Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

All Conditions

Symptoms and General Pathology

Polycystic Ovary Syndrome

Abortion, Spontaneous

Ovarian Diseases

Syndrome

Pregnancy Complications

Urogenital Diseases

Female Urogenital Diseases

Female Urogenital Diseases and Pregnancy Complications

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Gonadal Disorders

Endocrine System Diseases

Cysts

Ovarian Cysts

Antineoplastic Agents

All Drugs and Chemicals

Reproductive Control Agents

Letrozole

Estradiol 17 beta-cypionate

Estradiol 3-benzoate

Estradiol

Polyestradiol phosphate

Dydrogesterone

Progesterone

Estrogens

Hormones

Hormone Antagonists

Aromatase Inhibitors

Enzyme Inhibitors

Estrogen Antagonists

Estrogen Receptor Antagonists

Progestins

Polycystic ovarian disease (PCOS) women undergoing frozen embryo transfer (FER) will use Letrozole 5 mg starting on day 3 of spontaneous menstrual period or after progesterone withdrawal bleeding for five consecutive days.

PCOS women will use daily Cetorelix acetate 0.25 mg injections for 5 days from day 1-3 of the menstrual follow or after progesterone (P4) withdrawal bleeding. They will commence daily oral Estradiol Valerate (E2) 2 mg twice daily for 5 days starting from day 3 of the menstrual flow or after P4 withdrawal bleeding, then-after three times daily. When endometrial thickness reaches 7 mm or more, the dose of E2 will be reduced to 4 mg/ day. Women will start using vaginal micronized P4 100 mg three times daily starting from 8PM. After 48 hours of starting the vaginal P4, oral Dydrogesterone 10 mg three times daily will commence.

Letrozole 5 mg starting on day 3 of spontaneous menstrual period or after progesterone withdrawal bleeding for five consecutive days.

Letrozole 2.5mg

One of the indications of freezing is to reduce the risk of ovarian hyperstimulation syndrome particularly in polycystic ovarian disease (PCOS) women. Very few RCTs addressed the issue of optimizing the endometrium for a frozen cycle. Interestingly, Letrozole for ovarian stimulation showed significantly better reproductive outcome when compared with hormone replacement therapy (HRT) cycle. In addition, HRT cycle has been associated with higher miscarriage rate when compared with natural cycle frozen embryo transfer. Nevertheless, there is not yet a well-designed prospective randomized study comparing letrozole and HRT in PCOS women undergoing frozen embryo transfer.

Freezing oocytes and embryos has become an integral part of the daily IVF practice. One of the indications of freezing is to reduce the risk of ovarian hyperstimulation syndrome particularly in polycystic ovarian disease (PCOS) women.

Very few randomized control trials addressed the issue of optimizing the endometrium for a frozen cycle. As PCOS women do not regularly ovulate, most of their frozen cycles are conducted after hormonal replacement therapy (HRT) preparation of the endometrium or after ovulation induction. In HRT cycle the endometrium is prepared using exogenous estradiol and progesterone. While HRT cycles requires less monitoring and easy scheduling, it is costly, associated with increased risk of thrombosis and women must continue using the exogenous hormones up to 10 to 12 weeks of gestation.

Interestingly, Letrozole for ovarian stimulation showed significantly better reproductive outcome when compared with HRT cycles. In agreement with the previous Chinese study, a retrospective Japanese ART registry data that included 110 722 frozen cycles confirmed the superiority of letrozole. Nevertheless, there is not yet a well-designed prospective randomized study.

In addition, HRT cycle has been associated with higher miscarriage rate when compared with natural cycle frozen embryo transfer. HRT is usually used in patients with PCOS. A retrospective study including 2664 PCOS patients showed significant decrease in the pregnancy loss when letrozole was used when compared with HRT in frozen cycles.

Investigators thought of comparing letrozole and HRT in women with PCOS who are undergoing frozen cycles in PCOS women. Live birth and miscarriage rates will be the primary outcomes.

Letrozole Versus Hormonal Preparation in Frozen Cycles of PCOS Patients.

Letrozole Versus Hormonal Preparation in Frozen Cycles of PCOS Patients. Randomized Controlled Study

A birth after 24 weeks gestation with a baby showing signs of life.

loss of pregnancy before 24 weeks gestation

ongoing viable pregnancy (by ultrasound examination at 12 weeks' gestation)

Dubai Fertility Center

Principal investigator

Skin and Connective Tissue Diseases

Leiomyoma

Infertility

Myofibroma

Endometriosis

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Alan H DeCherney, M.D.

This study was designed to allow inpatient and outpatient evaluation of women with a variety of reproductive and endocrine-related disorders for purposes of research and physician education.

The evaluations may include ultrasound examinations, blood, saliva, and/or urine samples. In some cases, specific laboratory or X-ray studies will be performed to confirm the diagnosis or assist in the treatment of the patient. These additional tests will be conducted within the guidelines of current gynecologic practice. In some cases, the patient will receive medical or surgical treatment for their disorder.

The purpose of this study is to provide an opportunity for physicians to evaluate women with medical conditions of reproduction. These evaluations and treatments will support clinical training and research for the accredited training program in reproductive endocrinology at the National Institute of Child Health and Human Development (NICHD).\<TAB\>

The specific objective of this protocol is to gain knowledge and collect data in order to allow for hypothesis generation in future research as well as give NICHD investigators and trainees hands on experience related to the diagnoses, management, treatment and follow-up of reproductive endocrine disorders. Such disorders include but are not limited to Polycystic ovarian syndrome, Endometriosis, Primary ovarian insufficiency, Recurrent pregnancy loss, Primary amenorrhea and Infertility. This information will be taken from standard medical care/procedures and follow up of patients and healthy volunteers. It allows investigation into the problems of these patients for the purpose of furthering general knowledge and teaching.

Evaluation of Women With Endocrine and Reproductive-Related Conditions

Evaluation of Women and Men With Endocrine and Reproductive-Related Conditions

To provide a mechanism for reproductive endocrine fellows and staff to evaluate woman with medical conditions of interest for fellow training and clinical training and education.

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Musculoskeletal Diseases

Nutritional and Metabolic Diseases

Heart and Blood Diseases

Digestive System Diseases

Breast Neoplasms

Osteoporosis

Coronary Artery Disease

Myocardial Ischemia

Coronary Disease

Heart Diseases

Ischemia

Colonic Neoplasms

Bone Diseases

Bone Diseases, Metabolic

Metabolic Diseases

Breast Diseases

Skin Diseases

Vascular Diseases

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Micronutrients

Bone Density Conservation Agents

Vitamins

Vitamin D

Cholecalciferol

Calcium

Calcium, Dietary

Trace Elements

Vitamin D3

Calciferol

hormone replacement therapy

estrogens

progestins

estrogen replacement therapy

diet, fat-restricted

calcium

vitamin D

dietary supplements

Ross Prentice

To address cardiovascular disease, cancer, and osteoporosis, the most common causes of death, disability, and impaired quality of life in postmenopausal women. The three major components of the WHI are: a randomized controlled clinical trial of hormone replacement therapy (HRT), dietary modification (DM), and calcium/vitamin D supplementation (CaD); an observational study (OS); and a community prevention study (CPS). On October 1, 1997, administration of the WHI was transferred to the NHLBI where it is conducted as a consortium effort led by the NHLBI in cooperation with the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Cancer Institute (NCI), and the National Institute on Aging (NIA).

BACKGROUND:

Prior to 1991, little research had focused on health issues unique to, or more common for, women. This was especially the case for studies of chronic diseases and their prevention in mature women. These conditions (coronary heart disease, cancer, and osteoporosis) are the leading causes of impairment of quality of life, morbidity, and mortality in post-menopausal United States women. The WHI, mandated by Congress, was established in 1991 by the National Institutes of Health and located in the Office of the Director (OD). The Clinical Coordinating Center for the clinical trial/observational study was funded in September 1992 and the 16 Vanguard Clinical Centers were funded in March 1993. The initial protocol was developed jointly by the Clinical Coordinating Center and the Program Office and was reviewed and approved by the Investigators Committee on April 20, 1993. Additional clinical centers were funded in 1994.

On October 1, 1997, administration of the WHI was transferred to the NHLBI where it is conducted as a consortium effort led by the NHLBI in cooperation with the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Cancer Institute (NCI), and the National Institute on Aging (NIA).

DESIGN NARRATIVE:

As has been described in the objective, the WHI has three major components: a randomized controlled clinical trial, an observational study, and a study of community approaches to developing healthful behaviors. Recruitment for the WHI began in September 1993 and ended in December 1998. Six clinical centers completed recruitment in January 1997. The remaining 34 centers completed recruitment in December 1998.

CLINICAL TRIAL COMPONENT

The clinical trial component consists of three subtrials: the hormone replacement trial, the dietary modification trial, and the calcium /vitamin D supplementation trial. Approximately 27,500 women aged 50 to 79 are participating in the HRT, which tests whether long-term HRT reduces coronary heart disease and fractures without increasing breast cancer risk. Women with a uterus were randomized to receive either estrogen plus progestin or a placebo. Progestin was added to protect women with a uterus from endometrial cancer. Women who have had a hysterectomy were randomized to receive either estrogen alone or a placebo. The estrogen plus progestin trial was stopped early on July 8, 2002 after an average follow-up of 5.2 years on the recommendation of the Data and Safety Monitoring Board. The estrogen alone study continued unchanged until March 2, 2004 when the NIH instructed participants to stop taking their study pills and to begin the follow-up phase of the study. . Participants in the estrogen alone study will be followed for eight to 12 years and have clinic visits every six months to assure safety and assess their health.

The dietary modification trial component studies the effect of a low-fat, high fruit, vegetable and grain diet on breast cancer, colorectal cancer and heart disease in 48,000 postmenopausal women. Participants are randomized to a comparison group which maintains usual dietary habits or to a dietary change group. Women in the dietary change group decrease their fat intake to 20 percent of total daily calories, increase fruit and vegetable consumption to five or more servings per day, and increase grains to six or more servings per day. Additionally, they monitor their food intake and attend nutrition group meetings to learn more about changing their diets in the first year. Thereafter they attend four meetings per year.

The calcium/vitamin D supplementation subtrial tests whether calcium and vitamin D supplements reduce the risk of hip and other fractures and colorectal cancer in postmenopausal women. Women in the hormone replacement therapy and the dietary modification trials are encouraged to join the calcium/vitamin D supplementation study. Approximately 45,000 postmenopausal women are randomized into one of two study groups. One group was randomly assigned to receive 1,000 mg of elemental calcium (as calcium carbonate) and 400 International Units of vitamin D₃daily. The second group received a matching placebo.

Women already taking calcium supplements can continue to take them. Participants will be followed for eight to 11 years and contacted by their clinical center every six months to assure their safety and assess their health.

Total number of trial participants in all three subtrials is 68,135.

OBSERVATIONAL STUDY

The several goals of the study include: to give reliable estimates of extent to which known risk factors predict heart disease, cancers, and fractures; to identify new risk factors for these and other diseases in women; to compare risk factors, presence of disease at the start of the study and new occurrences of disease during the WHI in all study components; and to create a future resource to identify biological indicators of disease, especially substances and factors found in blood. The study enrolled 93,726 postmenopausal women and will track them for an average of nine years. Participants fill out periodic health forms and visit the clinic three years after enrollment. They take no medication and do not change their health habits.

COMMUNITY PREVENTION STUDY

The community prevention study consists of 12 separate studies conducted at eight of the Centers for Disease Control and Prevention's (CDC) University-based Prevention Research Centers through a cooperative agreement between NIH and CDC. The 12 studies began in October 1995 and continue for an additional five years. The collaboration supports health promotion and disease prevention research and demonstration projects that are community-based and focus on healthy behaviors that prevent the major causes of death and disability and that promote health practices that lead to more effective public health interventions. Each project provides research dissemination and translation of findings into community interventions. Topics under study include: attitudes towards hysterectomy, oophorectomy, and surgical menopause among African Americans; reducing cardiovascular disease risk among Black women; environmental and policy interventions to increase physical activity among minority women ages 40 to 75; peer support intervention for cardiovascular disease risk among African American women, aged 40 and older; assessing the effectiveness of a brief medical-provider educational intervention for osteoporosis in minority women aged 40 and older; improving the delivery of diabetes care to women in minority groups; and assessment of moderate physical activity among women.

Women's Health Initiative (WHI)

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

National Cancer Institute (NCI)

National Institute on Aging (NIA)

National Heart, Lung, and Blood Institute (NHLBI)

Wounds and Injuries

Fractures, Bone

Hormone replacement therapy

Leif Mosekilde, Professor MD DrMedSc

Jens Erik Beck Jensen, MD PhD

Peder Charles, MD DrMedSc

Stig Pors Nielsen, MD DrMedSc

Henning Beck Nielsen, MD DrMedSc

Kim Brixen, MD PhD

Ole Helmer Sørensen, MD DrMedSc

Hypothesis: Use of hormone replacement therapy (HRT) decreases the incidence of fractures in early postmenopausal women.

The project was initiated in 1990, and the inclusion ended in 1993. A total of 2,016 early postmenopausal women were divided into two groups: The first group accepted randomisation to HRT or not, and the second group was allowed to choose HRT or not.

The study was not blinded. Main measurements were fracture risk over 20 years, changes in bone mineral density over 20 years, and side effects, mainly breast cancer.

Aim: To study the ability of hormone replacement early after menopause on risk of fractures and changes in bone mineral density, and side effects.

The project was designed as a comprehensive cohort trial. One group accepted randomisation, and was randomised to hormone replacement therapy (HRT) or not (no placebo used).

502 were randomised to HRT, and 504 were randomised to no HRT) One group was allowed to choose HRT or not. A total of 221 chose HRT, and 789 chose no HRT.

First line HRT was oral sequential oestradiol/norethisterone in women with intact uterus and oral continuous oestradiol in hysterectomised women.

The study was initiated in 1990, and inclusion ended in 1993.

Danish Osteoporosis Prevention Study

Karen Elise Jensen Foundation

Novo Nordisk A/S

LEO Pharma

Novartis

University of Aarhus

Women who present to the Internal Medicine Breast Cancer Clinic with breast cancer and who after discussion with the consulting surgeon and oncologist have agreed to undergo neoadjuvant chemotherapy or neoadjuvant hormone therapy.

Dietlind L. Wahner-Roedler, M.D.

In patients with breast cancer who undergo neoadjuvant chemotherapy or neoadjuvant hormone therapy molecular breast imaging (MBI) is an accurate test for assessing response rate to neoadjuvant therapy.

The investigators propose to evaluate Molecular Breast Imaging in patients undergoing neoadjuvant therapy for breast cancer with the aims to document that 1) the change in uptake of 99mTc-sestamibi prior to initiation of neoadjuvant therapy, after 3-5 weeks of neoadjuvant therapy and at completion of neoadjuvant therapy prior to breast cancer surgery will be a reflection of the tumor response to neoadjuvant therapy.

2) Tumor response at 3-5 weeks of neoadjuvant therapy is predictive of tumor response at completions of neoadjuvant therapy.

3) Post-neoadjuvant tumor size as determined by MBI corresponds to size found at surgery.

The Use of Molecular Breast Imaging in the Evaluation of Tumor Response to Neoadjuvant Therapy in Women With Breast Cancer

The Use of Molecular Breast Imaging in the Evaluation of Tumor Response to Neoadjuvant Therapy in Women With Breast Cancer - A Pilot Study

Mayo Clinic

M.D.

Menopause

Estrogens, Conjugated (USP)

Medroxyprogesterone Acetate

Medroxyprogesterone

Women receiving HRT treatment of Premarin.

Women receiving combination HRT treatment of Premarin + Provera.

Women receiving combination HRT treatment of Premarin + Prometrium.

Lothar Lilge, PhD

Hormone Replacement Therapy (HRT) is a double edged sword: it can alleviate the effects of menopause for a significant proportion of the female population, however for a smaller proportion, it will induce a significant increase in their short-term and lifetime risk to develop breast cancer (BC). Fewer women are prescribed HRT compared to a decade ago due to concerns pertaining to BC by both physicians and patients. By developing a technology that could identify women at risk for the adverse effects of HRT, during the first few months of its use, physicians may offer HRT to a wider proportion of the female population during menopause. More importantly, as it relates to BC prevention, such a technology will identify women at risk and provide a useful decision making tool regarding their care during the menopausal years.

Hormone Replacement Therapy (HRT) provides many benefits to post-menopausal women, which have been overshadowed by an increase in breast cancer in women following HRT, resulting in a negative HRT cost-benefit ratio. Epidemiological studies show evidence of a direct association between HRT use and breast cancer incidence. This increase in incidence was also reflected in an increase of the mammographic breast density (MBD). Endogenous MBD is a well established risk factor for breast cancer which provides a high odds ratio (OR 4 - 6) towards breast cancer. Increases in MBD have been reported in women who initiate HRT, which is of concern as it potentially indicates a greater adverse effect of HRT on those individuals. In these cases, the majority of the incremental MBD increase manifests itself during the first year of use and decreases in the case of therapy cessation. The ability to detect changes in MBD in women commencing HRT treatment, without the ionizing radiation dose penalty imparted by mammography, thus permitting improved monitoring of MBD changes de to HRT, would certainly impact the debate on the applicability of HRT. Women identified as having increased MBD induced by HRT should discontinue its use or modify the prescription as increases in MBD potentially indicates an adverse ratio; women whose MBD has not been adversely affected by HRT can continue its use and reap the benefits of HRT (e.g. relief of climacteric symptoms, beneficial effects against osteoporosis and coronary heart disease).

Optical Breast Spectroscopy (OBS) is a safe and non-invasive optical technique that provides information on breast tissue composition and physiology state. Comparison of breast tissue status over time will provide information on changes in the MBD and breast cancer risk due to interventions such as HRT. To demonstrate that breast tissue status changes with HRT use, we will exploit existing algorithms correlating OBS with various biological outcomes. A completed study on a cohort of 300 healthy women (age 38 to 72) showed a high correlation between OBS optical parameters and Cumulus derived MBD. An ongoing study, to be completed Q3 2008 with an interim analysis available, suggests that OBS parameters can optically detect differences between the contralateral breasts of women with a unilateral carcinoma or ductal carcinoma in situ (DCIS) and healthy controls. Through these studies, two OBS algorithms ("density" and "risk") are available for application in the proposed study. The algorithms take OBS optical data as input and output OBS-derived percent breast density (PBD) and OBS-derived risk values. The aim of the study is to examine changes in OBS-derived PBD and OBS-derived risk values due to the initiation, use and cessation of HRT over a 1 year period. The case group will comprise a population of post-menopausal women who have elected to undergo a HRT regiment designed to last at least 1 year but had no prior HRT treatment. The comparison group (control) will comprise of post-menopausal women not on HRT and had no prior HRT treatment. OBS measurements will be assessed at intervals corresponding to: baseline (pre-HRT), 1 month, 3 months, 6 months, and 1 year after initiation of HRT use, and 3 months after cessation of treatment (in cases where HRT is discontinued within one year). Blood will be collected at baseline and at 3 months during treatment to examine changes in circulating hormones (estrogen, progesterone). Mammography will be performed at three months during treatment and compared to a screening mammogram (taken within a year prior to HRT treatment) to determine changes in breast density. A Papanicolaou test (or PAP smear) will be performed at baseline to assess endometrial changes. Changes in OBS derived PBD and MBD as well as other pertinent risk values will be examined as a function of time.

Four model groups will be monitored consisting of cases receiving treatments of Premarin, Premarin + Provera combination, or Premarin + Prometrium combination and controls not on HRT. A total of 20 women will be recruited into each group of the four groups. While the total number of women intended for recruitment is small, they are sufficient to enable us to demonstrate that OBS changes as function of MBD changes. Of further interest, we want to determine whether OBS can detect changes prior to changes to MBD in standard clinical setting. In particular, we aim to determine the magnitude of the effect size and the variance within the study groups for later initiation of a larger definitive clinical monitoring trail of HRT effects by OBS.

The long term clinical goal is the identification of women adversely affected by HRT by OBS as they can be advised of alternative methods with possible lower risk to benefit ratio to relieve climacteric symptoms. An overall effect will be a reduction in the population-based incidence of breast cancer while not withholding the beneficial effects of HRT to the majority of women during menopause.

Monitoring of Breast Tissue Change Due to Hormone Replacement Therapy in Post-menopausal Women Using OBS

Short-term Evaluations of Breast Tissue Change in Post-menopausal Women Using Optical Breast Spectroscopy (OBS)

Unity Health Toronto

University Health Network, Toronto

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Letrozole Versus Hormonal Preparation in Frozen Cycles of PCOS Patients.	NCT05168865	Frozen Embryo T... Polycystic Ovar... Letrozole Hormone Replace... Live Birth Miscarriage	Letrozole 2.5mg	20 Years - 40 Years	Dubai Fertility Center
Evaluation of Women With Endocrine and Reproductive-Related Conditions	NCT00001850	Endocrine Disea... Infertility Leiomyoma Endometriosis Fibroids		1 Year - 85 Years	National Institutes of Health Clinical Center (CC)
Women's Health Initiative (WHI)	NCT00000611	Bone Diseases Breast Neoplasm... Cardiovascular ... Colonic Neoplas... Coronary Diseas... Heart Diseases Myocardial Isch... Osteoporosis Postmenopause	hormone replace... estrogens progestins estrogen replac... diet, fat-restr... calcium vitamin D dietary supplem...	50 Years - 79 Years	National Heart, Lung, and Blood Institute (NHLBI)
Danish Osteoporosis Prevention Study	NCT00252408	Osteoporosis	Hormone replace...	45 Years - 58 Years	University of Aarhus
The Use of Molecular Breast Imaging in the Evaluation of Tumor Response to Neoadjuvant Therapy in Women With Breast Cancer	NCT01023802	Neoadjuvant The... Chemotherapy Hormone Replace... Breast Cancer		18 Years -	Mayo Clinic
Women's Health Initiative (WHI)	NCT00000611	Bone Diseases Breast Neoplasm... Cardiovascular ... Colonic Neoplas... Coronary Diseas... Heart Diseases Myocardial Isch... Osteoporosis Postmenopause	hormone replace... estrogens progestins estrogen replac... diet, fat-restr... calcium vitamin D dietary supplem...	50 Years - 79 Years	National Heart, Lung, and Blood Institute (NHLBI)
Monitoring of Breast Tissue Change Due to Hormone Replacement Therapy in Post-menopausal Women Using OBS	NCT00797199	Breast Cancer		30 Years - 65 Years	University Health Network, Toronto

Spots Global Cancer Trial Database for hormone replacement therapy