infections first- line therapies are topical antifungal agents (Table No ) which include polyene antifungal agents (eg.mycostatin) or first or second generation imidazole agents (eg. clotrimazole, butoconazole) and a triazole agent (teraconazole). 11

7 Table No : Treatment of Candida vaginalis: 29, 30 Intravaginal Agents: Clotrimazole 1% cream 5gm intravaginally for 7-14 days.recurrence prolong treatment for 2 wks. Clotrimazole 100 mg vaginal tablet/ suppo. one tab for 7 days or 2 tabs for 3 days Butoconazole cream 2% 5 gm Intravaginally for 3 days 100 mg suppo. 1 suppo. For 7 days or 200 mg 1 suppo. For 3 days or 1200 mg for 1 day. Nystatin units vaginal tablet, 1 tablet for 14 days Triconazole 6.5% ointment 5 gm intravginally single application Oral Agents: Tab. Fluconazole 150 mg single dose. Recurrence: 150 mg two doses three days apart Ketaconazole: 400 mg daily for 2 weeks followed by 100 mg daily for 6 months (95% efficacy rate) Adverse effects G I upset, headache, Dizziness, rash Hepatic toxicity However, majority of women prefer single 150-mg oral dose of fluconazole which is safe and effective. 29 In pregnant and immuno-compromised patients prolonged course of treatment (1-2 weeks.) is recommended. 12

8 2.1.3: Trichomona vaginalis (TV): TV is the third most common cause of VVS (15-20% of VVS). 10 It is STD caused by an anaerobic, unicellular, flagellated protozoan. Women present with pruritus and increased vaginal discharge which is yellowish-green, frothy and malodorous. TV is the most common curable STD found among sexually active women. However, the management of trichomoniasis is often challenging. 32 Most infected males are asymptomatic, and up to 50% of females may be asymptomatic as well. 30 Like BV, the importance of TV extends beyond the vagina. During pregnancy, studies have demonstrated a link between TV infection and a higher risk for premature rupture of membranes, chorioamnionitis, and preterm birth. In the nonpregnant patient, TV infection is supposed to be a risk factor for the transmission of HIV, cervical neoplasia, atypical pelvic inflammatory disease, tubal infertility, and post-hysterectomy infection. 32 Diagnosis of Trichomona Vaginalis: The diagnosis of TV is typically made on the basis of vaginal pool wet mount examination. The presence of motile, pear-shaped organism, slightly larger than a WBC, TV which can be identifiable by its twisting, jerky motion in the smear is diagnostic of TV infection. Smear also shows an increase in number of WBCs (quantitatively as > 10 13

9 WBCs per high-power field and qualitatively by the number of WBCs exceeding the number of vaginal squamous cells). The sensitivity of the saline wet mount for TV is 49-78%. 10 An abnormal, alkaline vaginal ph (> 4.5) is suggestive of either BV or TV infection. Isolation of TV on vaginal culture is difficult. In recurrent infections and in cases where wet smear is negative, isolation can be achieved using modified Dimond s Oxide, Trichosel media. Treatment of Trichomona Vaginalis: The standard treatment for TV is a single 2 g oral dose of metronidazole. 27 It can be given in the dosage of 500 mg twice daily for seven days but it is usually reserved for those who fail to respond to single-dose therapy or unable to tolerate it. Common adverse reaction with metronidazole includes nausea, vomiting, dizziness and metallic taste. It is associated with di-sulfiram-like reaction. Hence patient need to be advised to avoid alcohol during and at least 24 hours after the last dose. 33 A second generation nitroimidazole-tinidazole can be used as an alternative to metronidazole, 2 gm single oral dose. It is the drug of choice for metronidazole resistant infections. It is better tolerated than metronidazole. Since T. vaginalis can colonize in the urethra and associated glands, topical therapy is less effective. Topical therapy is used only in the presence of intolerance to oral therapy. For recurrent infections same single dose therapy of metronidazole can be used or else a 7days course is also used. 14

10 Normal Discharge: A normal vaginal discharge is found in 10% of patients presenting with a 13, 32 vaginal discharge. A normal discharge is composed of vaginal squamous and columnar cells. A normal discharge is clear to slightly cloudy in appearance, nonhomogenous (eg, floccular, stringy, clumped, etc.), and viscous or sticky, not associated with itching, burning or emanate an offensive smell. An increased volume of discharge can be normally seen during pregnancy, following coitus or menstruation, and 35, 36, 37 prior to ovulation. Cervicitis: Among women presenting with vaginal complaints, cervicitis may be 13, 37 responsible for 5-20% of cases. Chlamydia trachomatis and Neisseria gonorrhoeae are the most common pathogens isolated and are commonly asymptomatic. 38 Other possible causes include TV, herpes simplex virus, Mycoplasma genitalium, cytomegalovirus, BV, and topical exposure to products that can disrupt or irritate the cervicovaginal mucosa (eg, spermicides, chemical douches and deodorants, etc.). 39 Cervicitis should be suspected in women found to have a yellow endocervical discharge, easily induced cervical bleeding, edema of the cervical ectropion, or leucorrhoea (> 10 white 15

11 blood cells [WBCs] per high-power field on microscopic examination of vaginal fluid) : Menstrual Disorders: 2.2.1: Dysmenorrhoea: Dysmenorrhoea refers to the occurrence of painful menstrual cramps of uterine origin and is a common gynaecological disorder affecting as many as 50% -70% of menstruating women. In 10-12% of women dysmenorrhoea interferes with daily activities. 40 The pain may be spasmodic type (starting few hours prior to onset of menstruation and lasting till first or second day of menstruation) or congestive type (pain starting few days prior to menstruation lasting till first 2-3 days of menstruation). Dysmenorrhoea is classified into two types: Primary dysmenorrhoea (PMD) Secondary dysmenorrhoea Primary refers to menstrual pain without pelvic pathology, whereas secondary is defined as painful menstruation associated with underlying pathology. Pathophysiology of Dysmenorrhoea: The etiology of the PMD is not precisely understood. However, most symptoms can be explained by the action of increased endometrial prostaglandin especially PGF 2α production. 41 Prostaglandins and leukotreins are found in higher concentration in 16

12 secretory endometrium than in proliferative endometrium. The decline of progesterone levels in the late leuteal phase triggers lytic enzymatic action, resulting in a release of phospholipids with generation of arachidonic acid and activation of cyclo-oxygenase (COX) pathway. Increased synthesis of prostanoids increases the tone of uterine myometrium resulting into high amplitude contractions causing dysmenorrhoea. It is theorized that women having dysmenorrhoea have upregulated COX enzyme activity. Management: Treatment of dysmenorrhea is aimed at providing symptomatic relief as well as inhibiting the underlying processes that cause symptoms. Medical management can be divided into three categories: Table No : Medical Management of Dysmenorrhoea I. Non-Hormonal Therapy 1. Nutritional 2. Non-steroidal anti-inflammatory drugs (NSAID) II. Hormonal Therapy 1. Steroid Hormone Contraceptives 2. Other Hormonal methods 3. Gonadotropin-Releasing Hormone Agonists and androgens 17

13 I. Non-Hormonal Therapy: 1. Nutritional : Several nutritional supplements have been indicated as effective in treating dysmenorrhoea. These include Vit. B 1 (thamine), Magnesium, Zinc, ginger, omega-3- fatty acids, Vit E. etc. 42 Research indicate that the underlying mechanism of dysmenorrhoea is imbalance between anti- inflammatory, vasodilator eicosanoids derived from Omega-3-fatty acids, and pro-inflammatory, vasoconstrictor eicosanoids derived from omega-6- fatty acids. Several studies indicated that intake of omega-3 fatty acids can reverse the symptoms of dysmenorrhoea, by decreasing the amount of omega-6- fatty acids Non-steroidal anti-inflammatory drugs (NSAID): Since prostaglandins are implicated in genesis of dysmenorrhoea, treatment with NSAID is logical and studies support their use. 44, 45 A Meta-analysis shows that COX-1 inhibitors such as mefenamic acid, naproxen, ibuprofen and aspirin are all effective. The drugs and their dosage are mentioned in Table no Patients in whom common NSAID are not effective or contraindicated, COX-2 inhibitors may be prescribed. 18

14 Table No : NSAIDs for the treatment of primary dysmenorrhea Sl. No. Drug Dosage Mode of action Side effects Ibuprofen Naproxen sodium mg every 6 h as needed mg initially, followed by mg every 8 h as needed Cox-1 inhibitors (thereby inhibiting prostaglandin production) Side effects nausea, vomiting, dyspepsia, peptic ulcer and 3. Mefenamic acid 500 mg initially, followed by 250 mg every 6 h as needed diarrhea. Renal failure on long term use 4. Celecoxib 400 mg initially, followed by 200 mg every 12 h as needed. Cox-2 inhibitor 19