This study will evaluate the effects of hormone replacement therapy on patients with Turner syndrome (TS)-a genetic disorder in females in which part or all of one X chromosome is missing. Most girls and women with TS have underdeveloped ovaries-the female reproductive organs that produce the female sex hormones estrogen and progesterone, and smaller amounts of the male sex hormone, testosterone. These hormones affect muscle and bone strength, sex drive, energy, and an overall sense of well being. Estrogen may also play a role in memory and mood and have a protective effect against heart disease. Women with TS have a much higher risk of developing osteoporosis (loss of bone density), high blood pressure, high cholesterol and diabetes than women without this disorder.
Girls and women with Turner syndrome between the ages of 14 and 50 years may be eligible for this 2-year study. Three months before beginning treatment, all patients will wear an estrogen patch and take a progesterone tablet daily for 10 days each month. They will then be randomly assigned to one of two treatment groups to compare the effects of estrogen alone with estrogen plus testosterone on bone strength, muscle and fat mass and psychosocial well being. Both groups will wear an estrogen patch and take oral progesterone. One group will also wear a testosterone patch while the other group will wear a placebo patch (a patch that does not contain any testosterone). Neither study participants nor the doctors will know who is getting the testosterone until the study is complete. Patients will undergo the following procedures before beginning treatment and at 6, 12 and 24 months after starting treatment:
Physical examination.
DEXA scans (dual energy X-ray absorptiometry) to measure body composition and bone thickness. Low radiation X-rays scan the whole body to measure fat, muscle and bone mineral content..
Magnetic resonance imaging (MRI) scan of the abdomen to measure the amount of fat around the internal organs. The patient lies on a stretcher in a large tube surrounded by a magnetic field during the scanning. The procedure uses a strong magnet and radio waves to produce the images.
Heel ultrasound to measure bone thickness. The heel is placed in a chamber and sound waves pass through it to produce images.
Oral glucose tolerance test (OGTT) for diabetes and problems with carbohydrate metabolism. The patient drinks a sugary substance. A small amount of blood is drawn before taking the drink and four times afterwards.
Blood and urine tests to measure blood counts, liver and kidney function, ovarian hormones, growth factors, thyroid function, blood lipids, bone strength markers, and to test for pregnancy.
Blood pressure measurements.
Psychological testing for the effect of treatment on mood, self-esteem, quality of life, social shyness, anxiety and sexual function.
Neurocognitive tests (at first inpatient visit and 1 and 2 years after starting treatment) to measure nonverbal memory and visual-perceptual abilities.
During the hospital admissions, patients will be given a "metabolic diet" that contains specific amounts of salt and carbohydrates to ensure accurate blood pressure and sugar metabolism measurements. Patients will keep a record of their menstrual periods and physical activity throughout the treatment period.

Start Date01 Mar 2001

Sponsor / Collaborator

National Institute of Child Health & Human Development

NCT00001951 / CompletedPhase 2IIT

Hormone Replacement in Young Women With Premature Ovarian Failure

The human ovary produces male sex hormones (androgen) and female sex hormones (estrogen). Currently, androgen is not included in hormone replacement therapy for women with premature ovarian failure. Present hormone replacement therapy (HRT) was designed to treat women who experience ovarian failure at menopause (around the age of 50). However, 1% of women will experience premature failure of the ovaries before the age of 40. There have been no studies conducted to determine proper hormone replacement therapies for these younger women. Some research suggests that the usual menopausal hormone replacement therapy is not adequate to protect young women with premature ovarian failure from developing osteoporosis. Women with premature ovarian failure have abnormally low levels of androgens circulating in their blood. This may contribute to the increase risk for osteoporosis.
This study will compare two treatment plans for women with premature ovarian failure. Treatment plan one will be physiological estrogen hormone replacement. Treatment plan two will be physiological estrogen hormone replacement plus androgen. The study will attempt to determine which plan is more beneficial to women in relation to osteoporosis and heart disease.
The hormones will be contained in patches and given by placing the patches against the patient's skin. The patches were designed to deliver the same amount of hormone as would be normally produced by the ovary in young women.
The success of the treatment will be measured by periodically checking the density of patient's bone in the leg (femoral neck bone) . Researchers will take an initial (baseline) measurement of bone density before beginning treatment and then once a year, for 3 additional years, during treatment. The study will also consider bone density of the spine, bone turnover, heart disease risk factors, and psychological state.

Start Date01 Dec 1999

Sponsor / Collaborator

National Institute of Child Health & Human Development

100 Clinical Results associated with TMTDS

100 Translational Medicine associated with TMTDS

100 Patents (Medical) associated with TMTDS

Literatures (Medical) associated with TMTDS

01 Jul 2000·The Journal of clinical endocrinology and metabolism

Pharmacokinetics of a Novel Testosterone Matrix Transdermal System in Healthy, Premenopausal Women and Women Infected with the Human Immunodeficiency Virus¹

Article

Author: Shen, R ; Beall, G ; Sinha-Hikim, I ; Mazer, N A ; Singh, A B ; Javanbakht, M ; Bhasin, S

The clinical consequences of androgen deficiency in human immunodeficiency virus (HIV)-infected women remain underappreciated. The pharmacokinetics of transdermally administered testosterone in premenopausal women and HIV-infected women have not been studied. In this study we compared the pharmacokinetics of a novel testosterone matrix transdermal system (TMTDS) in healthy premenopausal women and women infected with HIV. Eight menstruating HIV-infected women, 18-50 yr of age, who had been receiving stable antiretroviral therapy, including a protease inhibitor, for at least 12 weeks and nine healthy, menstruating women of comparable age were enrolled. After baseline sampling during a 24-h control period in the early follicular phase (days 1-6), two TMTDS patches were applied with an expected delivery rate of 300 microg testosterone daily over an application period of 3-4 days. After 72 h, the patches were removed, a second set of two patches was applied, and blood samples were drawn over 96 h. Baseline serum total and free testosterone levels were lower in HIV-infected women than in healthy women. A diurnal rhythm of testosterone secretion, with higher levels in the morning and lower levels in the late afternoon, was apparent in both groups of women. Free testosterone levels were in the midnormal range at baseline in healthy women and increased above the upper limit of normal during TMTDS application. In HIV-infected women, free testosterone levels were in the low normal range at baseline and rose into the upper normal range during patch application. Serum total testosterone levels increased into the midnormal range in HIV-infected women and into the upper normal range in healthy women during patch application. The mean increments in free and total testosterone levels were significantly lower in HIV-infected women than in healthy women. Testosterone bioavailability, expressed as the mean +/- SEM baseline-subtracted area under the total testosterone curve, was significantly greater in healthy women than in HIV-infected women [3323 +/- 566 ng/dL x h (115 +/- 20 nmol/L x h) vs. 1506 +/- 316 ng/dL x h (52 +/- 11 nmol/ L x h); P = 0.016]. Assuming a daily testosterone delivery rate of 300 microg/day, the apparent plasma clearance was significantly higher in HIV-infected women than in healthy women (2531 +/- 469 vs. 1127 +/- 217 L/day1 P = 0.022), respectively. There was no significant change from baseline in serum LH, sex hormone-binding globulin, and estradiol levels in either group. Serum FSH levels showed a greater decrease from baseline in healthy women. A regimen of two testosterone patches applied twice a week can maintain serum total and free testosterone levels in the mid- to upper normal range, respectively, in HIV-infected women with low testosterone levels. During TMTDS application, the increments in serum total and free testosterone levels are lower in HIV-infected women than in healthy women, presumably due to increased plasma clearance or decreased absorption. Further studies are needed to assess the effects of physiological androgen replacement in HIV-infected women.

01 Jul 2000·The Journal of clinical endocrinology and metabolismQ2 · MEDICINE

Pharmacokinetics of a Novel Testosterone Matrix Transdermal System in Healthy, Premenopausal Women and Women Infected with the Human Immunodeficiency Virus

Q2 · MEDICINE

Author: Shen, Ruoquen ; Mazer, Norman A. ; Sinha-Hikim, Indrani ; Javanbakht, Marjan ; Bhasin, Shalender ; Singh, Atam B. ; Beall, Gildon

The clin. consequences of androgen deficiency in human immunodeficiency virus (HIV)-infected women remain underappreciated.The pharmacokinetics of transdermally administered testosterone in premenopausal women and HIV-infected women have not been studied.In this study we compared the pharmacokinetics of a novel testosterone matrix transdermal system (TMTDS) in healthy premenopausal women and women infected with HIV.Eight menstruating HIV-infected women, 18-50 yr of age, who had been receiving stable antiretroviral therapy, including a protease inhibitor, for at least 12 wk and nine healthy, menstruating women of comparable age were enrolled.After baseline sampling during a 24-h control period in the early follicular phase (days 1-6), two TMTDS patches were applied with an expected delivery rate of 300 μg testosterone daily over an application period of 3-4 days.After 72 h, the patches were removed, a second set of two patches was applied, and blood samples were drawn over 96 h.Baseline serum total and free testosterone levels were lower in HIV-infected women than in healthy women.A diurnal rhythm of testosterone secretion, with higher levels in the morning and lower levels in the late afternoon, was apparent in both groups of women.Free testosterone levels were in the mid-normal range at baseline in healthy women and increased above the upper limit of normal during TMTDS application.In HIV-infected women, free testosterone levels were in the low normal range at baseline and rose into the upper normal range during patch application.Serum total testosterone levels increased into the midnormal range in HIV-infected women and into the upper normal range in healthy women during patch application.The mean increments in free and total testosterone levels were significantly lower in HIV-infected women than in healthy women.Testosterone bioavailability, expressed as the mean ± SEM baseline-subtracted area under the total testosterone curve, was significantly greater in healthy women than in HIV-infected women [3323 ± 566 ng/dL·h (115 ± 20 nmol/L·h) vs. 1506 ± 316 ng/dL·h (52 ± 11 nmol/L·h); P = 0.016].Assuming a daily testosterone delivery rate of 300 μg/day, the apparent plasma clearance was significantly higher in HIV-infected women than in healthy women (2531 ± 469 vs. 1127 ± 217 L/dayl P = 0.022), resp.There was no significant change from baseline in serum LH, sex hormone-binding globulin, and estradiol levels in either group.Serum FSH levels showed a greater decrease from baseline in healthy women.A regimen of two testosterone patches applied twice a week can maintain serum total and free testosterone levels in the mid- to upper normal range, resp., in HIV-infected women with low testosterone levels.During TMTDS application, the increments in serum total and free testosterone levels are lower in HIV-infected women than in healthy women, presumably due to increased plasma clearance or decreased absorption.Further studies are needed to assess the effects of physiol. androgen replacement in HIV-infected women.

01 Mar 2000·Journal of controlled release : official journal of the Controlled Release SocietyQ1 · MEDICINE

New clinical applications of transdermal testosterone delivery in men and women

Q1 · MEDICINE

Article

Author: Mazer, N A

This paper reviews recent progress in the development and clinical application of testosterone transdermal delivery systems designed for physiological replacement therapy in men and women. The biopharmaceutic goal of physiologic replacement therapy is to produce serum levels and circadian patterns of testosterone and its active metabolites that mimic the normal physiology of testosterone in the particular target population. For the treatment of adult hypogonadal men, the nightly 24 h application of the Androderm testosterone transdermal system (5 mg per day) achieves this goal - as demonstrated in a series of clinical pharmacokinetic studies. For the treatment of adolescent males, physiologic replacement can be approximated by modifying the dose and duration of Androderm application so as to mimic the patterns of nocturnal testosterone secretion observed during puberty. With the objective of providing physiological replacement for women with diminished testosterone production, an experimental testosterone matrix transdermal system (TMTDS) has been developed and is currently undergoing clinical evaluation. In parallel with the development of testosterone transdermal systems, physicians have been investigating a number of conditions, in both males and females, where testosterone production is diminished and replacement therapy may be beneficial. Three of these new clinical applications will be illustrated - the use of Androderm for the treatment of adolescent males with beta-thalassemia, the use of Androderm for the treatment of HIV+ men, and the use of the TMTDS for the treatment of HIV+ women. From the biopharmaceutic and clinical perspectives, the development of testosterone transdermal systems represents an important achievement in controlled drug delivery.

100 Deals associated with TMTDS

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Anxiety	Phase 2	US	National Institute of Child Health & Human Development	31 Mar 2001
Diabetes Mellitus, Type 2	Phase 2	US	National Institute of Child Health & Human Development	31 Mar 2001
Dwarfism	Phase 2	US	National Institute of Child Health & Human Development	31 Mar 2001
Dyslipidemias	Phase 2	US	National Institute of Child Health & Human Development	31 Mar 2001
Gonadal Dysgenesis, 46,XX	Phase 2	US	National Institute of Child Health & Human Development	31 Mar 2001
Hypertension	Phase 2	US	National Institute of Child Health & Human Development	31 Mar 2001
Insulin Resistance	Phase 2	US	National Institute of Child Health & Human Development	31 Mar 2001
Timothy Syndrome	Phase 2	US	National Institute of Child Health & Human Development	31 Mar 2001
Osteoporosis	Phase 2	US	National Institute of Child Health & Human Development	21 Mar 2001
Turner Syndrome	Phase 2	US	National Institute of Child Health & Human Development	21 Mar 2001

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Leverages most recent intelligence information, enabling fullest potential.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

TMTDS

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation