Keywords

This chapter aims to provide an overview of the sexual side effects of the medication used in midwifery and obstetrics. Side effects that frequently tend to be forgotten.

The chapter will also provide practical advice to the midwife to discuss the possible sexual side effects and deal with those effects.

1 How Pregnancy Affects the Effects of Medication

Pregnant women are excluded from clinical drug trials, mainly because of the risk of harm to the unborn child. As a result, knowledge about the effectiveness and safety of medication during pregnancy is limited.

During pregnancy, but preferably already when the woman or couple desires a pregnancy, it is necessary to compare the risk of aggravation or recurrence of a medical condition for the unborn against the risks of prescribing medication during pregnancy.

1.1 A Few Words on Pharmacokinetics and Pharmacodynamics

Some knowledge of pharmacokinetics or pharmacodynamics helps understand the side effects of medication. Although they seem complex and abstract processes, PK and PD can be explained quite easily.

Pharmacokinetics (PK) is about the journey of a medicine through the body, from intake to excretion. After all, if a drug does not reach its target organ or tissue, it will not be effective.

A drug first enters the body, usually through the mouth and gastrointestinal tract or the anus. Furthermore, a drug may enter the body through the lungs, skin, vaginal mucosa, or an intravenous, intramuscular, or subcutaneous injection.

After that, the drug is absorbed into the blood circulation, thereby passing to the liver. Certain enzymes in the liver make drugs more water-soluble (hydrophilic) in order to excrete them via the urine or the faeces. This process is called metabolism.

The drug then is distributed throughout the body. It depends on the characteristics of the drug whether it prefers to spread in a ‘watery’ environment (the plasma and muscles; i.e. hydrophilic) or in a ‘fatty’ environment (tissue fat, bone marrow, and brain tissue; i.e. lipophilic). Also, if drugs are bound to proteins in the plasma, they are not capable of leaving the plasma.

Some of these processes change during pregnancy, as we will explain in the next paragraph.

Pharmacodynamics (PD) is about the drug’s effect on the body. So, on the one hand, PD is about the therapeutic effect or the effectiveness of the drug. On the other hand, it concerns the unwanted effects or side effects. The effectiveness and side effects are inextricably linked, as most side effects result from the drug’s pharmacological effect.

For a drug to have an effect, it must reach a target, mostly a receptor, through which a cascade of consequences leads to the therapeutic effect. However, drugs do not ‘know’ where to go. The drug merely spreads through the body based on blood circulation and its preference for watery or fatty tissue. As a result, the drug also reaches and triggers receptors in other organs. That is, in short, the mechanism by which side effects occur: the drug affects other receptors than just the target receptor. Consequently, sexual side effects might develop regardless of the medication used.

1.2 The Changes in PK and PD During Pregnancy

As midwives are most aware, pregnancy is associated with profound changes in the anatomy and physiology of the body, which affects PK and PD. For example, cardiac output increases in pregnancy. As a result, the blood flow through the liver, kidneys, and lungs increases. Consequently, the time decreases in which medication is metabolised and eliminated.

In addition, the blood plasma volume, the total amount of the ‘watery environment’, and the ‘fatty environment’ increase. Hence, hydrophilic drugs will have a lower plasma concentration. Besides, eliminating lipophilic drugs takes more time because they reside in an increased volume of fatty tissue and not in the blood plasma.

The binding of drugs to plasma proteins decreases during pregnancy, which means that a higher amount of the drug can bind to the target and affect whether therapeutic or unwanted.

The activity of the enzymes in the liver that metabolise several drugs change during pregnancy. Some enzymes become more active, while the activity of other enzymes decreases.

In the postpartum period, there is a substantial decrease in sex hormone levels, decreased plasma volume, and normalisation of liver enzyme activity and glomerular filtration rate (GFR, renal clearance).

All these PK changes affect the PD. On the one hand, a higher portion of the drug is free to reach the target. On the other hand, the drug might be eliminated faster than before pregnancy. The drug might also be metabolised quicker or slower than before pregnancy.

In conclusion, PK and PD change significantly during pregnancy. However, what it means in daily practice is hardly investigated. Therefore, the midwife’s watchful eye is of crucial importance.

1.3 What It Means in Daily Practice

In daily practice, there is a clear distinction. Some medication was already taken before pregnancy or will be taken throughout and after pregnancy. On the other hand, there is medication taken only during pregnancy.

A woman who took a specific dosage of medicine before pregnancy might have to change the dosage during pregnancy. Dosage adjustment of medication continued after parturition is also paramount to avoid toxicity or ineffectiveness, depending on whether the woman used a higher or a lower dose during pregnancy. Examples of medication that need dosage adjustments during pregnancy are L-thyroxine, antiepileptic drugs and lithium, most frequently monitored by the prescribing medical specialist.

Dosage instructions are mostly described in the manuals for HCPs. Otherwise, one can consult the summary of the drug’s product characteristics (SmPC). This SmPC can be found in the national registers of approved medication or on the European Medicines Agency (EMA) website. An overview of European registers can be found here.Footnote 1 The register of the EMA can be found here.Footnote 2

  • Please be aware that the general dosage recommendations, as stated in the SmPC or the manuals, might be either too low for a pregnant woman, or too high.

2 How Medication Affects Sexuality

As you can read in almost every chapter in this book, sexual responsiveness results from a complex interplay of biological, psychological, and social factors. This also means that sexual side effects of medication, which are in essence biological, can lead to secondary psychological and even social/relational issues.Footnote 3 Subsequently, these secondary issues may cause a deterioration of the sexual side effects or a continuation of sexual problems after the medication has been stopped.

On the other hand, some medication may also improve sexual function, as shown in Table 19.1.

Table 19.1 Potential sexual effects of medication prescribed before, during or after pregnancy
Full size table

This book will focus on sexual side effects during pregnancy, childbirth and postpartum. In general, sexual issues that women most frequently report are alterations in sexual desire and arousability, in the amount of lubrication (with low lubrication potentially resulting in pain during or after penetration), and altered orgasm capacity.Footnote 4

3 Medication in Detail

Pregnant women are, as said before, excluded from clinical medication trials. Therefore, the knowledge of side effects in pregnant women is scarce. Sexual side effects are not very well studied either. Furthermore, most medication prescribed during pregnancy is given for a short period. As a result, it was a complex task to provide an overview of sexual side effects associated with medication prescribed during pregnancy. Nonetheless, the list in Table 19.1 can be used as a guide.

The list intends to be as complete as possible for the safety and well-being of the woman. Hence, our purpose is neither to encourage nor to discourage prescribing the mentioned medication. Besides, we do not give judgement on the need for the medication or possible alternative therapies.

The list contains generic names since brand names differ per country. Only possible sexual side effects are mentioned. For the purpose of this book, we do not include teratogenic side effects.

4 How to Deal with Suspected Sexual Side Effects

4.1 When to Suspect a Sexual Side Effect

Determining whether an undesired symptom is an adverse drug reaction (ADR) is difficult. The reported symptom could be caused by the medication, by the underlying indication for which the drug has been prescribed, or by other factors which might be unrelated. In the case of sexual symptoms, psychological or social factors may play a role or even be the causal factor of a sexual undesired symptom.

An Illustrative Case

A 38-year old married woman receives antidepressant medication for a depressive disorder. After 2 months, she reports a slight improvement in her depressive symptoms. As side effects, she states that her weight has increased from 63 to 68 kg and that she cannot reach orgasm during sex with her husband. This is new to her.

Although lack of orgasm is a well-known side effect of antidepressants, other factors should be considered. First, the underlying disease could play a role, as depression is most frequently associated with declining sexual satisfaction. Second, the weight increase might result in lower self-esteem in the woman or a decline in her husband’s sexual appetite. Both might lead to a reduction in sexual satisfaction. Third, the partner might be over-focused on his wife having orgasms, resulting in pressure on the woman.

In daily practice, establishing a causal relationship is merely based on clinical judgement. However, this assessment depends on the knowledge and experience of the HCP. To overcome this issue, several causality assessment tools have been developed. A systematic and validated method for the appraisal of the probability of an ADR is the Naranjo score. Answering ten questions leads to a probability score of an ADR. However, the Naranjo score is more time-consuming than the World Health Organization-Uppsala Monitoring Center (WHO-UMC) criteria [31]. Therefore, the latter is shown in Table 19.2. The WHO-UMC has written a comprehensible text on using the criteria, which can be found via this link.

Table 19.2 WHO-UMC causality categories (https://www.who.int/medicines/areas/quality_safety/safety_efficacy/WHOcausality_assessment.pdf)
Full size table

4.2 How to Inquire After Sexual Side Effects?

General reccommendations with regard to talking about sex are discussed in other chapters. Therefore, this paragraph will focus only on the inquiry into the sexual side effects of medication.

Consider talking about side effects in general and sexual side effects as your responsibility since you are a medical professional who will talk about sexuality and sexual side effects more frequently than the woman sitting in your office. Naturally, it might not be easy, but gradually you will become more comfortable.

Before starting, it might help to tell the patient that many people, both patients and HCPs, find sexuality a bit difficult topic to talk openly about, but you consider it too important to avoid the subject. Then you ask for permission or make a general statement. Here are some examples the authors frequently use:

‘Many people using antidepressants experience sexual difficulties. Does that also apply to you?’

‘Many people with these medications have an increase or a decrease in sex drive. Others experience no difference. May I ask how it applies to you?’

‘Sexual complaints are often reported with this medication. Do you mind if we talk about that?’

‘Some people report an improvement in their sexual functioning; others a deterioration. Since starting your medication, have you noticed a change in your sexual functioning?’

After receiving an answer, consider it your duty to inquire as detailed as necessary to understand the exact problem. In addition, consider other factors in order to assess a causal relation with the medication. Next, explain your thoughts or conclusions. Do that also when you do not know what to do. Most women will feel relieved having talked about their concerns.Footnote 5

4.3 How to Manage Sexual Side Effects

Most side effects are not severe and only need explanation. This holds for sexual side effects as well, and even more for medication prescribed during a short period.

When the woman is suffering from sexual side effects, and an explanation is insufficient, dose reduction might be an option. Since dose reduction usually implies a reduction in the therapeutic effect, it is important to consider whether the woman needs the therapeutic effect for her own well-being or for her unborn child.

Another Illustrative Case

A pregnant woman had epilepsy, including grand mal seizures. That is successfully treated with levetiracetam (an antiepileptic drug). The patient reports a decline in desire, arousal, lubrication and orgasm since the start of the medication. She wishes to switch the medication or lower the dose because she suffers from stress due to the side effects.

In this case, one should consider the following strategy. First, although levetiracetam may improve sexual function, patients may experience a decline [32]. Second, the woman experiences stress due to the sexual side effects. This stress will have a certain influence on the unborn child. Third, dose reduction increases the risk of a return of the seizures, which can be supposed to be a more significant threat to the woman and her unborn child. Therefore, a dose reduction or cessation of the antiepileptic medication might be considered inappropriate.

Again, it is important to state that even if dose reduction or cessation of the medication is appropriate, the sexual problems might continue. In that case, the causal relation with the medication might be questioned, or the problems might have evolved into secondary psychological or relational issues.

Most of the time, the cessation of medication due to sexual side effects will not be very common in midwifery since the medication will only be given during a (very) short period. In any case, always follow the tapering (i.e. dose reduction) and cessation advice of the medication guidelines.

When prescribing medication, the midwife has to inform the pregnant woman of possible side effects. This chapter provided support for adequate information about sexual side effects.

5 Conclusion

In conclusion, the medication used before and during pregnancy and in the perinatal period may affect sexuality. The role of the midwife in discussing sexual side effects is most valuable, given their role as a ‘spider’ in the medical ‘web’ of the pregnant woman. Even if a midwife does not have prescribing rights, inquiring after sexual side effects is essential. With the knowledge provided in this chapter, the midwife can undertake a judgement of the causality of sexual changes. And when sexual side effects are present, referral to the prescribing physician is recommended. And of course, referral to a sexologist is also preferable, especially if psychological or social (relationship) factors play a role.