Uterine cancer (cancer of the uterus)

Download: Bleeding – perimenopausal, postmenopausal and breakthrough bleeding on MHT/HRT | Information Sheet Key pointsA change in bleeding pattern is common during perimenopause.Heavy bleeding, prolonged bleeding, and any bleeding more than 12 months after the last menstrual period needs investigation.Endometrial ultrasound is the initial investigation of choice, and the findings determine the need for tissue sampling and/or hysteroscopy.Medical management, after excluding a localised or neoplastic lesion, involves modification of the MHT dose or regimen.Perimenopausal bleedingIn the menopausal transition, hormonal fluxes may be erratic with vaginal bleeding being both ovulatory or non-ovulatory, light, or heavy, reasonably regular, or entirely irregular (1). For women considering menopausal hormone therapy (MHT), abnormal bleeding should be investigated before prescribing. Heavy menstrual bleeding, rather than irregular bleeding itself is a hallmark of abnormal build-up of the endometrium. Heavy bleeding after a prolonged interval without bleeding, or prolonged bleeding of any amount should be investigated. A lower investigative threshold should apply for high-risk women.Postmenopausal bleedingPostmenopausal bleeding (PMB) refers to any vaginal bleeding that occurs in a menopausal woman, i.e. 12 months after their final menstrual period. This does not include the regular withdrawal bleed that occurs on MHT.Any postmenopausal bleeding requires investigation to exclude a sinister cause. The likelihood of endometrial carcinoma for a woman presenting with PMB is 10% (2). However, around 95% of women with endometrial malignancy will present with PMB (3). Risk factors for endometrial cancer include age, obesity, use of unopposed oestrogen, polycystic ovary syndrome (PCOS), Type 2 diabetes mellitus, atypical glandular cells on screening cervical cytology and family history of gynaecologic malignancy(4). Nulliparity is also a risk factor. Patients taking non-conventional MHT, such as troches and transdermal progestogen are at risk of endometrial hyperplasia and cancer (5).Women on menopausal hormone therapyIn women taking cyclical MHT, a withdrawal bleed is expected, and the patient should be counselled as such. The withdrawal bleed should occur toward the end of, or after the progestogen containing phase of the cyclical regimen. Bleeding, which is unpredictable, occurring outside the expected time, or excessively heavy should be investigated.For women taking continuous combined MHT (CCMHT), the significance of breakthrough bleeding depends upon the recency of her LMP and on how long she has been taking CCMHT. Women within 12 months of the last natural menstrual period often do not achieve amenorrhoea, presumably because some residual endogenously oestrogen-stimulated endometrium is present. Unpredictable breakthrough bleeding is common in this situation and does not need investigation unless it is unusually heavy. To avoid this, it is recommended that cyclical MHT be used for the first 12 months at least following the LMP. A similar diagnostic and therapeutic approach applies to tibolone.Bleeding should be investigated if it occurs after six months use of CCMHT or tibolone or starts after amenorrhoea has been established on this regimen. Amenorrhoea in this setting depends upon the balance between the oestrogenic effect and progestogenic effect of the MHT components on the endometrium. Oestrogen stimulation of the endometrium causes proliferative histological features and progesterone secretory. Inadequate progestogenic effect can therefore result in endometrial proliferation and possibly hyperplasia and bleeding. It may, like unopposed oestrogen therapy, lead to endometrial malignancy. However, more commonly in women taking pharmaceutical preparations of CCMHT, excessive progestogenic effect may produce bleeding from an atrophic endometrium.Diagnostic evaluation of postmenopausal bleeding (PMB)The primary goal of investigation is to exclude malignancy, and secondarily to elucidate a treatable non-malignant cause (6).A detailed history should be taken:When does the bleeding occur?Is it post-coital?What medications is the patient taking, e.g. anticoagulants, herbal therapies, tamoxifen?Is the patient taking so-called “bioidentical” hormones?Has the patient missed MHT doses?When was the last cervical screening test?Are there any bladder or bowel symptoms?Physical examination should include inspection of the vulva, vagina, and the cervix for visual evidence of lesions or bleeding, taking note of any signs of atrophy. Bleeding from the perineum, urethra and anus is also a possibility. A cervical co-test (HPV test and liquid based cytology) or cervical smear should be done.Endometrial ultrasoundEndometrial ultrasound is the initial investigation of choice. This should be done by an experienced specialist gynaecological ultrasonographer and with transvaginal ultrasound (TVUS). In women taking cyclical MHT, it should be done immediately after the withdrawal bleed (7). The ultrasound should be able to identify any localised uterine lesion which may contribute to bleeding – endometrial polyp, submucosal fibroid, hyperplasia, or cancer. The significance of PMB for the risk of malignancy differs with use of MHT and endometrial thickness on TVUS. Subsequent investigations depend on the ultrasound findings, so the experience of the ultrasonographer is critical. After excluding localised lesions, the following algorithm is useful (8). Note that this algorithm does not apply to women taking tamoxifen.Figure 1.  Management algorithm for patients with post-menopausal bleeding (8).  ECC= Endometrial echo complex, EC= Endometrial carcinoma, EMB= Endometrial biopsyTamoxifen therapyTamoxifen therapy is associated with stimulation of the endometrium and an increased risk of endometrial cancer (9). Tamoxifen therapy invariably produces a thickened appearance to the endometrium which is not always indicative of neoplasia. Therefore, TVUS is not useful for the investigation of PMB in a woman on tamoxifen therapy and examination of the uterine cavity by hysteroscopy is recommended (6).Histological assessmentThere has been some debate for what is regarded as the upper limit of normal endometrial thickness. Many groups have recently used a cut-off of 4mm (4,10,11). An endometrial thickness of ?4mm has a 99% negative predictive value for malignancy (4).Endometrial biopsy should be performed in women who meet the following criteria(4):Endometrial thickness >4mmNot easy display of the endometrium e.g. fibroidsPersistent PMBSuspicion of polyp or mass on transvaginal ultrasoundEndometrial thickness  ?  3mm with fluid in the endometrial cavityBlind tissue sampling such as Pipelle or D&C may be sufficient for pathology that affects the entire endometrial surface, but it is inadequate for detecting localised lesions such as endometrial polyps, which may be malignant (6). Hysteroscopy is superior to endometrial biopsy and ultrasonography for the identification of these structural lesions and is recommended.ManagementMedical managementWhen a localised or neoplastic lesion is found, the management is surgical. However, when the findings are benign and the patient is taking MHT, some modification of the MHT dose or regimen is required. While there is an abundance of literature about the incidence of bleeding on MHT and the histological findings, there are no evidence-based recommendations guiding therapeutic intervention. Therefore, the following recommendations are based on clinical practice advice from the literature and based on the patterns of histology seen in women with breakthrough bleeding (12-15). They are made here with the proviso that continued bleeding should prompt re-investigation, as above.Cyclical MHT with unpredictable bleeding and negative histological screen for pathologyThis may respond to a change in the progestogen component of the MHT such as altering the dose, type of progestogen or the mode of delivery e.g. intrauterine.CCMHT with breakthrough bleeding, endometrium >4mm and negative histologyIf less than 12 months post LMP, change to cyclical MHT or intrauterine progestogen. If more than 12 months post LMP, change oestrogen/progestogen balance by reducing oestrogen or changing progestogen dose, type, or delivery.CCMHT with breakthrough bleeding, endometrium <4mmThis is the most difficult scenario to manage, especially in a patient who wants to have no withdrawal bleeding. The TVUS suggests adequate, if not excessive, progestogenic effect, especially if tissue sampling demonstrates an atrophic sample. Increasing the dose or changing the progestogen formulation does not always address the underlying problem. Continuous progestogen effect on the endometrium exposes superficial dilated blood vessels which predispose to bleeding (16). The same may occur with prolonged tibolone therapy. A change back to cyclical MHT, at least for a while, is recommended or an increase in the oestrogen dose may be effective.Surgical managementSurgical management is appropriate for neoplastic and local lesions causing bleeding. However, women who have heavy or unmanageable breakthrough bleeding in the absence of pathology, may prefer to have a hysterectomy, after which they need take only oestrogen as MHT. The alternative is endometrial ablation. This may resolve the PMB but it should be noted that progestogen is still necessary since there will be residual endometrium left. Moreover, the above investigations – TVUS, hysteroscopy, endometrial sampling - will be difficult if there is subsequent PMB (17).ReferencesHale GE, Hughes CL, Burger HG, Robertson DM, Fraser IS. Atypical estradiol secretion and ovulation patterns caused by luteal out-of-phase (LOOP) events underlying irregular ovulatory menstrual cycles in the menopausal transition. Menopause. 2009;16(1):50-9.van Hanegem N, Breijer MC, Khan KS, Clark TJ, Burger MP, Mol BW, et al. Diagnostic evaluation of the endometrium in postmenopausal bleeding: an evidence-based approach. Maturitas. 2011;68(2):155-64.van Hanegem N, Prins MM, Bongers MY, Opmeer BC, Sahota DS, Mol BW, et al. The accuracy of endometrial sampling in women with postmenopausal bleeding: a systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2016;197:147-55.ACOG Committee Opinion No. 734: The Role of Transvaginal Ultrasonography in Evaluating the Endometrium of Women with Postmenopausal Bleeding. Obstet Gynecol. 2018;131(5):e124-e9.Eden JA, Hacker NF, Fortune M. Three cases of endometrial cancer associated with "bioidentical" hormone replacement therapy. Med J Aust. 2007;187(4):244-5.Munro MG, Southern California Permanente Medical Group's Abnormal Uterine Bleeding Working G. Investigation of women with postmenopausal uterine bleeding: clinical practice recommendations. Perm J. 2014;18(1):55-70.Affinito P, Palomba S, Sammartino A, Bonifacio M, Nappi C. Ultrasonographic endometrial monitoring during continuous-sequential hormonal replacement therapy regimen in postmenopausal women. Maturitas. 2001;39(3):239-44.Carugno J. Clinical management of vaginal bleeding in postmenopausal women. Climacteric. 2020;23(4):343-9.Mourits MJ, De Vries EG, Willemse PH, Ten Hoor KA, Hollema H, Van der Zee AG. Tamoxifen treatment and gynaecologic side effects: a review. Obstet Gynecol. 2001;97(5 Pt 2):855-66.Saccardi C, Spagnol G, Bonaldo G, Marchetti M, Tozzi R, Noventa M. New Light on Endometrial Thickness as a Risk Factor of Cancer: What Do Clinicians Need to Know? Cancer Manag Res. 2022;14:1331-40.Papakonstantinou E, Adonakis G. Management of pre-, peri-, and post-menopausal abnormal uterine bleeding: When to perform endometrial sampling? Int J Gynaecol Obstet. 2022;158(2):252-9.Stuenkel CA, Davis SR, Gompel A, Lumsden MA, Murad MH, Pinkerton JV, et al. Treatment of Symptoms of the Menopause: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2015;100(11):3975-4011.de Medeiros SF, Yamamoto MM, Barbosa JS. Abnormal bleeding during menopause hormone therapy: insights for clinical management. Clin Med Insights Women's Health. 2013;6:13-24.Spencer CP, Cooper AJ, Whitehead MI. Management of abnormal bleeding in women receiving hormone replacement therapy. BMJ. 1997;315(7099):37-42.Hillard TC, Siddle NC, Whitehead MI, Fraser DI, Pryse-Davies J. Continuous combined conjugated equine estrogen-progestogen therapy: effects of medroxyprogesterone acetate and norethindrone acetate on bleeding patterns and endometrial histologic diagnosis. Am J Obstet Gynecol. 1992;167(1):1-7.Thomas AM, Hickey M, Fraser IS. Disturbances of endometrial bleeding with hormone replacement therapy. Hum Reprod. 2000;15 Suppl 3:7-17.Harlow SD, Gass M, Hall JE, Lobo R, Maki P, Rebar RW, et al. Executive summary of the Stages of Reproductive Aging Workshop + 10: addressing the unfinished agenda of staging reproductive aging. Menopause. 2012;19(4):387-95.End of documentLast updated in September 2026

Download: Surgical Menopause | Information Sheet Key pointsRemoval of both ovaries (bilateral oophorectomy) before a woman has gone through her natural menopause is referred to as “surgical menopause”Bilateral oophorectomy may be performed at the time of hysterectomy for benign disease or gynaecological cancers, or as part of risk reduction treatment in women with an inherited increased cancer riskNegative effects of surgical menopause include a sudden onset of severe menopause symptoms, loss of fertility, and increased risks of osteoporosis, cardiovascular disease, sexual dysfunction, mood disorders and cognitive issuesMenopausal hormone therapy (MHT) is advised for all women who undergo surgical menopause before the age of natural menopause, provided they do not have contraindications to MHT use.What is surgical menopause?Menopause refers to the final menstrual period. The average age of menopause in Australia is around 51 years, but most women start to experience perimenopausal symptoms due to decreasing ovarian oestrogen levels from their mid-40s, starting with a change to their menstrual cycles (1). Surgical removal of both ovaries (bilateral oophorectomy) before the average age of natural menopause is referred to as surgical menopause. Earlier menopause may also occur due to other gynaecological procedures, such as uterine artery embolisation, hysterectomy with ovarian conservation, or ovarian cystectomy, presumably due to compromised ovarian blood supply (2,3).Indications for bilateral oophorectomyBilateral oophorectomy (usually with bilateral salpingectomy) is uncommonly performed at the time of hysterectomy for benign disease in premenopausal women, e.g. for management of heavy menstrual bleeding (4).A more common indication for this procedure is to reduce the risk of ovarian cancer; this is especially relevant and beneficial to women who carry an inherited increased risk of developing cancer due to gene mutations in BRCA or HNPCC (Lynch Syndrome), for example (5). In general, bilateral oophorectomy is not recommended for premenopausal women who are concerned about ovarian cancer risk but have no inherited increased risk, as the disadvantages of removing normal, healthy ovaries prior to the average age of menopause far outweigh the very small risk of ovarian cancer (6).Some premenopausal women may elect to have their ovaries removed for other indications, such as endometriosis, persistent pelvic pain, and premenstrual dysphoric disorder. Their healthcare provider may suggest a trial of medically-induced menopause prior to surgery for these women, both to test how surgical menopause may affect their underlying symptoms, and also to allow a trial of MHT to test for patient tolerance to the hormone therapy (7).Positive effects of surgical menopauseReduced risk of ovarian cancer in women who are at an increased risk due to inherited genetic mutationsReduced anxiety around developing ovarian cancer in this populationReduced symptoms of persistent pelvic pain, particularly in women with endometriosis or pelvic adhesions who have ovarian involvementReduced symptoms of premenstrual dysphoric disorderNegative effects of surgical menopauseSudden and severe onset of vasomotor symptoms (VMS) and genitourinary syndrome of the menopause (GSM)Loss of bone density and increased risk of osteoporosis and possibly fractures (8)Increased risk of cardiovascular disease and an associated increase in mortality risk (9,10)Increased risk of cognitive impairment, including dementia (11,12)Impaired sexual function due to GSM symptoms, and hypoactive sexual desire disorder (HSDD) due to loss of ovarian testosterone production (13)Increased long-term risk of depression and anxiety (14)Loss of fertility potentialManagement of surgical menopauseIdeally, a menopause specialist should review premenopausal women prior to them undergoing bilateral oophorectomy, to explain the potential adverse consequences of surgical menopause and to plan for symptom management and long-term health optimisation (2).Lifestyle management and ongoing monitoringEvidence-based lifestyle management strategies for reducing cardiovascular and cognitive risk, and for maintaining bone density, should be discussed. These may include advice around diet, exercise, smoking and alcohol, and ensuring adequate sleep and dietary calcium and vitamin D intake. Cardiovascular risk factors should be assessed annually. In Australia, women who are under the age of 45 who have been hypogonadal for 6 months or more are entitled to Medicare bone density scans, which should be performed every 2 years.Symptom managementCurrent international guidelines recommend the use of MHT for all women who undergo early menopause, even if they have minimal menopausal symptoms, provided that they do not have any contraindications to use (3, 15, 16). MHT should be commenced as soon as possible post-operatively, reviewed within 6-12 weeks for symptom response, and continued at least until the average age of menopause. MHT is highly effective at treating VMS and GSM in this population, although higher oestrogen doses may be required in younger women than that used at the average age of menopause, to achieve physiological doses of oestradiol (3, 15). MHT can be commenced at a standard dose and titrated up according to response and side-effects. MHT can be prescribed to women who have had a bilateral oophorectomy performed for cancer risk reduction, and who have no contraindications to its use, without increasing their risk of breast cancer (17). Most guidelines recommend changing these patients to non-hormonal treatments for VMS if they are still required beyond the age of natural menopause, although there is minimal evidence for this recommendation (16, 18).A progestogen needs to be used in women who retain their uterus and should be considered for women with a history of endometriosis, even if she has had a hysterectomy, due to concerns about disease and symptom recurrence (19). Tibolone may also be considered as MHT for women with a history of endometriosis (2). Given that higher oestrogen doses may be required for symptom management in younger women, correspondingly higher doses of a progestogen may also be necessary (3).Prevention of morbidity and mortalityWhile a lack of longitudinal outcome data currently exists for this population, MHT has been shown in observational studies to reduce risks of osteoporosis and fracture, cardiovascular morbidity and mortality, and cognitive issues (16). Observational data show a probable “window of opportunity” for MHT initiation early after surgical menopause, especially to mitigate cardiovascular and cognitive risk (3).Management of sexual dysfunction and psychosocial risksThe sexual and psychological dysfunction arising after surgical menopause is complex and is likely to arise not only due to hormonal changes but also due to potential early ageing, self-esteem and body-image issues, emerging mood disorders and concerns around loss of fertility (3). As such, a biopsychosocial model is often required for the management of both sexual and psychological concerns after surgical menopause.MHT may improve some aspects of sexual dysfunction and vaginal oestrogen or dehydroepiandrosterone can be added to systemic MHT to further improve GSM symptoms (15). In addition, for women with HSDD despite MHT use, testosterone therapy can be considered, but women need to be advised that long-term efficacy and safety are unknown (16, 20). Note that currently there is conflicting evidence for use of testosterone for other indications in patients with early menopause, specifically for neurological function, bone health and cardiovascular health (16).With regards to the increased long-term risk of a diagnosis of depression and/or anxiety following surgical menopause, given that these risks have only been identified in observational studies, it is unclear whether or not MHT use mitigates these risks (14).Further informationA Practitioner’s Toolkit for Managing MenopauseAMS guide to MHT/HRT doses – AustraliaAMS guide to MHT/HRT doses - New ZealandPremature ovarian insufficiency: International Menopause Society White Paper:Surgical menopause: a toolkit for healthcare professionals (British Menopause Society)ReferencesHarlow SD, Gass M, Hall JE, Lobo R, Maki P, Rebar RW, Sherman S, Sluss PM, de Villiers TJ; STRAW 10 Collaborative Group. Executive summary of the Stages of Reproductive Aging Workshop +10: addressing the unfinished agenda of staging reproductive aging. Menopause 2012; 19(4): 387-95.Hamoda H, Sharma A. Premature ovarian insufficiency, early menopause, and induced menopause. Best Practice & Research Clinical Endocrinology & Metabolism 2024; 38: 101823.Panay N, Anderson RA, Nappi RE, Vincent AJ, Vujovic S, Webber L, Wolfman W. Premature ovarian insufficiency: an International Menopause Society White Paper. Climacteric 2020; 23(5): 426-46.Hickey M, Ambekar M, Hammond I. Should the ovaries be removed or retained at the time of hysterectomy for benign disease? Human Reproduction Update 2009; 16(2):131-41.Rebbeck TR, Kauff ND, Domchek SM. Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers. Journal of the National Cancer Institute 2009; 101(2):80-87.Parker WH, Shoupe D, Border MS, Liu Z, Farquhar C, Berek JS. Elective oophorectomy in the gynaecological patient: when is it desirable? Current Opinion in Obstetrics and Gynecology 2007; 19(4):350-54.Green LJ, O'Brien PMS, Panay N, Craig M on behalf of the Royal College of Obstetricians and Gynaecologists. Management of premenstrual syndrome. British Journal of Obstetrics and Gynaecology 2017; 124: e73–e105.Gallagher JC. Effect of early menopause on bone mineral density and fractures. Menopause 2007; 14:567-71.Honigberg MC, Zekavat SM, Aragam K, Finneran P, Klarin D, Bhatt DL, Januzzi Jr JL, Scott NS, Natarajan P. Association of premature natural and surgical menopause with incident cardiovascular disease. Journal of the American Medical Association 2019; 322(24):2411-21.Rocca WA, Grossardt BR, de Andrade M, Malkasian GD, Melton LJ 3rd. Survival patterns after oophorectomy in premenopausal women: a population-based cohort study. Lancet Oncology 2006; 7(10):821-8.Bove R, Secor E, Chibnik LB, Barnes LL, Schneider JA, Bennett DA, De Jager PL. Age at surgical menopause influences cognitive decline and Alzheimer pathology in older women. Neurology 2014;82(3):222-9.Rocca WA, Bower JH, Maraganore DM, Ahlskog JE, Grossardt BR, de Andrade M, Melton LJ 3rd. Increased risk of cognitive impairment or dementia in women who underwent oophorectomy before menopause. Neurology 2007;69(11):1074-83.Nappi RE, Cucinella L, Martini E, Rossi M, Tiranini L, Martella S, Bosoni D, Cassani C. Sexuality in premature ovarian insufficiency. Climacteric 2019;22(3):289-295.Rocca WA, Grossardt BR, Geda YE, et al. Long-term risks of depressive and anxiety symptoms after early bilateral oophorectomy. Menopause 2018; 25:1275-85.Hamoda H in collaboration with the medical advisory council of the British Menopause Society. Premature ovarian insufficiency (Consensus Statement). Reviewed 2024. Premature ovarian insufficiency - British Menopause Society (thebms.org.uk)The ESHRE Guideline Group on POI, Panay N, Vincent AJ et al. ESHRE Guideline: management of women with premature ovarian insufficiency, 2024. https://www.eshre.eu/Guidelines-and-Legal/Guidelines/Premature-ovarian-insufficiencyGordhandas S, Norquist BM, Pennington KP, Yung RL, Laya MB, Swisher EM. Hormone replacement therapy after risk reducing salpingo-oophorectomy in patients with BRCA1 or BRCA2 mutations; a systematic review of risks and benefits. Gynecologic Oncology 2019;153:192-200.Gard A, Robinson L in collaboration with the medical advisory council of the British Menopause Society. Surgical menopause: a toolkit for healthcare professionals. Reviewed 2024. https://thebms.org.uk/wp-content/uploads/2021/06/13-BMS-TfC-Surgical-Menopause-JUNE202102B.pdfSecosan C, Balulescu L, Brasoveanu S, Balint O, Pirtea P, Dorin G, Pirtea L. Endometriosis in Menopause-Renewed Attention on a Controversial Disease. Diagnostics (Basel) 2020;10(3):134.Davis SR, Baber R, Panay N, Bitzer J, Cerdas Perez S, Islam RM, Kaunitz AM, Kingsberg SA, Lambrinoudaki I, Liu J, Parish SJ, Pinkerton J, Rymer J, Simon JA, Vignozzi L, Wierman ME. Global Consensus Position Statement on the Use of Testosterone Therapy for Women. Climacteric 2019;22(5):429-434.

In Australia, thyroid cancer is the ninth most commonly diagnosed cancer

In Australia, pancreatic cancer is the eighth most commonly diagnosed cancer

Breast cancer is the most common cancer in women and the second most common cause of cancer deaths in women in Australia.

In 2021, cervical cancer was estimated to be the 13th most commonly diagnosed cancer recorded among females, with 913 new cases of cervical cancer diagnosed in Australia.

Melanoma (melanocytic skin cancer) is the third most common invasive cancer diagnosed in Australia.

Prostate cancer is the most commonly diagnosed cancer in Australian men with an estimated 25,500 new cases in 2023, with around 1 in 7 eventually dying of prostate cancer.

Pancreatic cancer occurs when malignant cells develop in the pancreas, usually in the head of the pancreas. Unfortunately, pancreatic cancer has one of the lowest survival rates among all cancers, and is estimated to have the third-highest mortality rate after lung cancer and colorectal cancer.

In Australia, lung cancer is the fifth most commonly diagnosed cancer and is the leading cause of cancer death excluding non-melanoma cancers1