Estradiol May Protect Against Sexually Transmitted Infections

17β-estradiol, more commonly known as estradiol, is an estrogen and the primary female steroid hormone. Estradiol is produced by the follicles within the female ovaries and plays important roles in female menstrual and reproductive cycles. Recent evidence has come to light which has established a protective role of estradiol, more specifically estradiol 2 (E2), in females for the prevention of sexually transmitted infections (STIs). 

The study was carried out under the supervision of Charu Kaushic, professor of Pathology and Molecular Medicine, a member of the Michael G. DeGroote Institute for Infectious Disease Research and McMaster Immunology Research Centre and the lead researcher of this study. The results of the study were subsequently published in PLOS Pathogens.

During the course of the study, experiments were carried out on female mice with Herpes Simplex type 2 (HSV-2) infection. The investigators imbedded estradiol-containing pellets into the female mice. The ovaries of these mice had been removed. This was followed by injection of two phases of HSV-2 vaccine after which the strains of herpes Simplex type 2 (HSV-S) were introduced in these mice. 

Herpes simplex is one of the diseases that are transmitted via sexual contact. The disease affects millions of women around the globe annually. The study has identified the precise mechanism by which estradiol plays a protective role against STIs in females. 

Estradiol: The Protector against STIs

The researchers noted that most of the mice that were injected with the vaccine and the virus survived. The symptoms of herpes simplex were less in these mice in contrast to the mice that were not given the vaccine. 

The researchers looked further to explore the underlying molecular mechanisms. They discovered that estradiol stimulates the dendritic cells present in the vagina to enhance the CD4+ T cell immunity against the invading virus. These responses were mediated via an interleukin 1 (IL-1) dependent pathway. 

The investigators observed an unusual anti-viral activity of the T cells in the cell cultures obtained from the vaginal tract, that was limited to the cells lining the vagina tract and none of the mucosal surfaces present elsewhere in the body showed this activity. 

According to Kaushic, the lead researcher involved in the study, this study is the first of its kind to discover the exact process by which estradiol fortifies the immune system of the body and wards off the sexually transmitted infections. 

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The Future Prospects

This study has effectively established that female sex hormone estradiol can have a major impact on the susceptibility and immune responses towards the sexually transmitted infections. 

The study is expected to have far-reaching implications in terms of development of better preventive strategies for sexually transmitted infections in the form of oral contraceptives. These contraceptives can be administered to women who are at exceptionally high risk of contracting sexually transmitted infections like HIV and HSV, especially in the Sub-Saharan Africa. 

It is also likely that these findings will be used to find out which form of immunity plays a better role in protecting women against the sexually transmitted infections so that better vaccines can be developed to fight STIs. 

Early Estradiol-Based Hormone Therapy Reduces CHD-Related Mortality 

In one the recent studies, researchers have discovered that women who start taking the Estradiol-Based Hormone Therapy (HT) before the age of sixty face lesser risk of mortality associated with the coronary heart disease (CHD). 

Coronary heart disease (CHD) is one of the leading causes of mortality in postmenopausal women. Reduction in the level of estrogen, the female hormone that has a protective role on the female heart, is the main reason underlying this high mortality rate. It has now been established that younger the age at which estradiol HT is started, lesser is the mortality resulting from CHD. 

The study was carried out by Tomi S. Mikkola, MD, PhD, of the department of obstetrics and gynecology at Helsinki University Hospital in Finland and fellow researchers. The basic aim of the study was to look into the “window of opportunity hypothesis” which stipulates that when estrogen only or combined estrogen and progestin hormone therapy is administered to women before the age of 60 years, it protects the heart whereas if it administered after the age of 60, it adds to the mortality rate. 

During the course of the study, the researchers collected data from the national registry of 498,105 women who were taking hormone therapy containing estradiol alone or in combination with progestin. The study lasted from 1994 to 2009 and during this period, the relationship between the time of starting estradiol hormone therapy and CHD related mortality was closely studied. The researchers also looked into the role of progestins. 

Follow-up studies were done on the study subjects either till their death or till the end of the year 2009. Standardized mortality ratios (SMRs) were employed in order to assess the risk of CHD related mortality in women taking HT as compared to the age-matched population. 

Younger Age at the Start of HT Reduces Cardiac Death Risk  

The researchers found that the risk of death from CHD decreased significantly when HT was started before the age of 60 as compared to its initiation after the age of 60. These risks were studied for estradiol only, estradiol with norethisterone acetate and estradiol with tibolone based hormonal therapies for an exposure period of less than five years. 

It was found that no major differences existed between the CHD-related mortality resulting from estradiol with norethisterone acetatehormone therapy and the estradiol with Medroxyprogesterone acetate-based hormone therapy when exposed between 3 and 5 years. 

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The findings of the study have been found to support the “window period” of premenopause since atherosclerosis (thickening of the walls of the blood vessels due to deposition of cholesterol) starts setting in during this time period in women. 

During a sub-analysis carried out on 310,305 women, it was determined that the lesser the age at the start of hormone therapy, the lesser was the risk of mortality resulting from CHD. The addition of various progestins like Medroxyprogesterone acetate, norethisterone acetate or dydrogesterone etc. to the hormonal therapy regime, had no major impact on the CHD related mortality in these women.