Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Gland and Hormone Related Diseases

Premature Birth

Primary Ovarian Insufficiency

Menopause, Premature

Menopause

All Drugs and Chemicals

Vasoconstrictor Agents

Respiratory System Agents

Reproductive Control Agents

Hormones

Epinephrine

Racepinephrine

Epinephryl borate

Contraceptive Agents

Contraceptives, Oral

Alkylating Agents

* Prior exposure to alkylating agent chemotherapy and/or radiation therapy
* At least 1 year from completion of chemotherapy and/or radiation therapy
* Uterus and at least one ovary are present
* Not pregnant or breastfeeding in the past 3 months
* Not taking any hormones or oral contraceptives for at least 4 weeks prior to study visits
* No medical condition (other than cancer) known to be associated with premature ovarian failure (such as Turner's Syndrome or Fragile X) or ovulatory dysfunction (such as thyroid disease, congenital adrenal hyperplasia, Cushing's syndrome, hyperprolactinemia, and polycystic ovary syndrome).

* Never exposed to chemotherapy or radiation therapy
* Regular menstrual cycle (every 21-35 days)
* Uterus and at least one ovary are present
* Not pregnant or breastfeeding in the past 3 months
* Not taking any hormones or oral contraceptives for at least 4 weeks prior to study visits
* No medical condition known to be associated with premature ovarian failure (such as Turner's Syndrome or Fragile X) or ovulatory dysfunction (such as thyroid disease, congenital adrenal hyperplasia, Cushing's syndrome, hyperprolactinemia, and polycystic ovary syndrome).

Clarisa R Gracia, MD, MSCE

Hypothesis: Girls and women exposed to chemotherapy and/or radiation therapy experience endocrine changes more similar to women in their late reproductive years than to same-age peers. These changes will be more dramatic in women who receive high dose therapy compared to women who receive low dose therapy.

At annual visits over 3-5 years, a combination of physical exam, medical history, menstrual diary keeping, pelvic ultrasound and blood hormones tests will be used to measure "ovarian reserve" , that is the number and quality of the eggs that remain in the ovaries. The study will also try to learn if those who received higher doses of certain chemotherapies are more likely to have changes in these tests sooner than those women who received smaller doses of these same drugs. Additionally a DNA (deoxyribonucleic acid) sample will be collected to look for gene variations that may predict susceptibility to ovarian damage from cancer treatments. Information learned from this study may help researchers to develop guidelines to identify problems with a female cancer survivor's ovaries before irregular menses or other symptoms of ovarian failure occur.

Up to 400 females will participate in this study in one of three cohorts:

* 150 females ages 11-35, with history of exposure to alkylating agent chemotherapy and/or radiation therapy
* 150 Unexposed peers, ages 11-35, never exposed to chemotherapy or radiation therapy
* 100 Unexposed females, ages 40-50 never exposed to chemotherapy or radiation therapy

Assessing Fertility Potential in Female Cancer Survivors

Data will be shared with Dr. Jill Ginsberg, a co-investigator of the study.

Primary Outcomes for this study will include mean and changes in reproductive hormone measures obtained during the early follicular phase of the menstrual cycle (days 1-4).

All ovarian follicles and cysts will be measured by transvaginal or transabdominal ultrasound. Follicles will be measured in millimeters and grouped according to size: 2-5 mm, 6-9 mm, and \>10 mm in diameter.

Children's Hospital of Philadelphia

University of Pennsylvania

Otherwise healthy, mid-reproductive aged women between the ages of 20 and 35 years previously exposed to high dose alkylating agent therapy (or have an alkylator score of 1 or more), and at least 1 year from cancer treatment.

Healthy, mid-reproductive aged women between the ages of 20 to 35 who have not been exposed to cancer therapy.

Reproductive aged women between the ages of 43-50 who have not been exposed to cancer therapy, nor have a history of infertility

Women of late to mid reproductive age may participate in a study using novel methodology to identify subtle changes in the reproductive endocrine axis via daily urine hormone analysis, which may have important implications for reproduction and may signal reproductive senescence.

Women with a reduced follicular pool either from natural aging or previous chemotherapy, may not have any clinical signs or symptoms and traditional measures of ovarian reserve, such as basal Follicle Stimulating Hormone may be within the normal range. However, there may be alterations in the luteal or follicular phases(shortened follicular phase and luteal insufficiency) due to compromised follicle competency and alterations in the H-P-O axis. Therefore this aim uses novel methodology to identify subtle changes in the reproductive endocrine axis which may have important implications for reproduction and may signal reproductive senescence. Compared to yearly follicular measures of reproductive hormones, daily urine hormone analysis provides a more integrative assessment.

Three groups of subjects will be recruited:

Group 1: Otherwise healthy, mid-reproductive aged women between the ages of 20 and 35 years previously exposed to high dose alkylating agent therapy (or have an alkylator score of 1 or more), and at least 1 year from cancer treatment.

Group 2: healthy, mid-reproductive aged women between the ages of 20 to 35 who have not been exposed to cancer therapy.

Group 3: healthy, late reproductive aged women between the ages of 43-50 who have not been exposed to cancer therapy, nor have a history of infertility.

Subjects in all groups must have regular menstrual cycles every 21-35 days, and have a uterus and both ovaries. Each participant will complete daily urinary collections for 2 menstrual cycles to assess reproductive hormones. The ultimate goal of this work is to better estimate the reproductive window, or time to menopause.

daily urinary collections for 2 menstrual cycles

Assessing Urinary Hormones in Female Cancer Survivors

Follicular and Luteal Dysfunction in Cancer Survivors

Integrated urinary follicular-phase Follicle Stimulating Hormone (FSH) in urine samples collected daily for 2 menstrual cycles will be measured in mIU/mL by means of two-site chemiluminescent immunoassay with the use of two monoclonal antibodies.

Integrated urinary follicular-phase Luteinizing Hormone (LH) in urine samples collected daily for 2 menstrual cycles will be measured in mIU/mL by means of two-site chemiluminescent immunoassay with the use of two monoclonal antibodies.

Estrone Conjugate (E1C) in urine samples collected daily for 2 menstrual cycles will be measured in ug/dL by means of E1C immunoassay.

Pregnanediol-glucuronide (PDG) in urine samples collected daily for 2 menstrual cycles will be measured in ug/mL by means of PDG immunoassay.

Urinary Creatinine in urine samples collected daily for 2 menstrual cycles will be measured in mg/mL by means of spectrophotometric assay.

Participants will be provided with calendars on which to record detailed menstrual cycle information during the study. The total menstrual cycle length will be defined as the number of days from day 1 of menses to the day before the next menses. The Kassam method will be used to determine evidence of luteal activity, presumably ovulation. Follicular phase will be defined as the number of days from day 1 of menses up to the day of luteal transition and the luteal phase length will be defined as the number of days beginning from the day after the day of luteal transition to the day before the next menses.

Neoplasms

Skin and Connective Tissue Diseases

Leiomyoma

Myofibroma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neoplasms, Connective Tissue

Connective Tissue Diseases

Antineoplastic Agents

Letrozole

Aromatase Inhibitors

Enzyme Inhibitors

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormone Antagonists

All consenting patients will be started on Letrozole at a dose of 2.5 mg/day for 8 weeks.

Letrozole at a dose of 2.5 mg/day for 8 weeks.

Letrozole (aromatase inhibitor)

Anwar H Nassar, MD

Fibroids are benign tumors that might results in bleeding. Surgery is their definitive treatment. Some medical therapies have been tried for women who wish to preserve their uterus. Recent reports have demonstrated a role for a new category of drugs called aromatase inhibitor (such as Femara) in the treatment of fibroids. This study is conducted to assess the effect of Femara (letrozole) on the size of fibroids in women around menopause.

Fibroids (leiomyomas) are benign tumors that originate in the musculature of the uterus. They are the most common cause for removal of the uterus in women. Surgery is the final definitive treatment of fibroids. However, surgery is relatively risky. Hence, a few medical therapies have been tried for women who wish to preserve their uterus. However, most of those therapies have side effects that prohibit their routine use. Recent reports have demonstrated a role for a new category of drugs called aromatase inhibitor ( such as Femara) in the treatment of fibroids. To the best of our knowledge, this drug has not been studied yet in the management of fibroid of the uterus apart from one case report.

The objective of the current study is to assess the effect of aromatase inhibitors, specifically Femara (letrozole) on the size of fibroids in women around menopause. We are hoping that by decreasing their size, we could avoid having patients undergo surgery. The data generated is invaluable in that sense.

Aromatase Inhibitors for Treatment of Uterine Leiomyomas

Aromatase Inhibitors for the Prevention of the Growth of Uterine Leiomyomas in Perimenopausal Women: A Pilot Study

American University of Beirut Medical Center

Anwar Nassar, MD/Associate Professor

Infertility

Infertility, Female

Postmenarchal female cancer patients scheduled to undergo cancer therapy may enroll in this study to assess changes in existing and novel surrogate measures of fertility potential before, during and after chemotherapy. Measures of fertility potential to be tested include ultrasound imaging for antral follicle counts and ovarian volumes, endocrine evaluation, and assessment of oxidative stress.

Eligible women are asked to complete a structured interview, questionnaires, a monthly menstrual diary, a brief physical examination, a blood test, and an abdominal or pelvic ultrasound at baseline and at 3 month intervals following start of chemotherapy through 6 months post end of treatment.

Within subject changes in continuous variables (hormones, urinary isoprostane levels, ovarian volume, AFC) will be compared using paired t-tests (nonparametric tests as appropriate). Non-Gaussian-distributed variables will be logarithmically transformed prior to analysis. In general, changes from baseline to every 3 month assessment will be compared individually as well as changes from baseline to post treatment. In addition, regression models for repeated measures will be used to describe the pattern of change in these outcomes over time. Additional models will be constructed to adjust for potential confounding variables including age, chemotherapy type, dose and duration of treatment, radiation treatment, gonadotropin releasing hormone agonist use, and hormone use. Finally, regression models will be used to evaluate the association between changes in urinary isoprostane levels over the study with changes in endocrine measures.

The Longitudinal Ovarian Reserve Study

The Effects of Cancer Treatment on Ovarian Function: A Longitudinal Study by the Oncofertility Consortium

20 mls blood will be obtained at stated timepoints for determining levels of Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), Estradiol (E2), Inhibin B, and Anti-mullerian Hormone (AMH). In menstruating girls and young women hormone measures will be obtained during the early follicular phase of the menstrual cycle (days 1-4). In women with irregular cycles the testing will be done spontaneously without regard for the bleeding pattern.

Ovaries will be measured in three dimensions. Uterine size and endometrial thickness will also be performed. The transvaginal approach is preferred, but transabdominal ultrasound will be performed in girls who do not feel comfortable with the transvaginal procedure.

Antral Follicle Counts by size (2-5 mm, 6-9 mm, and \>9 mm in diameter) will be determined.

24 hour urine collection will be analyzed to assess urinary 8,12-iso-iPF2alpha-VI isoprostane levels.

Subjects are asked to document menstrual bleeding in a diary, noting duration of each menstrual period in days, bleeding intensity (spotting, light, moderate, heavy, flooding, none), and intervals between periods.

The validated "Menopausal Symptom List" (MSL) will be used at each study visit to assess the presence or absence of menopausal symptoms during the past month, the frequency and severity of each symptom. Symptoms captured include: hot flashes, vaginal dryness, concentration/memory problems, irritability, mood swings, feeling sad, feeling anxious, trouble sleeping, aches, joint pain, headaches.

One of two well validated and widely used questionnaires will assess Quality of Life measures: For adolescents 20 years of age or younger, the Minneapolis-Manchester Quality of Life (MMQL) - Adolescent Form will be administered. This questionnaire assesses demographics, physical functioning, cognitive functioning, psychological functioning, body image, social functioning, outlook on life, and intimate relations in cancer survivors. The MMQL is a 46 item validated, standardized self-report instrument designed to assess health related quality of life in adolescent survivors of cancer.

Subjects over 20 years of age will be asked to complete a self report quality of life questionnaire entitled Assessing Quality of Life in Adult Cancer Survivors (QLACS). This questionnaire has been proven to be valid and reliable for comparing quality of life in adult cancer survivors and non-cancer patients.

Infections

Symptoms and General Pathology

Communicable Diseases

Papillomavirus Infections

Disease Attributes

Sexually Transmitted Diseases

Sexually Transmitted Diseases, Viral

Virus Diseases

DNA Virus Infections

Tumor Virus Infections

Genital Diseases

Urogenital Diseases

Anti-Infective Agents

Interferons

Interferon-alpha

Interferon alpha-2

Antiviral Agents

Immunologic Factors

Vaginal placement of human interferon alpha 2b vaginal effervescent capsules, one pill a day daily, 10 days, for a course of treatment, a total of 3 courses

promestriene cream vaginal medication, once a day, 1g each time, 10 days, for a course of treatment, a total of 3 courses of treatment

given one human interferon alpha 2b vaginal effervescent capsule vaginal placement + promestriene cream 1g vaginal medication, once a day, for 10 days, for a course of 1, 3 courses of continuous use.

①Interferon group: human interferon alpha 2b vaginal effervescent capsule vaginal medication. ② Promestriene group: promestriene cream vaginal medication. ③Interferon + promestriene combination group: two drugs were given in combination.

Human interferon alpha 2b vaginal Effervescent capsules

Cui Yingying, doctorate

A randomized controlled study was conducted to determine the effects of vaginal estrogen and human interferon alpha 2b vaginal effervescent capsules on vaginal microecology in perimenopausal and postmenopausal women. To determine whether there is a synergistic effect between the two in the treatment of HPV infection in perimenopausal and postmenopausal women. To observe the effects of two drugs alone and combined on the vaginal immune environment of patients.

After pre-enrollment screening, patients who met the inclusion criteria signed informed consent and were divided into interferon group, promestriene group and interferon + promestriene combination group according to the randomized controlled number table.

① Interferon group: human interferon alpha 2b vaginal effervescent capsules were given vaginal medication, one capsule a day for 10 days, for a course of treatment, a total of 3 courses of treatment. ② Promestriene group: Promestriene cream vaginal medication, once a day, 0.1g each time, 10 days, for a course of treatment, a total of 3 courses of treatment. ③Interferon + promestriene combination group: interferon 1 grain + promestriene cream 0.1g, vaginal medication, once a day, continuous use for 10 days, for a course of treatment, continuous use of 3 courses of treatment. Vaginal secretions were collected before treatment and one week after treatment to detect vaginal microecology. Flow cytometry was used to detect the proportion of immune cells in vaginal secretion. ELISA was used to detect immune-related cytokines (IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10) in vaginal secretions.

HPV was reviewed at 1 month and 1 year after drug cessation.

Treatment of HPV Infection in Perimenopausal and Postmenopausal Women

Therapeutic Effect of Topical Estrogen and Human Interferon Alpha 2b Vaginal Effervescent Capsules in Perimenopausal and Postmenopausal Women With High-risk HPV Infection

Number of cases of HPV negative conversion after medication/total cases ×100%

Concentration and diversity of vaginal microflora after drug treatment

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Assessing Fertility Potential in Female Cancer Survivors	NCT01143844	Effects of Chem...		11 Years - 50 Years	University of Pennsylvania
Assessing Urinary Hormones in Female Cancer Survivors	NCT03197532	Effects of Chem...		20 Years - 50 Years	University of Pennsylvania
Aromatase Inhibitors for Treatment of Uterine Leiomyomas	NCT00945360	Symptomatic or ...	Letrozole (arom...	50 Years - 55 Years	American University of Beirut Medical Center
The Longitudinal Ovarian Reserve Study	NCT02395341	Effects of Chem...		15 Years - 45 Years	University of Pennsylvania
Assessing Fertility Potential in Female Cancer Survivors	NCT01143844	Effects of Chem...		11 Years - 50 Years	University of Pennsylvania
Treatment of HPV Infection in Perimenopausal and Postmenopausal Women	NCT05863975	HPV Infection	Human interfero...	45 Years - 60 Years	Qianfoshan Hospital
Treatment of HPV Infection in Perimenopausal and Postmenopausal Women	NCT05863975	HPV Infection	Human interfero...	45 Years - 60 Years	Qianfoshan Hospital

Spots Global Cancer Trial Database for perimenopause