Birth Control Pill Could Cause Long-Term Problems With Testosterone

In the January issue of The Journal of Sexual Medicine, researchers have published a new investigation measuring sex hormone binding globulin (SHBG) before and after discontinuation of the oral contraceptive pill. The research concluded that women who used the oral contraceptive pill may be exposed to long-term problems from low values of "unbound" testosterone potentially leading to continuing sexual, metabolic, and mental health consequences.

Sex hormone binding globulin (SHBG) is the protein that binds testosterone, rendering it unavailable for a woman's physiologic needs. The study showed that in women with sexual dysfunction, elevated SHBG in "Oral Contraceptive Discontinued-Users" did not decrease to values consistent with those of "Never-Users of Oral Contraceptive".

Thus, as a consequence of the chronic elevation in sex hormone binding globulin levels, pill users may be at risk for long-standing health problems, including sexual dysfunction. Oral contraceptives have been the preferred method of birth control because of their ease of use and high rate of effectiveness. However, in some women oral contraceptives have ironically been associated with women's sexual health problems and testosterone hormonal problems. Now there are data that oral contraceptive pills may have lasting adverse effects on the hormone testosterone.
The research, in an article entitled: "Impact of Oral Contraceptives on Sex Hormone Binding Globulin and Androgen Levels: A Retrospective Study in Women with Sexual Dysfunction" published in The Journal of Sexual Medicine, involved 124 premenopausal women with sexual health complaints for more than 6 months.

Three groups of women were defined:
i) 62 "Oral Contraceptive Continued-Users" had been on oral contraceptives for more than 6 months and continued taking them,
ii) 39 "Oral Contraceptive Discontinued-Users" had been on oral contraceptives for more than 6 months and discontinued them, and
iii) 23 "Never-Users of Oral Contraceptives" had never taken oral contraceptives. SHBG values were compared at baseline (groups i, ii and iii), while on the oral contraceptive (groups i and ii), and well beyond the 7 day half-life of sex hormone binding globulin at 49-120 (mean 80) days and more than 120 (mean 196) days after discontinuation of oral contraceptives (group ii).

The researchers concluded that SHBG values in the "Oral Contraceptive Continued-Users" were 4 times higher than those in the "Never-Users of Oral Contraceptives". Despite a decrease in SHBG values after discontinuation of oral contraceptive pill use, SHBG levels in "Oral Contraceptive Discontinued-Users" remained elevated when compared to "Never-Users of Oral Contraceptives".

This led to the question of whether prolonged exposure to the synthetic estrogens of oral contraceptives induces gene imprinting and increased gene expression of SHBG in the liver in some women who have used the oral contraceptives. Dr. Claudia Panzer, an endocrinologist in Denver, CO and lead author of the study, noted that "it is important for physicians prescribing oral contraceptives to point out to their patients potential sexual side effects, such as decreased desire, arousal, decreased lubrication and increased sexual pain. Also if women present with these complaints, it is crucial to recognize the link between sexual dysfunction and the oral contraceptive and not to attribute these complaints solely to psychological causes."

"An interesting observation was that the use of oral contraceptives led to changes in the synthesis of SHBG which were not completely reversible in our time frame of observation. This can lead to lower levels of 'unbound' testosterone, which is thought to play a major role in female sexual health. It would be important to conduct long-term studies to see if these increased SHBG changes are permanent," added Dr. Panzer. Dr. Andre Guay, study co-author and Director of the Center for Sexual Function/Endocrinology in Peabody, MA affirmed that this study is a revelation and that the results have been remarkable.

"For years we have known that a subset of women using oral contraceptive agents suffer from decreased sex drive," states Dr. Guay. "We know that the birth control pill suppresses both ovulation and also the male hormones that the ovaries make in larger amounts during the middle third of the menstrual cycle. SHBG binds the testosterone, therefore, these pills decrease a woman's male hormone availability by two separate mechanisms. No wonder so many women have had symptoms."

"This work is the culmination of 7 years of observational research in which we noted in our practice many women with sexual dysfunction who had used the oral contraceptive but whose sexual and hormonal problems persisted despite stopping the birth control pill," said Dr. Irwin Goldstein, a urologist and senior author of the research. "There are approximately 100 million women worldwide who currently use oral contraceptives, so it is obvious that more extensive research investigations are needed.

The oral contraceptive has been around for over 40 years, but no one had previously looked at the long-term effects of SHBG in these women. The larger problem is that there have been limited research efforts in women's sexual health problems in contrast to investigatory efforts in other areas of women's health or even in male sexual dysfunction."

To better appreciate the scope of the problem, oral contraceptives were introduced in the USA in 1960 and are currently used for reversible pharmacologic birth control by over 10 million women in the US, including 80% of all American women born since 1945 and, more specifically, 27% of women ages 15-44 and 53% of women age 20-24 years. By providing a potent synthetic estrogen (ethinyl estradiol) and a potent synthetic progesterone (for example - norethindrone), highly effective contraception is achieved by diminishing the levels of FSH and LH, thereby reducing metabolic activity of the ovary including the suppression of ovulation. Several studies over the last 30 years reported negative effects of oral contraceptives on sexual function, including diminished sexual interest and arousal, suppression of female initiated sexual activity, decreased frequency of sexual intercourse and sexual enjoyment.

Androgens such as testosterone are important modulators of sexual function. Oral contraceptives decrease circulating levels of androgens by direct inhibition of androgen production in the ovaries and by a marked increase in the hepatic synthesis of sex-hormone binding globulin, the major binding protein for gonadal steroids in the circulation. The combination of these two mechanisms leads to low circulating levels of "unbound" or "free" testosterone.
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