A lot of women are prescribed progesterone for the treatment of threatened abortion and staining during early pregnancy – with the ostensible purpose of saving the pregnancy. Unfortunately some doctors use progesterone as a kind of insurance against miscarriage and this practice is becoming increasingly common. The progesterone levels in the body are naturally higher during early pregnancy. So several doctors think that adding a bit of exogenous progesterone for support will have little or no adverse effects. However not all adverse events are immediately apparent.
A recent paper by Reinisch et al, in Archives of sexual behaviour had a provocative argument. The intake of synthetic progestin by the mother, called lutocyclin was associated with a higher risk of bisexuality in the child. As sexual behaviour and preference can only be discerned after puberty, this intriguing signal is very interesting. Several animal studies show that exposure to progesterone in the prenatal period can cause weird sexual behaviour in the offspring.However animals are largely free of the societal pressures that humans have to face – so the data cannot be directly extrapolated to humans.
The determinants of human sexuality are fiendishly complex. Many are unknown. It is conceivable that exposure of the developing fetal brain to exogenous hormones can have effects that are very hard to predict. To make matters worse, the long latent period between prenatal exposure and the first sexual behaviour makes it very hard to pin any adverse event on a particular drug / event. People with bad experience tend to remember the details that they feel might be related to the issue – the recall bias. Furtheremore it is impractical and unethical to round up a group of mothers, randomly split them into two groups and given one group progesterone and see what happens to their kids later on.So how can we investigate the possible link , between prenatal progesterone exposure and sexual preference in the child?
One way is to have a natural birth cohort. To identify the women who were given progesterone and track the children from birth and compare them with the children of women who were not given progesterone. As long as the children are of the same social background and have good follow up, we might be able to compare them. That’s what the authors did in the study.
They had tracked 34 individuals and found that the tendency for bisexuality (being attracted to both sexes) is higher in the children of mothers treated with progesterone. There was also a dose response effect – crucial in determining casuality. The Bradford hill criteria are commonly used to assess causality
The children of mothers who were treated with higher doses for longer duration were more likely to have bisexuality. The sexual preferences were self reported. Interestingly heterosexual attraction was not diminished in those who reported bisexuality – it ‘s as if they had developed additional attraction to the same sex as well. This is different from a shift to homosexuality – thus showing that a bidimensional model where in both homo and heterosexuality exists in the same individual, with each one having high and low poles.
What do we make of this research?
As we all know , it takes a lot more than a single study to come to conclusions. However a single study which shows consistent findings, with a dose response effect, should raise some alarm. There are some doubts, whether the trade name lutocyclin ( made in late 1950’s, the time the birth cohort was established) was actually progesterone. However the author seems certain. The magnitude of effect and the numbers are small, but the effect itself appears concerning.
In the mean time, it is vitally important that we acknowledge the uncertainty surrounding the effects of prenatal hormone exposure. Studying the effects of such hormone use is very hard.
Hormones are to be used with care – a lot of things like metabolism, receptor affinity,distribution and post receptor mechanisms can result in varying effects in different individuals.
The most important question to ask before taking a hormone is – do I really need it?