Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Behaviors and Mental Disorders

Neoplasms

Gland and Hormone Related Diseases

Rare Diseases

Premature Birth

Cognitive Dysfunction

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Primary Ovarian Insufficiency

Menopause, Premature

Cognition Disorders

Neurocognitive Disorders

Mental Disorders

Psychotic Disorders

Ovarian Cancer

Quality of Life

Ovarian Epithelial Cancer

Menopause

* RRSO before the age of 45 years
* RRSO was done 10 or more years ago

* Natural menopause ≥ 50 years of age
* No RRSO ≤ age of 55
* No treatment-induced menopause ≤ 50 years of age

Testing for possible unfavourable health effects of early surgical menopause

CAC-score

Flora E van Leeuwen, Phd

Risk-Reducing Salpingo-Oophorectomy (RRSO) at the age of 35 to 45 years is recommended for women with a high genetic risk for ovarian cancer. While this procedure decreases the risk of ovarian cancer by 80-96%, it also results in an immediate menopause. Current research on potential adverse effects of premenopausal risk-reducing salpingo-oophorectomy, such as increased risk of cardiovascular disease, compromised bone health, cognitive dysfunction and reduced quality of life, is limited, mostly due to short follow up.

The investigators will conduct a multicenter cross-sectional study nested in a cohort of BRCA mutation carriers from 8 Dutch centers for hereditary cancer. Eligible participants are women who underwent RRSO before the age of 45. The participants will be frequency-matched on current age with women above the age of 55 without RRSO or with RRSO after the age of 55. Participants will complete an online questionnaire containing various questions about lifestyle, medical history, risk factors for cardiovascular disease, bone health, cognition and quality of life. Participants will be asked to visit one of the participating hospitals for a blood test, a cardiovascular assessment and a DEXA scan for determining bone mineral density. Afterwards participants will be requested to perform the online Amsterdam Cognition Scale.

Rationale: Women at high genetic risk of ovarian cancer are advised to undergo risk-reducing salpingo-oophorectomy (RRSO) at ages 35-45 years. Currently, in the Netherlands \~500 women/ year opt for RRSO, which minimizes ovarian cancer risk and may decrease breast cancer (BC) risk as well, due to reduced gonadal hormone levels. Besides favorable effects of RRSO on ovarian cancer and, potentially, BC risk, RRSO induces immediate menopause, which may have unfavorable long-term health consequences. Early menopause has been associated with increased risks of cardiovascular disease (CVD), lower bone mineral density (BMD), cognitive impairment, and decreased quality of life. Current evidence regarding these health effects is mainly based on women with a natural early menopause, and it is unknown whether these results hold for women undergoing RRSO at early premenopausal ages.

Objective: The investigators will investigate long-term health effects of premenopausal RRSO on (subclinical) cardiovascular status, BMD, cognition and quality of life.

Study design: the investigators will assess long-term health effects of RRSO in a cross-sectional study, among 500 women who underwent premenopausal RRSO compared to 250 women of the same age without RRSO (or with RRSO after age 55). Eligible women will be invited to participate in a screening program assessing cardiovascular status, bone mineral density, cognitive functioning and quality of life.

Study population: Women are eligible for the premenopausal RRSO group if:

* RRSO before the age of 45 years;
* RRSO was done 10 or more years ago; Women are eligible for the comparison group without premenopausal RRSO if the participant did not undergo RRSO before the age of 55 years, and did not have a natural or therapy induced menopause before age 50.

Primary study outcome: To study long-term effects of premenopausal RRSO on:

* (subclinical) CVD
* BMD
* Cognition

Secondary study outcome: To study long-term effects of premenopausal RRSO on:

* Quality of life
* Urogenital problems
* Cardiovascular risk factors

Furthermore, the investigators will examine the influence of age at RRSO, time since RRSO, hormone replacement therapy (HRT), carrier ship of a BRCA1 or BRCA2 mutation and BC history on the outcome.

The obtained knowledge will assist physicians in counselling women with high ovarian cancer risk and help them to make well-informed decisions.

Optional for studyparticipants is to collect and store DNA in a blood Biobank.

In order to be eligible the ovaries have been removed.

Health After eaRly Menopause Due to Oophorectomy

Favourable and Unfavourable Health Effects of Risk-Reducing Salpingo-Oophorectomy in Women With a High Genetic Risk of Ovarian Cancer

we will study the effect of RRSO on BC, contralateral breast cancer and ovarian cancer risk and prognosis after BC/ovarian cancer

Due to the lack of estrogen we expect more atherosclerotic diseases.

Loss of estrogen can result in more activity of osteoclasts and less activity of osteoblasts, The DXA-scan is corrected for age, with lower values representing a worse outcome

Loss of estrogen can result in more activity of osteoclasts and less activity of osteoblasts

There are some studies suggesting that an early menopause has an influence on cognition

How do women with a premenopausal RRSO experience their life. The SF-36 questionnaire ranges from 36 to 149, with higher values representing a worse outcome

How do women with a premenopausal RRSO experience their life. We measure the body image using the EORTC QLQ BR23, with ranges from 2 to 8, with higher values representing a worse outcome

How do women with a premenopausal RRSO experience their life. The FACT-ES questionnaire ranges from 0 to 76, with higher values representing a worse outcome

Have women with a premenopausal RRSO more urogenital complaints due to longer duration of estrogen deficiency.

The SAQ questionnaire scale has questions with different weights as described in Thirlaway et al. 1996

Have women with a premenopausal RRSO more urogenital complaints due to longer duration of estrogen deficiency.

The UDI-6 questionnaire scale has a range from 0 to 18, with higher values representing a worse outcome

Have women with a premenopausal RRSO more urogenital complaints due to longer duration of estrogen deficiency.

The IIQ-7 questionnaire scale has a range from 0 to 24, with higher values representing a worse outcome

Are some risk factors for cardiovascular disease more prevalent in women with a premenopausal RRSO

Dutch Cancer Society

Erasmus Medical Center

Radboud University Medical Center

The Netherlands Cancer Institute

Symptoms and General Pathology

Syndrome

Infertility

Polycystic Ovary Syndrome

Pregnancy Complications

Urogenital Diseases

Female Urogenital Diseases

Female Urogenital Diseases and Pregnancy Complications

Cysts

Ovarian Cysts

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Gonadal Disorders

Endocrine System Diseases

All Drugs and Chemicals

Hormones

WING IU LI

PUI WAH JACQUELINE CHUNG

PUI WAH JACQUELINE CHUNG, MBBS

KAREN NG, MBBS

NGA PING PATRICIA IP, MBBS

This study aims to assess the association of Anti-Müllerian hormone (AMH) with polycystic ovarian syndrome, premature ovarian insufficiency and fertility. The main objectives include the following:

1. To study the level of serum AMH in women with PCOS and to evaluate the utility of serum AMH in the diagnosis of PCOS.
2. To evaluate the level of serum AMH in women with POI and to evaluate the utility of serum AMH in the management of POI.
3. To evaluate the associations of basal AMH level with FSH level and AFC respectively for women undergoing ART treatment.
4. To determine the optimal regimen of gonadotropin for ovarian stimulation for women undergoing ART treatment.
5. To evaluate the predictive value of serum AMH in reproductive outcomes including oocyte quality, embryo quality, pregnancy loss, clinical pregnancy and live birth rate in women undergoing ART treatment.

\[Background\] Anti-Müllerian hormone (AMH), which level can be assessed in serum, is a product of follicular granulosa cells of preantral and small antral follicles in the ovary. AMH expression increases prior to follicle-stimulating hormone (FSH)-dependent selection (follicles up to 8 mm) and rapidly decreases thereafter (follicles \> 8 mm. Thus, serum AMH level is a reliable marker of functional ovarian reserve as it reflects the pool of growing follicles. Since AMH is relatively cycle independent and has no inter-rater variability, it is considered to be a more reliable biomarker of ovarian function across an array of clinical conditions when compared with follicle-stimulating hormone (FSH) and antral follicular count (AFC).

\<Association between AMH and polycystic ovarian syndrome (PCOS)\> PCOS is a common endocrine disorder that causes menstrual irregularity and hyperandrogenism in women. It affects approximately 4-20% of women of reproductive age. Women with PCOS have been shown to have elevated AMH levels when compared with women without PCOS as there is an increased number of ovarian follicles in PCOS. Therefore, AMH is being increasingly recognised as a marker for the diagnosis of PCOS. However, a specific cutoff value is yet to be determined. When the issue is addressed, serum AMH levels could potentially replace ultrasound in the diagnosis of PCOS as ultrasound is more costly and less accessible.

\<Association between AMH and premature ovarian insufficiency (POI)\> POI is defined as the cessation of ovarian function before the age of 40 years. Timely diagnosis is important in order to appropriately counsel and treat the patients with POI.

Prompt initiation of hormone replacement therapy is vital to minimise the risk of long-term health complications including osteoporosis and premature cardiovascular disease. AMH levels were significantly low to undetectable in women with POI. Since AMH is independent of the timing in a menstrual cycle, the measurement may be beneficial in the phase of menstrual irregularity and could potentially help to assess the progression of ovarian senescence.

\<Associations between AMH and Fertility\> Serum AMH level is an important indicator of women's ovarian reserve and a crucial tool in assisted reproductive technology (ART) for the evaluation of women's fertility. A recent systematic review concluded that basal serum AMH is a strong pretreatment predictor of poor response to controlled ovarian stimulation (COS) and correlates with the risk of ovarian hyperstimulation syndrome. As such, clinicians can individualise the stimulation protocols to optimise the ovarian response. In addition, AMH-based prognostication counselling can be provided to patients with realistic expectation regarding the ART outcomes.

Ovarian reserve has a well-established positive correlation with pregnancy outcome. However, current evidence of AMH in the prediction of reproductive outcome following ART treatment remains controversial. Therefore, there is a need to study the predictive value of AMH on pregnancy outcome in women undergoing ART.

\[Hypothesis\]

1. Serum AMH level is elevated in women with PCOS.
2. Serum AMH level is very low or undetectable in women with POI.
3. Serum AMH level has a significant correlation with FSH and AFC in women undergoing ART treatment.
4. Serum AMH level can predict reproductive outcomes following ART treatment.

\[Study design\] This is a prospective observational study.

\[Methods\] Investigators will collect data from patients who undergo management for PCOS and POI in the Department of Obstetrics and Gynaecology at the Prince of Wales Hospital from 2022 to 2026. For patients undergoing investigation of PCOS and POI, routine venous blood tests for AMH and hormonal profile including FSH, luteinizing hormonal (LH), oestradiol (E2) levels will be obtained. For patients undergoing ART treatment, routine venous blood tests for AMH and hormonal profile, and transvaginal ultrasound for AFC will be arranged to assess the patients' ovarian reserve prior to the commencement of treatment. Patients will be recruited and consent will be obtained for the storage of any remaining serum from the blood tests. The stored blood samples will then be retrieved for this study.

\[Data processing and analysis\] Data analysis will be performed using the Statistical Packages of Social Sciences for Windows (SPSS, Inc). Data will be presented by percentage, mean and standard deviation, and median where appropriate. Comparisons between groups will be carried out by Student T test/Mann-Whitney U test for continuous variables and Chi-square/Fisher's exact test for categorical data. Two-tailed P\<0.05 will be considered significant.

\[Sample size\] All patients fulfilling the inclusion criteria attending the Department of Obstetrics and Gynaecology at the Prince of Wales Hospital from 2022 to 2026 will be recruited. The sociodemographic records of the participants including their menstrual history, routine hormonal results, ovarian reserve assessment and ultrasound assessment of AFC will be obtained. Metabolic screening results and ART treatment records and subsequent laboratory and reproductive outcome will be obtained if necessary.

Clinical Application of Serum Anti-Müllerian Hormone (AMH) Measurements

To evaluate the serum AMH level of women who undergo investigation for polycystic ovarian syndrome (PCOS), premature ovarian insufficiency (POI) or subfertility

To assess the type of gonadotropin used for ovarian stimulation for women undergoing ART treatment

To assess the total gonadotropin dose used for ovarian stimulation for women undergoing ART treatment

To evaluate the number of oocytes retrieved during oocyte retrieval for women undergoing ART treatment

To evaluate the serum FSH level of women who undergo ART treatment

To evaluate the serum LH level of women who undergo ART treatment

To evaluate the serum estradiol level of women who undergo ART treatment

To evaluate the AFC of women who undergo ART treatment

To assess for the presence of gestational sac using ultrasonography after embryo transfer procedure for women undergoing ART treatment

To assess whether live babies are born after women receive ART treatment

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Health After eaRly Menopause Due to Oophorectomy	NCT03835793	Surgical Menopa... BRCA1 Mutation BRCA2 Mutation Cardiovascular ... Bone Mineral De... Cognitive Decli... Quality of Life Menopause Surgi...	CAC-score	55 Years -	The Netherlands Cancer Institute
Clinical Application of Serum Anti-Müllerian Hormone (AMH) Measurements	NCT05858307	Anti-Müllerian ... Polycystic Ovar... Premature Ovari... Fertility Issue...		10 Years - 44 Years	Chinese University of Hong Kong

Spots Global Cancer Trial Database for premature ovarian insufficiency