Scientists find way to predict timing of menopause

LONDON, June 27 (Reuters) – Iranian scientists say they have developed a way of using a simple blood test to predict accurately when women will reach the menopause, offering the chance for women to plan for family and career far in advance.

The test, which measures levels of a hormone produced by cells in the ovaries, was able to predict the age at which women reached menopause to within an average of 4 months, according to data to be presented at the conference of the European Society of Human Reproduction and Embryology in Rome on Monday.

“The results … could enable us to make a more realistic assessment of women’s reproductive status many years before they reach menopause,” said Ramezani Tehrani of the Shahid Beheshti University of Medical Sciences in Tehran, who led the study.

Experts commenting on the work agreed it was promising, but said its findings would need to be confirmed in larger trials.

“The possibility of an accurate predictor for menopause is very exciting. People have been looking for something like this for years,” said Dagan Wells of the Nuffield Department of Obstetrics and Gynaecology at Oxford University.

The average age for menopause is 51, with ovulation in most women ending sometime between age 40 and 60. But it can happen later or earlier, making it difficult for women who want to develop a career before having babies to know how long to wait.

Tehrani’s team took blood samples from 266 women aged between 20 and 49 who were also taking part in another study called the Tehran Lipid and Glucose Study, which started in 1998.

They then measured concentrations of a hormone called the anti-Mullerian Hormone (AMH) that is produced by cells in women’s ovaries. AMH controls the development of follicles in the ovaries from which eggs develop, and the scientists suspected it might be useful for judging ovarian function.

STATISTICAL MODEL

The researchers took two more blood samples at three yearly intervals and also collected information on the women’s socioeconomic background and reproductive history.

“We developed a statistical model for estimating the age at menopause from a single measurement of AMH concentration,” Tehrani explained in a report on the study. “Using this model, we estimated mean average ages at menopause for women at different time points in their reproductive life span.”

Tehrani said the results showed “a good level of agreement” between predicted and actual age at menopause for the 63 women in the group who reached menopause during the study.

The average difference between the predicted age and the women’s actual age at menopause was a third of a year, and the maximum margin of error was three to four years.

Wells said Tehrani’s team appeared to have hit upon a “fairly accurate algorithm” for predicting menopause.

But said it would be important to see if the method could also help predict the time when fertility effectively ends.

“A woman may cease monthly ovulation and experience menopause at 50, but she will probably have been effectively infertile for several years prior to this,” he said. “It will be important to let patients know that fertility will have declined greatly in the years preceding the final ovulation.”

FDA Lifts Full Clinical Hold on Repros` Proellex®

Company allowed to conduct low dose study to determine whether a safe and
potentially effective dose of Proellex can be developed
THE WOODLANDS, Texas–(Business Wire)–
Repros Therapeutics Inc. (NasdaqCM:RPRX) today announced it has received written
confirmation from the FDA noting the full clinical hold on Proellex® has been
lifted. The Company will be allowed to run a single study under the new partial
clinical hold status. The new low dose study is designed to explore both safety
and signals of efficacy in an escalating dose fashion.

The new study will test 5 different doses of Proellex (1, 3, 6, 9 and 12 mg)
with 1 mg being the first dose tested. Each dose will be compared to placebo
with weekly assessments of liver function during both the placebo and drug
period. Higher doses will not be studied until the Company is confident that it
is safe to proceed to the next dose and has reported the safety findings to the
FDA. Subjects will be dosed with the active drug for 10 weeks, which will allow
for adequate time to determine the impact of a given dose on trends in liver
function. Each dose will be tested in 12 different subjects and assessment of
pharmacokinetic parameters will be obtained at start of dosing and end of the
dosing period to determine overall and maximum drug exposure for a given dose.
The Company will also monitor changes in menstrual bleeding patterns and
ovulation as well as changes in endometrial thickness. The FDA requires that an
independent Drug Safety Monitoring Board be established and that the “Informed
Consent” clearly state the liver toxicity previously experienced with Proellex.
The Company believes the toxicity experienced was dose dependent and that the
lower doses being tested now are outside the range where toxicity was previously
seen.

In a 120 patient study of Proellex as a treatment of uterine fibroids conducted
in the United States (roughly 40 subjects per arm) both a 12.5 and 25 mg dose of
Proellex were compared to placebo. In this study both the 12.5 and 25 mg doses
achieved highly statistically significant results when compared to placebo when
menstrual bleeding was assessed (p< 0.0001). The two doses also achieved highly
statistically significant improvement in quality of life measures using the
Uterine Fibroid Symptom Quality of Life questionnaire developed and validated by
Georgetown University and used in the development of device like treatments of
uterine fibroids such as uterine artery embolization. There was no statistical
difference in efficacy measures between the two doses. Importantly in the Phase
II US trial a significant percentage of women stopped menstruating. Over 80% of
women on both the 12.5 and 25 mg doses exhibited no menses during the three
month trial whereas all women on placebo exhibited at least one menses. The
Company believes that the evaluation of ovulation and menstrual bleeding
patterns in the low dose trial will provide strong evidence for efficacy
warranting further development.

The Company plans to proceed with the manufacture of the lower doses of Proellex
capsules and hopes to begin dosing subjects this summer. Though the new study is
more complex than that originally submitted to the FDA, the Company believes it
can complete the trial within roughly 18 months after first dose. Presuming a
safe and effective dose is identified and the FDA is in agreement, Repros
anticipates that it will be able to proceed with large efficacy trials for both
uterine fibroids and endometriosis, subject to available funds, or outlicense of
the product to a major pharmaceutical company.

Repros is presently sufficiently capitalized to commence the study due to the
proceeds it has generated from the direct sales of shares of common stock into
the capital market from its shelf registration statement, with Ladenburg Thalman
as placement agent. To date the Company has raised over $5.5 million since it
has begun the trading program. No warrants or discounted shares have been
offered or issued as part of this “at the market” financing.

About Repros Therapeutics Inc.

Repros Therapeutics focuses on the development of oral small molecule drugs for
major unmet medical needs that treat male and female reproductive disorders.

Any statements that are not historical facts contained in this release are
forward-looking statements that involve risks and uncertainties, including
Repros’ ability to have the partial hold on Proellex lifted and to determine a
safe and effective dose for Proellex, maintain its listing on the NASDAQ Capital
Market, raise needed additional capital on a timely basis in order for it to
continue to fund its operations and pursue its development activities, and such
other risks which are identified in the Company’s most recent Annual Report on
Form 10-K and in any subsequent quarterly reports on Form 10-Q.These documents
are available on request from Repros Therapeutics or at www.sec.gov.Repros
disclaims any intention or obligation to update or revise any forward-looking
statements, whether as a result of new information, future events or otherwise.

For more information, please visit the Company’s website at

http://www.reprosrx.com.

Repros Therapeutics Inc.
Joseph Podolski, 281-719-3447
President and Chief Executive Officer

Copyright Business Wire 2010

Daily sex ‘helps improve sperm quality’

Washington, July 1 (ANI): Having sex every day improves men’s sperm quality, an Australian study has revealed.

In a study of men with fertility problems, researchers found that daily ejaculation for a week cut the amount of DNA damage seen in sperm samples.

“All that we knew was that intercourse on the day of ovulation offered the highest chance of pregnancy, but we did not know what was the best advice for the period leading up to ovulation or egg retrieval for IVF,” Dr David Greening, an obstetrician and gynaecologist with sub specialist training in reproductive endocrinology and infertility at Sydney IVF, Wollongong, Australia, said.

“I thought that frequent ejaculation might be a physiological mechanism to improve sperm DNA damage, while maintaining semen levels within the normal, fertile range,” he added.

To investigate this hypothesis, Greening studied 118 men who had higher than normal sperm DNA damage as indicated by a DNA Fragmentation Index (DFI).

Men who had a more than 15 percent of their sperm damaged were eligible for the trial. At Sydney IVF, sperm DNA damage is defined as less than 15 percent DFI for excellent quality sperm, 15-24 percent DFI for good, 25-29 percent DFI for fair and more than 29 percent DFI for poor quality; but other laboratories can have slightly different ranges.

The men were instructed to ejaculate daily for seven days, and no other treatment or lifestyle changes were suggested. Before they started, levels of DNA damage ranged between 15 percent and 98 percent DFI, with an average 34 percent DFI when measured after three days’ abstinence.

When the men’s sperm was re-assessed on the seventh day, Greening found that 81 percent men had an average 12 percent decrease in their sperm DNA damage, while 19 percent men and an average increase in damage of nearly 10 percent. The average for the whole group dropped to 26 percent DFI.

“Although the mean average was 26 percent which is in the ‘fair’ range for sperm quality, this included 18 percent of men whose sperm DNA damage increased as well as those whose DNA damage decreased,” Greening said.

“Amongst the men whose damage decreased, their average dropped by 12 percent to just under 23 percent DFI, which puts them in the ‘good’ range.

Also, more men moved into the ‘good’ range and out of the ‘poor’ or ‘fair’ range. These changes were substantial and statistically highly significant.

“In addition, we found that although frequent ejaculation decreased semen volume and sperm concentrations, it did not compromise sperm motility and, in fact, this rose slightly but significantly.

“Further research is required to see whether the improvement in these men’s sperm quality translates into better pregnancy rates, but other, previous studies have shown the relationship between sperm DNA damage and pregnancy rates,” he added.

Greening said he thought the reason why sperm quality improved with frequent ejaculation was because the sperm had a shorter exposure in the testicular ducts and epididymis to reactive oxygen species – very small molecules, high levels of which can damage cells.

“The remainder of the men who had an increase in DFI might have a different explanation for their sperm DNA damage,” he said.

The study has been presented at the 25th annual meeting of the European Society of Human Reproduction and Embryology in Amsterdam. (ANI)

Key proteins linked to ovulation identified

Washington, May 15 (ANI): Researchers from the National Institutes of Health have identified two proteins that play a vital role in ovulation process.

The discovery, researchers hope, would help in treating infertility resulting from a failure of ovulation. It will also aid in developing new means to prevent pregnancy by preventing the release of the egg.

The proteins, called ERK1 and ERK2, appear to bring about the maturation and release of the egg.

“Ovulation results from a complex interplay of chemical sequences,” said Dr Duane Alexander, director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

“The researchers have identified a crucial biochemical intermediary controlling the release of the egg.

“The finding advances our understanding and may one day contribute to new treatments for infertility as well as new ways to prevent pregnancy from occurring,” Alexander added.

ERK1 and ERK2 are a critical nexus between the surge in luteinizing hormone and ovulation, said Dr Louis V. De Paolo chief of the NICHD Reproductive Sciences Branch.

“This is a key chemical pathway that affects not only ovulation, but egg cell maturation and granulosa cell differentiation into luteal cells,” Dr. De Paolo added.

Luteinizing hormone is a hormone produced by the anterior pituitary gland.

Previously, researchers did not know how luteinizing hormone triggered the ovary’s release of the egg and the production of progesterone by the granulosa cells.

In the current study, the researchers discerned that luteinizing hormone appears to signal the release of the ERK 1 and ERK 2 proteins.

“We’re still at the tip of the iceberg. We need to understand it all,” said De Paolo said. (ANI)

Artificial ovary ‘turns immature human egg into mature one’

London, May 08 (ANI): An artificial ovary grown in lab by researchers at the Women and Infants Hospital in Providence, Rhode Island, has been able to turn an immature egg into one that is ready to be fertilised.

Lead researchers Sandra Carson and Stephan Krotz had created the artificial ovary using slivers of ovarian tissue.

For this work, the researchers started with theca cells, which form the outer coating of the follicle that holds the egg and produces a precursor to oestrogen.

They got their cells from ovaries that had been removed from young women for other reasons. A gel mould shaped like a honeycomb was seeded with theca cells, which grew into a structure 2 millimetres wide.

From the fluid surrounding eggs of another set of women undergoing IVF the team extracted granulosa cells, which produce the hormone oestradiol and help eggs to mature.

They used a mould to form them into spherical clumps, which they placed into cavities in the honeycomb.

Next, they took a human egg that was about one week shy of ovulation and placed it into the structure along with follicle-stimulating hormone, which helps egg growth but is not released in the ovaries.

The egg took just 72 hours to develop to the point where it could be fertilised: at this point it had developed a “polar body”, a small structure only produced once an egg is mature.

Scientists say that the next step will be to see if the ovary can mature even younger eggs, known as primordial cells, which women have in their thousands.

“We’re hoping to take eggs that are very immature and mature them,” New Scientist quoted Carson as saying.

Krotz reckons this could be done in 10 days, compared with the 280 or more days it would take in a woman’s body.

Eggs seem to mature faster outside the body, which may be because the artificial ovary lacks factors produced by the body that inhibit the process.

The researchers reported their findings on 2 May at a meeting of the New England Fertility Society in New Hampshire. (ANI)

Why women store fat more efficiently than men

Melbourne, Apr 7 (ANI): Oestrogen, the female sex hormone, reduces a woman’s ability to burn fat after having a meal, say researchers.

The finding, by Sydney endocrinologist Associate Professor Tony O’Sullivan, of the University of NSW and St George Hospital, Sydney, may help explain why ladies store fat more efficiently than men.

The study has been published in the journal, Obesity Reviews.

To reach the conclusion, the researchers pooled together research by himself and others to explain why women have on average 6 to 11percent more body fat than men, despite males generally eating more.

The hypothesis suggests a fat-storing mechanism kicks in during puberty and early pregnancy for biological reasons. During times of scarce food, extra kilograms may mean survival.

Tony said that body fat is also linked to fertility as ovulation can stop if underweight.

“Female puberty and early pregnancy – times of increased oestrogen – could be seen as states of efficient fat storage in preparation for fertility, foetal development and lactation,” ABC Online quoted him, as saying.

“There’s strong preliminary evidence, but further research is needed.

“The hypothesis stems from the fact women have a higher percentage of body fat than men, yet when you look at dietary intake, women don’t eat more fat and calories than men, they normally eat less.

“It suggests when puberty occurs women change the way they metabolise fat, storing more fat from their diet instead of burning it up,” the researcher added.

Research supporting the notion shows that in the first 12 to 15 weeks of pregnancy women put on an average 2 to 3 kilograms of fat despite not eating more or exercising less. (ANI)

‘KISS’ therapy offers new hope for infertile women

Washington, Mar 17 (ANI): British researchers claim that hormone kisspeptin shows promise as a potential new treatment for infertility.

The study, led by Dr Waljit Dhillo from Imperial College London, has shown that giving kisspeptin to women with infertility can activate the release of sex hormones, which control the menstrual cycle.

According to researchers, the study could lead to a new fertility therapy for women with low sex hormone levels.

Kisspeptin is a product of the KISS-1 gene and is a key regulator of reproductive function. Animals and humans lacking kisspeptin function do not go through puberty and remain sexually immature.

Dr Waljit Dhillo and colleagues have already shown that kisspeptin treatment leads to the production of sex hormones in fertile women.

Now, they have extended their research to look at the effects of kisspeptin in women whose periods have stopped due to a hormone imbalance.

In this study, a group of ten women who were not menstruating and infertile, were injected with either kisspeptin or saline.

Blood samples were then taken to measure their levels of luteinising hormone (LH) and follicle stimulating hormone (FSH), two sex hormones essential for ovulation and fertility.

The researchers found that kisspeptin led to a 48-fold increase in LH and 16-fold increase in FSH, when compared to the control treatment.

This is the first study to show that kisspeptin can stimulate sex hormones in women with infertility and presents kisspeptin as a potential new therapy for human infertility.

Dhillo said: This is a very exciting result and suggests that kisspeptin treatment could restore reproductive function in women with low sex hormone levels. Our future research will focus on determining the best protocol for repeated kisspeptin administration with the hope of developing a new therapy for infertility.”

The research is being presented at the annual Society for Endocrinology BES meeting in Harrogate. (ANI)

Men get turned on most by women in red

Melbourne, Feb 18 (ANI): Going out for a date tonight, but don’t know how to make your partner fall in love with you instinctively? Well, then remember three things: red roses, red lipstick and a red dress.

That’s the suggestion given by US researchers who have found the first scientific examination of why the colour red is often linked to romance.

In the Journal of Personality and Social Psychology study, two University of Rochester, New York, psychologists put the colour to the test by showing men a series of photographs of women where only the colour of the frame, or their clothing, was altered, reports the Courier Mail.

Professor Andrew Elliot and PhD student Daniela Niesta examined the men’s degree of sexual attraction by asking them the question: “Imagine that you are going on a date with this person and have 100 dollars in your wallet. How much would you be willing to spend on your date?”

The researchers attribute the colour’s power to boost sexual attraction to primitive desires.

Researchers also said the rumps of certain female primates like chimpanzees turn red during ovulation due to increased blood flow, making males more attracted to these females. (ANI)