Management of menopausal symptoms after cancer and risk-reduction bilateral oophorectomy: a move towards consensus

Abstract Background: Autoimmune progesterone dermatitis (APD) is a rare skin condition caused by sensitivity to high levels of progesterone secreted during the luteal phase of the menstrual cycle. This may be due to various pathophysiological mechanisms including a Type I and Type IV hypersensitivity reaction, and potential cross-reactivity with other endogenous steroid hormones such as 17-α-hydroxyprogesterone. We present the case of a patient with APD who had her flare-up episodes controlled using omalizumab, after a bilateral oophorectomy failed to resolve her symptoms. Clinical Case: A 34-year-old female presented to our Endocrine Clinic with marked Cushingoid features secondary to high-dose oral prednisone prescribed for APD diagnosed six years earlier. She first developed a pruritic maculopapular rash on her arms and legs just after the birth of her second child in 2009. The rash was also associated with headaches and diffuse angioedema. It presented in a cyclical fashion, beginning one to two days before the start of her menstrual cycle, and ending shortly after it was complete. The severity of symptoms increased as time went on, and flare-ups began to also include dyspnea, nausea, vomiting and abdominal pain. After three years of persistent symptoms, the diagnosis of APD was confirmed by a progesterone skin test. Her symptoms were improved with oral prednisone use, however breakthrough episodes still occurred. After multiple failed treatment modalities, she elected bilateral oophorectomy in 2018. However, her symptoms of APD persisted and she still required high-dose oral prednisone. Her condition was further complicated by vasomotor menopausal symptoms and progressive iatrogenic Cushing’s syndrome. She eventually was started on Omalizumab, which helped resolve her APD symptoms and allowed her to wean off prednisone. Vasomotor menopausal symptoms were resolved using conjugated estrogens with bazedoxifene. However, her symptoms of diffuse bony indeterminate bony pain and arthralgias which started whilst on prednisone have persisted in spite of discontinuing prednisone. Conclusion: To our knowledge, this is only the third case of APD which was successfully treated with Omalizumab and the first case where a bilateral oophorectomy failed to resolve symptoms of APD in the literature. Our case also demonstrates the complications of vasomotor menopause symptoms secondary to a bilateral oophorectomy, as well as the adverse effects of long-term glucocorticoid therapy.

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Menopausal hormone therapy: Characterising users in an Australian national cross-sectional study

PLoS ONE ◽

10.1371/journal.pone.0253725 ◽

2021 ◽

Vol 16 (8) ◽

pp. e0253725

Author(s):

Louiza S. Velentzis ◽

Sam Egger ◽

Emily Banks ◽

Karen Canfell

Keyword(s):

Logistic Regression ◽

Hormone Therapy ◽

Multinomial Logistic Regression ◽

Personal Characteristics ◽

Cross Sectional Study ◽

Menopausal Symptoms ◽

Menopausal Hormone Therapy ◽

Bilateral Oophorectomy ◽

Cross Sectional Survey ◽

Cross Sectional

Menopausal hormone therapy (MHT) is effective for menopausal symptoms, however, its use is also associated with risks of serious health conditions including breast, ovarian and endometrial cancer, stroke and venous thromboembolism. MHT-related health risks increase with longer durations of use. In Australia, while overall MHT use fell when risk-related findings were published in 2002, a significant number of women continue using MHT long-term. We aimed to examine socio-demographic, health-related and lifestyle characteristics in relation to post-2002 MHT use, and to compare use for <5 and ≥5 years. Data from 1,561 participants from an Australian, national, cross-sectional survey of women aged 50–69 in 2013 were analysed. Odds ratios (ORs) were calculated using logistic regression for characteristics related to overall MHT use post-2002 and multinomial logistic regression for associations between MHT duration of use [never/<5 years/≥5 years] and personal characteristics, adjusting for sociodemographic, reproductive, health and lifestyle factors. Post-2002 MHT use was associated with increasing age (p-trend<0.001), hysterectomy versus no hysterectomy (OR:2.55, 95%CI = 1.85–3.51), bilateral oophorectomy vs no oophorectomy (OR:1.66, 95%CI = 1.09–2.53), and ever- versus never-use of therapies other than MHT for menopausal symptoms (OR:1.93, 95%CI = 1.48–2.57). Women with prior breast cancer (OR:0.35, 95%CI = 0.17–0.74) and with more children (p-trend = 0.034) were less likely than other women to use MHT. Prior hysterectomy was more strongly associated with MHT use for ≥5 years than for <5 years (p = 0.004). Ever-use of non-MHT menopausal therapies was associated with MHT use for <5 years but not with longer-term use (p = 0.004). This study reinforces the need for MHT users and their clinicians to re-evaluate continued MHT use on an ongoing basis.

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Does a Multidisciplinary Menopausal Symptoms after Cancer Clinic Reduce Symptoms?

10.21203/rs.3.rs-552369/v1 ◽

2021 ◽

Author(s):

Jade Hollingworth ◽

Lucy Walsh ◽

Stephanie Tran ◽

Lesley Ramage ◽

Shavita Patel-Brown ◽

...

Keyword(s):

Management Strategies ◽

Significant Proportion ◽

Patient Reported Outcome ◽

Clinic Visit ◽

Menopausal Symptoms ◽

Care Clinic ◽

Patient Reported ◽

After Cancer ◽

Multidisciplinary Model

Abstract PurposeThis study aimed to measure the prevalence of menopausal symptoms in patients attending a multidisciplinary model of care clinic at their initial clinic visit and their subsequent follow-up consultation using a validated patient reported outcome measure to assess whether menopausal symptoms after cancer had improved.MethodsA retrospective review was conducted of patients attending the clinic in a 12-month period in 2017 (n=189). Recorded variables included patient demographics, details of index cancer, previous treatments and menopausal symptom management strategies. Severity of menopausal symptoms was evaluated using the Greene Climacteric Scale. The extent to which patients were bothered by symptoms were combined into two categories and dichotomized (present/absent). Differences in symptom prevalence between the initial consultation and first follow-up visit were examined using McNemar’s Test. ResultsThe majority of patients attending the clinic had a history of breast cancer (72%). 55% of patients were prescribed a non-hormonal therapy at their initial visit, most commonly gabapentin. Significantly fewer patients reported being bothered by hot flushes, fatigue, sleep difficulties and loss of interest in sex, anxiety or troubles concentrating at the first follow-up visit compared to their initial consultation (p < 0.01). ConclusionIn this study there was an improvement in self-reported menopausal symptoms in a significant proportion of cancer survivors attending a multidisciplinary menopause clinic between their initial and first subsequent follow-up consultations.

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Management of menopausal symptoms and ovarian function preservation in women with gynecological cancer

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2020-002032 ◽

2020 ◽

pp. ijgc-2020-002032

Author(s):

Annabelle Brennan ◽

Donal Brennan ◽

Margaret Rees ◽

Martha Hickey

Keyword(s):

Hormone Therapy ◽

Hormone Receptors ◽

Ovarian Function ◽

Gynecological Cancer ◽

Hormone Replacement ◽

Estrogen Therapy ◽

Menopausal Symptoms ◽

Health Concern ◽

Gynecological Cancers ◽

Bilateral Oophorectomy

Gynecological cancers affect a growing number of women globally, with approximately 1.3 million women diagnosed in 2018. Menopausal symptoms are a significant health concern after treatment for gynecological cancers and may result from oncologic treatments such as premenopausal bilateral oophorectomy, ovarian failure associated with chemotherapy or radiotherapy, and anti-estrogenic effects of maintenance endocrine therapy. Additionally, with the growing availability of testing for pathogenic gene variants such as BRCA1/2 and Lynch syndrome, there is an increasing number of women undergoing risk-reducing oophorectomy, which in most cases will be before age 45 years and will induce surgical menopause. Not all menopausal symptoms require treatment, but patients with cancer may experience more severe symptoms compared with women undergoing natural menopause. Moreover, there is increasing evidence of the long-term implications of early menopause, including bone loss, cognitive decline and increased cardiovascular risk. Systemic hormone therapy is well established as the most effective treatment for vasomotor symptoms and vaginal (topical) estrogen therapy is effective for genitourinary symptoms. However, the role of hormone receptors in many gynecological cancers and their treatment pose a challenge to the management of menopausal symptoms after cancer. Consequently, the use of menopausal hormone therapy in this setting can be difficult for clinicians to navigate and this article aims to provide current, comprehensive guidance for the use of menopausal hormone replacement therapy in women who have had, or are at risk of developing, gynecological cancer to assist with these treatment decisions.

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Effect of Omalizumab for Autoimmune Progesterone Dermatitis Refractory to Bilateral Oophorectomy: a case report

10.21203/rs.3.rs-108412/v1 ◽

2020 ◽

Author(s):

Akshay Varghese ◽

Terri Paul ◽

Harold Kim ◽

Stan Van Uum ◽

Peter Vadas ◽

...

Keyword(s):

Menstrual Cycle ◽

Oral Prednisone ◽

Maculopapular Rash ◽

Menopausal Symptoms ◽

Treatment Modalities ◽

High Dose ◽

Type I ◽

Bilateral Oophorectomy ◽

First Case ◽

Dose Oral

Abstract Background Autoimmune progesterone dermatitis (APD) is a rare skin condition caused by sensitivity to high levels of progesterone secreted during the luteal phase of the menstrual cycle. This may be due to various pathophysiological mechanisms including a Type I and Type IV hypersensitivity reaction. Here we present the case of a patient with APD whose episodic flares were controlled by the addition of omalizumab, after a bilateral oophorectomy failed to resolve her symptoms. Case Presentation A 34-year-old female presented to our Endocrine Clinic with marked Cushingoid features secondary to high-dose oral prednisone prescribed for APD diagnosed 6 years earlier. She first developed a pruritic maculopapular rash on her arms and legs just after the birth of her second child in 2009. The rash was also associated with headaches and diffuse angioedema. It presented in a cyclical fashion, beginning one to two weeks before the start of her menstrual cycle, and ending shortly after it was complete. The severity of symptoms increased as time went on, and flare-ups began to also include dyspnea, nausea, vomiting and abdominal pain. Her symptoms improved with administration of oral prednisone, but she continued to experience breakthrough symptoms. After multiple failed treatment modalities, she elected bilateral oophorectomy in 2018. However, her symptoms of APD persisted and she still required high-dose oral prednisone. Her condition was further complicated by vasomotor menopausal symptoms and progressive iatrogenic Cushing’s syndrome. She eventually was started on Omalizumab, which suppressed further recurrences of APD symptoms and allowed her to wean off prednisone. Vasomotor menopausal symptoms responded well to the addition of conjugated estrogens with bazedoxifene. However, her symptoms of diffuse bony pain and arthralgias which started whilst on prednisone have persisted in spite of discontinuing prednisone. Conclusions To our knowledge, this is only the third case of APD which was successfully treated with Omalizumab and the first case where a bilateral oophorectomy failed to resolve symptoms of APD in the literature. This case also demonstrates the complications of vasomotor menopausal symptoms secondary to a bilateral oophorectomy, as well as the adverse effects of long-term glucocorticoid therapy.

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Analysis of clusters of menopausal disorders associated with a decrease in the quality of life in postovarectomy and climacteric syndromes

"Medical & pharmaceutical journal "Pulse" ◽

10.26787/nydha-2686-6838-2021-23-5-64-71 ◽

2021 ◽

pp. 64-71

Author(s):

Neufeld I.V. ◽

Bobyleva I.V. ◽

Zhirnyakov A.I. ◽

Kuznetsova M.V. ◽

Rogozhina I.E.

Keyword(s):

Quality Of Life ◽

Sleep Disturbances ◽

Estrogen Deficiency ◽

Menopausal Symptoms ◽

Moderate Degree ◽

Bilateral Oophorectomy ◽

Menopausal Syndrome ◽

Natural Menopause ◽

Surgical Menopause

The decline in the quality of life due to various menopausal disorders in the early postmenopausal period is actually the main reason that leads a woman to seek medical help. Despite this, not enough attention is paid to this problem. Currently, the concept of the formation of individual menopausal symptoms into clusters is emerging to optimize treatment and diagnostic algorithms for managing this category of patients. The aim was a comparative analysis of the menopausal disorders most associated with a decrease in the quality of life. Included were 230 women with climacteric disorders (95 with bilateral oophorectomy; 135 with natural menopause). The assessment of the severity of climacteric disorders was carried out according to the Kuperman index modified by E.V. Uvarova. The SF-36 Health Status Survey was used to assess the quality of life. The average age of patients with surgical menopause was 47.9±2.2 years, with natural menopause - 53.6±3.5 years (p˂0.05). The duration of the estrogen deficiency state in the groups was comparable - 2.8 ± 0.6 years (p>0.05). All patients had a moderate degree of menopausal syndrome (p>0.05), however, the values of the modified menopausal index differed significantly: with postovarectomy syndrome - 57.8±1.1 points, with menopausal syndrome - 49.7±0.9 points (р <0.05). In both groups, a decrease in the quality of life was observed: the total physical component (with postovarectomy syndrome up to 57.2 (36.6; 72.7), with menopause - up to 68.4 (49.3; 83.5)) and the total psychological component (up to 53.9 (42.9; 76.7) and 64.1 (47.3; 84.5), respectively). In contrast to our approach, the formation of clusters of menopausal symptoms, based on the generally accepted approach to the analysis of climacteric disorders (psychological, vasomotor, somatic), provided a significantly smaller sample coverage (with surgical menopause - 68.5%, with natural - 62.6% variance) With a duration of estrogen deficiency of 2.8 ± 0.6 years, the cluster of menopausal disorders, which has the maximum negative effect on the quality of life, includes symptoms: hot flashes, cognitive disorders, sleep disturbances, anxiety, and covers 80.3% of the variance in postovarectomy syndrome, in menopausal - 73.6%. Knowledge of this fact contributes to the identification of risk groups and allows formulating new algorithms for the management of postmenopausal women.

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Managing menopausal symptoms after cancer

Climacteric ◽

10.1080/13697137.2019.1646718 ◽

2019 ◽

Vol 22 (6) ◽

pp. 572-578 ◽

Cited By ~ 5

Author(s):

R. A. Szabo ◽

J. L. Marino ◽

M. Hickey

Keyword(s):

Menopausal Symptoms ◽

After Cancer

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2122

Journal of Clinical and Translational Science ◽

10.1017/cts.2017.96 ◽

2017 ◽

Vol 1 (S1) ◽

pp. 24-24

Author(s):

Lisa M. Shandley ◽

Lauren M. Daniels ◽

Jessica B. Spencer ◽

Ann C. Mertens ◽

Penelope P. Howards

Keyword(s):

Breast Cancer ◽

Cancer Survivors ◽

Unintended Pregnancy ◽

Cancer Diagnosis ◽

Breast Cancer Survivors ◽

The United States ◽

Population Based ◽

Reproductive Age ◽

Bilateral Oophorectomy ◽

After Cancer

OBJECTIVES/SPECIFIC AIMS: In the United States, it is estimated that approximately half of all pregnancies are unintended. This study examines the prevalence of unintended pregnancy in a cohort of cancer survivors and identifies factors associated with unintended pregnancy after cancer. METHODS/STUDY POPULATION: The FUCHSIA Women’s Study is a population-based study of female cancer survivors at a reproductive age of 22–45 years. Cancer survivors diagnosed between the ages of 20 and 35 years and at least 2 years postdiagnosis were recruited in collaboration with the Georgia Cancer Registry. Participants were interviewed about their reproductive histories. The prediagnosis analysis included all women who completed the interview; the postdiagnosis analysis excluded those who had a hysterectomy, bilateral oophorectomy, or tubal ligation by cancer diagnosis. RESULTS/ANTICIPATED RESULTS: Of the 1282 survivors interviewed, 57.5% reported at least 1 pregnancy before cancer diagnosis; of which, 44.5% were unintended. Of the 1088 survivors included in the postdiagnosis analysis, 36.9% reported a post-cancer pregnancy. Among those who had a pregnancy after cancer diagnosis, 38.6% reported at least 1 pregnancy was unintended. Of the 80 breast cancer survivors who had a pregnancy after diagnosis, 52.5% of them were unintended. Predictors of unintended pregnancy in cancer survivors included being younger than 30 years at diagnosis [odds ratio (OR) 2.1; 95% confidence interval (CI) 1.4, 2.9], identifying as Black (OR 1.6, 95% CI 1.1, 2.3, comparison: White), and having resumption of menses after cancer treatment (OR 8.1, 95% CI 2.0, 33.0). Compared with being <4 years from cancer diagnosis, those who were farther from diagnosis at the time of the interview also had increased odds of unintended pregnancy (4–7 years: OR 1.5, 95% CI 0.9, 2.7; 8–10 years: OR 1.3, 95% CI 0.7, 2.4; >10 years: OR 2.7, 95% CI 1.6, 4.7). DISCUSSION/SIGNIFICANCE OF IMPACT: Despite being at higher risk of infertility, cancer survivors may still be at considerable risk of unintended pregnancy. Women with certain types of cancer that are more likely to be hormone responsive, such as some types of breast cancer, may be hesitant to use hormonal birth control and thus be at higher risk of unintended pregnancy. Counseling for cancer survivors should include a discussion of the risk of unintended pregnancy and contraceptive options.

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Effect of omalizumab for autoimmune progesterone dermatitis refractory to bilateral oophorectomy: a case report

Allergy Asthma & Clinical Immunology ◽

10.1186/s13223-021-00561-2 ◽

2021 ◽

Vol 17 (1) ◽

Author(s):

Akshay Varghese ◽

Terri Paul ◽

Harold Kim ◽

Stan Van Uum ◽

Peter Vadas ◽

...

Keyword(s):

Menstrual Cycle ◽

Luteal Phase ◽

Oral Prednisone ◽

Menopausal Symptoms ◽

Treatment Modalities ◽

High Dose ◽

Type I ◽

Bilateral Oophorectomy ◽

First Case ◽

Dose Oral

Abstract Background Autoimmune progesterone dermatitis (APD) is a rare skin condition caused by sensitivity to high levels of progesterone secreted during the luteal phase of the menstrual cycle. This may be due to various pathophysiological mechanisms including a Type I and Type IV hypersensitivity reaction. Here we present the case of a patient with APD whose episodic flares were controlled by the addition of omalizumab, after a bilateral oophorectomy failed to resolve her symptoms. Case Presentation A 34-year-old female presented to our Endocrine clinic with marked Cushingoid features secondary to high-dose oral prednisone prescribed for APD diagnosed 6 years earlier. She first developed a pruritic maculopapular rash on her arms and legs just after the birth of her second child in 2009. The rash was also associated with headaches and diffuse angioedema. Symptoms occurred for 1–2 weeks, in a cyclical fashion, during the luteal phase of each menstrual cycle and subsided within a few days after menses. The severity of symptoms increased as time went on, and flare-ups began to also include dyspnea, nausea, vomiting and abdominal pain. Her symptoms improved with administration of oral prednisone, but she continued to experience breakthrough symptoms. After multiple failed treatment modalities, she elected bilateral oophorectomy in 2018. However, her symptoms of APD persisted and she still required high-dose oral prednisone. Her condition was further complicated by vasomotor menopausal symptoms and progressive iatrogenic Cushing’s syndrome. She eventually was started on Omalizumab, which suppressed further recurrences of APD symptoms and allowed her to wean off prednisone. Vasomotor menopausal symptoms responded well to the addition of conjugated estrogens with bazedoxifene. However, her symptoms of diffuse bony pain and arthralgias which started whilst on prednisone have persisted in spite of discontinuing prednisone. Conclusions To our knowledge, this is only the third case of APD which was successfully treated with Omalizumab and the first case where a bilateral oophorectomy failed to resolve symptoms of APD in the literature. This case also demonstrates the complications of vasomotor menopausal symptoms secondary to a bilateral oophorectomy, as well as the adverse effects of long-term glucocorticoid therapy.

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