Clinical Guidelines for Women’s Health and Gynecological Care

Clinical Guidelines for Women’s Health and Gynecological Care

Ovarian Cancer

  • Symptoms and Detection: Historically, ovarian cancer was called the “silent killer”, but studies show symptoms do occur. Persistent symptoms representing a change from normal include bloating, pelvic or abdominal pain, difficulty eating or feeling full quickly, and urinary symptoms (urgency or frequency). These symptoms include fatigue, indigestion, back pain, pain with intercourse, constipation, and menstrual irregularities. Prompt medical evaluation can lead to earlier detection.
  • Physical Examination: Evaluation should include an abdominal, pelvic, and rectovaginal examination, as well as palpation of groin and supraclavicular lymph nodes. Findings suggestive of epithelial ovarian cancer include an adnexal mass, abdominal ascites, a mass in the mid to left upper abdomen (omental cake), pleural effusion, or groin/supraclavicular lymphadenopathy.
  • Investigations: If physical findings are abnormal or symptoms persist, evaluate patients with transvaginal and transabdominal ultrasound examination to assess the ovaries and check for ascites.
  • CA-125 Testing: CA 125 is the most commonly used laboratory test but has low sensitivity and low overall specificity (particularly in premenopausal women). We also suggest measuring serum CA 125 concentration. However, this tumor marker used alone does not perform well for diagnosis or exclusion of epithelial ovarian cancer in premenopausal patients. Moreover, one-half of patients with stage I epithelial ovarian cancer have a normal CA 125 level.

  • Conditions Associated with Elevated CA 125:

    • Gynecologic malignancies: Epithelial ovarian, fallopian tube, primary peritoneal, and endometrial cancers.
    • Benign gynecologic conditions: Benign neoplasms, functional cysts, endometriosis, Meigs syndrome, adenomyosis, leiomyomas, pelvic inflammatory disease, pregnancy, and menstruation.
    • Nongynecologic conditions/cancers: Cirrhosis, ascites, diverticulitis, pancreatitis, pleural effusion, pneumonia, heart failure, renal insufficiency, recent surgery, and various cancers (breast, colon, lung, liver, pancreas).
  • Screening: Routine screening for ovarian cancer in asymptomatic women is not recommended.

Contraception

UK Medical Eligibility Criteria (UKMEC) Summary (Key Contraindications):

  • Combined Hormonal Contraception (CHC): Unacceptable health risks (MEC 4) include smoking ≥15 cigarettes/day at age ≥35, breastfeeding up to <6 weeks postpartum, history of or current venous thromboembolism (VTE), migraine with aura at any age, current breast cancer, known thrombogenic mutations, systolic blood pressure ≥160 or diastolic ≥100, and vascular disease.
  • Breast Cancer: Current breast cancer is an unacceptable risk (MEC 4) for all hormonal methods (Cu-IUD, LNG-IUS, IMP, DMPA, POP, CHC).

Progesterone-Only Pill (POP) Options:

  • two types of POP available in Australia.
  • Levonorgestrel/norethisterone (Microlut/Noriday): Known as the mini-pill. If you are more than 3 hours late taking it, it is a missed pill.
  • Drospirenone (Slinda): Comes in a packet with 24 days of active hormone pills and four days of inactive sugar pills. This pill has a 24 hour missed pill window.

Intrauterine Devices (IUDs):

  • LNG-IUDs and copper IUDs are first-line contraceptives for females of all ages.
  • Mirena (52 mg levonorgestrel-releasing IUD) is replaced every 8 years and has indications for contraception, the management of heavy menstrual bleeding, and the prevention of endometrial hyperplasia (for up to 5 years) in individuals using estrogen for menopausal hormone therapy.

Etonogestrel Implant (Implanon NXT):

  • Advantages: highly effective, lasts for 3 years, safe postpartum. Disadvantages: altered bleeding patterns, requires a procedure, risk of deep insertion.
  • Starting: It is Immediately effective if inserted on day 1 to 5 of a regular menstrual cycle, less than 21 days postpartum, or within 5 days of an abortion. Otherwise, it takes 7 days to become effective.
  • Quick Start Method: When pregnancy cannot be definitively excluded, advise condom use or abstinence for seven days and organise a urine pregnancy test in four weeks.
  • Troublesome Bleeding: Exclude infection, interacting medications and gynaecological pathology. If no contraindications, offer the combined hormonal contraceptive pill (continuously or cyclically for a three-month trial). Other options include a five-day course of an NSAID or tranexamic acid 500 mg bd, or advising patients to self-manage bleeding episodes.

Depot Medroxyprogesterone Acetate (DMPA):

  • Injected deep intramuscularly (preferred site is the gluteal muscle) every 12 weeks.
  • Efficacy: Immediately effective if started on day 1 to 5 of a cycle. Otherwise, it takes 7 days to become effective. If there was unprotected sex since injection over more than 14 weeks or 3 weeks ago, perform a Quick Start and give levonorgestrel emergency contraception. Test for pregnancy 3 weeks after the last episode of unprotected sex.
  • Risks: Assess risk factors for low bone mineral density and cardiovascular disease annually. It is recommended that females aged 50 years or older switch to another method of contraception, because the harms of depot medroxyprogesterone outweigh the benefits at this age.
  • Side effects: Irregular, prolonged or frequent bleeding is common. Around 50 to 70% of users will be amenorrhoeic after 1 year. Manage bleeding (after excluding pregnancy and chlamydia) with a combined hormonal contraceptive (up to 3 months), a 5-day course of a nonsteroidal anti-inflammatory drug (NSAID), tranexamic acid, adding a levonorgestrel progestogen-only pill, or adding oral norethisterone. Consider other causes for headaches, mood changes, breast tenderness, loss of libido.

Stopping Contraception at Menopause:

  • Women aged ≥50 years using non-hormonal methods should wait for 12 months of amenorrhoea, whereas those aged <50 years are advised to wait for 24 months.
  • Diagnosis of menopause is complicated in those aged below 50 years or For patients using an LNG IUD, contraceptive implant or progestogen-only pills who have been amenorrhoeic for at least 12 months since turning 50. Here, a single-serum follicle stimulating hormone (FSH) level can be used to determine the need for ongoing contraception.

Abnormal Vaginal Bleeding

Post-menopausal Bleeding:

  • All cases require investigation with a co-test (HPV & LBC) and a referral for gynaecological assessment.
  • Causes include atrophic endometritis and vaginitis (60-80%), exogenous oestrogens (15-25%), endometrial polyps (2-12%), endometrial hyperplasia (5-10%), and endometrial carcinoma (10%). postmenopausal bleeding primary goal is to exclude malignancy.
  • For patients with recurrent or persistent bleeding, further diagnostic evaluation (eg, dilation and curettage with hysteroscopy, saline infusion sonography) is indicated.

Heavy Menstrual Bleeding (HMB):

  • Definition: Excessive menstrual bleeding that interferes with physical, emotional, social, and material quality of life. Functional causes include haemostasis, coagulopathy, ovulatory dysfunction, or being iatrogenic (e.g., intrauterine contraceptive, anticoagulant, tamoxifen, estrogens, ginseng, ginkgo, soya). Coagulopathy, such as von Willebrand disease, can cause heavy periods from menarche. Ovulatory dysfunction is often due to polycystic ovary syndrome or hypothyroidism. Fibroids are the most common uterine pathology alongside adenomyosis and hyperplasia.
  • Investigation: Perform cervical screening and check full blood examination and serum ferritin concentration to assess for iron-deficiency anaemia. Consider coagulation screening in adolescents and checking a thyroid profile. Arrange an ultrasound on days 5 to 10 to measure endometrial thickness if there are indications for referral (e.g., fibroids, endometriosis or adenomyosis) or if bleeding has not responded to 6 months of medical therapy.
  • Specialist Referral: Needed if bleeding has not settled after 6 months; if there is concurrent severe dysmenorrhoea that does not settle after 3 months; if the patient wants to conceive; if ultrasound reveals fibroids greater than 3 cm or endometrial polyps; or if there is an increased risk of endometrial cancer (risk factors include oligomenorrhoea, polycystic ovary syndrome, tamoxifen use, obesity, age older than 45 years, or increased endometrial thickness measured in the first half of the menstrual cycle).

Hormonal Therapy for HMB:

  • LNG-IUD: The most effective medical therapy. Some irregular bleeding may be expected during the first few months after the 52 mg LNG-IUD has been inserted. It offers endometrial protection as part of HRT (5 years) and acts as a treatment using Mirena for heavy menstrual bleeding.
  • Combined hormonal contraception: Extended or continuous use minimises withdrawal bleeding.
  • Oral progestogens: Less effective than the LNG-IUD or tranexamic acid and nonsteroidal anti-inflammatory drugs (COCs). Have side effects like breast tenderness, irregular bleeding and headaches. Although the likelihood of conception is reduced during cyclical oral progestogen use, contraceptive efficacy has not been studied. Regimens: For Regular cycles, medication must be given for at least 21 days (e.g., medroxyprogesterone daily on days 1 to 21 of a 28-day cycle or norethisterone 5 mg orally daily on days 5 to 26 of a 28-day cycle). For Irregular cycles, use on the same 12 days of each calendar month. The progestogen-only contraceptive pill is not recommended for heavy menstrual bleeding.
  • depot medroxyprogesterone can be used and induces amenorrhoea after a year in 50 to 70% of individuals.

Nonhormonal Therapy for HMB:

  • Tranexamic acid: It reduces blood loss more than nonsteroidal anti-inflammatory drugs (NSAIDs) or oral progestogens.
  • NSAIDs (Ibuprofen, Mefenamic Acid): Start just before or at onset of menstrual bleeding and continue for up to 5 days.
  • Acute Severe Heavy Uterine Bleeding: Investigate for coagulation disorders (especially in adolescents) or anovulatory cycles. Hormonal treatment includes medroxyprogesterone 10 mg orally, every 4 to 8 hours until bleeding stops OR norethisterone 5 to 10 mg orally, every 4 to 8 hours until bleeding stops.

Polycystic Ovary Syndrome (PCOS)

  • Evaluation of Secondary Amenorrhea: Patient with secondary amenorrhea: Absence of menses for more than three months in girls or women who previously had regular menstrual cycles. Absence of menses for more than six months in girls or women who had irregular menses. Consider checking FSH, PRL, TSH, and for Pregnant status. History should assess: History: Weight change, eating disorder, excessive exercise, galactorrhea, hot flashes, acne, hirsutism, systemic illness, history of uterine instrumentation? Exam: Low BMI or obesity, signs of hyperandrogenism, galactorrhea.
  • Elevated prolactin suggests Hyperprolactinemia. Check for Further evaluation and treatment of thyroid disease.

  • In the setting of amenorrhea, a high FSH is typically seen with a low E2. Hot flashes and vaginal dryness are common symptoms. Diagnosis: Primary ovarian insufficiency.

  • Hypogonadotropic hypogonadism: Functional hypothalamic amenorrhea. Systemic illness (celiac disease or type 1 diabetes mellitus). Other hypothalamic or pituitary disorders.

  • If evidence of hyperandrogenism, PCOS is most likely diagnosis. If serum T >150 ng/dL or there is evidence of virilization, additional evaluation is needed to rule out more serious causes of hyperandrogenemia.
  • Diagnosis: Requires an adult to meet two of the following: menstrual disturbance, clinical or biochemical hyperandrogenism, or polycystic appearance of ovaries on ultrasound. Also common are obesity, insulin resistance, and subfertility. PCOS requires exclusion of differential diagnoses.
  • Diagnostic Steps: If ONLY irregular cycles OR hyperandrogenism are present, exclusion tests include TSH, prolactin, 17-OH progesterone, FSH. Adolescents: Ultrasound or AMH is not indicated – consider at risk of PCOS and reassess later.
  • Biochemical Hyperandrogenism: The main tests are total testosterone and free testosterone. If not elevated, then androstenedione and dehydroepiandrosterone sulfate could be measured. Reliable assessment of biochemical hyperandrogenism not possible on hormonal contraception. Consider withdrawal for >= 3 months with alternative contraception. A Biochemical hyperandrogenism role is when clinical hyperandrogenism is unclear.
  • Ultrasound: With irregular menstrual cycles and hyperandrogenism, an ovarian ultrasound is not necessary for diagnosis. Furthermore, Ultrasound should not be used for PCOS diagnosis in adolescents, due to the high incidence of multi-follicular ovaries in this life stage. Instead, Serum AMH could be used for defining PCOM in adults as an alternative to pelvic ultrasound. Either serum AMH OR ultrasound may be used but not both to avoid overdiagnosis.
  • Treatment Objectives: Address consequences of anovulatory cycles (irregular menstrual bleeding, subfertility), excess androgens (hirsutism, acne, androgenetic alopecia), obesity, insulin resistance (and hyperandrogenism / cardiovascular risk), and poor mental health). Treatment focuses on individual components of the syndrome (e.g., Weight loss, Oral contraceptives, menstrual dysfunction, contraception, androgenicity, norethindrone, spironolactone, pregnancy). Refer for specialist assessment if diagnosis is uncertain, hirsutism is non-responsive, or the patient is seeking fertility treatment.

Management Strategies:

  • Weight control in PCOS: Losing 5% of total body weight improves metabolic, reproductive and mental health in individuals with PCOS. It treats menstrual disturbance, infertility, obstructive sleep apnoea, insulin resistance and type 2 diabetes, cardiovascular disease, poor mental health, and nonalcoholic fatty liver disease. Consider metformin as an adjunct to lifestyle measures in weight management for individuals with PCOS.
  • Combined oral contraceptives (COCs) provide the most effective menstrual regulation in PCOS; they have the added benefit of suppressing ovarian androgen production, which can be beneficial for hirsutism, acne and androgenetic alopecia. Combined oral contraceptives provide the most effective menstrual regulation in PCOS. Use extended or continuous use to avoid withdrawal bleeding. If COCs are contraindicated, the 52 mg levonorgestrel-releasing intrauterine contraceptive device (LNG-IUD) can be used.
  • Metformin: it can be considered for individuals with a high risk of developing type 2 diabetes, subfertility, or a body mass index (BMI) greater than 25. It improves the frequency of ovulation in individuals with PCOS and it can be used in managing subfertility. Dose is up to a maximum of 1500 mg daily in 2 or 3 divided doses.

Menopausal Hormone Therapy (MHT)

  • Indications: Treating vasomotor, sleep, and mood symptoms, preventing osteoporosis, and preventing cardiovascular disease in individuals with premature ovarian insufficiency or early menopause.
  • Contraindications: Systemic MHT must not be started without specialist referral if there are contraindications including: age 60 years or older, previous venous thromboembolism, previous transient ischaemic attack/stroke/MI, uncontrolled hypertension, estrogen-dependent cancer, undiagnosed vaginal bleeding, high risk of breast cancer, significant liver disease, or SLE. Note: Starting systemic MHT is contraindicated in individuals aged 60 years or older, but continuing systemic MHT in this age group is not contraindicated. Also, Individuals with an increased risk of VTE can use transdermal but not oral MHT. Systemic MHT in individuals with a past history of VTE requires specialist advice. Lastly, Individuals with a familial risk of breast cancer may be able to use systemic menopausal hormone therapy but need individual risk assessment; refer those at high familial risk for specialist assessment.

Types of Systemic MHT:

  • estrogen-only: Used continuously in individuals who have had a total hysterectomy.
  • cyclical combined: Estrogen continuously with progestogen for 10-14 days. Used in individuals who are perimenopausal or have premature ovarian insufficiency.
  • continuous combined: Used in individuals who are postmenopausal, individuals where withdrawal bleeding is becoming lighter, or those with premature ovarian insufficiency or migraines.
  • other (tibolone): A synthetic steroid used in postmenopausal individuals as an alternative to continuous combined MHT. It has estrogenic, progestogenic and androgenic actions. Tibolone may improve libido. It increases the risk of breast cancer recurrence. However, Tibolone is not associated with an increased risk of venous thromboembolism.

Benefits and Harms:

  • combined MHT reduces the risk of fractures, diabetes, and colorectal cancer (combined only), as well as vasomotor symptoms. It increases the risk of invasive breast cancer (combined only), stroke, venous thromboembolism, gallbladder disease, dementia, urinary incontinence, and coronary heart disease.
  • estrogen-only MHT reduces the risk of fractures, diabetes, and vasomotor symptoms. It increases the risk of stroke, venous thromboembolism, gallbladder disease, and urinary incontinence.

Systemic MHT in Migraine:

  • Hormonally sensitive migraines may worsen with fluctuating estrogen. Some migraine types may be associated with an increased risk of stroke. For migraine sufferers, transdermal formulations are preferred. If a progestogen is needed, continuous combined MHT is compared to cyclical combined MHT. If auras or headaches become more intense or prolonged when taking MHT, stop therapy. Clonidine is a useful nonhormonal alternative for hot flushes.

Intravaginal Estrogen Therapy:

  • It is not associated with increased risk of cardiovascular disease, venous thromboembolism, or breast cancer, making it generally safe (though nonhormonal options are preferred if there is a personal history of breast cancer). It treats vulvovaginal atrophy, urinary symptoms, and recurrent infections, but has a limited role in treating incontinence.

Nonhormonal Medications for Menopause:

  • Used for managing vasomotor symptoms.
  • Gabapentinoids (gabapentin/pregabalin): Use if hot flushes are worse at night or accompanied by poor sleep.
  • Clonidine: Use for individuals with hot flushes who also require migraine prevention. An adverse effect is the reduction of blood pressure.
  • SSRIs and SNRIs: Used for hot flushes and mood symptoms. Escitalopram is the most effective SSRI for improving vasomotor symptoms, quality of life, and sleep. Do not use fluoxetine and paroxetine in individuals taking tamoxifen; consider an SNRI or an alternative SSRI. (Because they inhibit CYP450, altering tamoxifen metabolism).