Premenstrual syndrome

Premenstrual syndrome (PMS) is a condition that leads to psychological, physical and behavioural symptoms that occur during the luteal phase of the menstrual cycle:

It is important though that we differentiate between PMS and the physiological menstrual symptoms that the majority of women experience before their menses, which is known as menstrual molimina. These are the physiological symptoms that you notice prior to your menses but do not interfere with the daily routine. PMS is when the symptoms cause significant personal, interpersonal and/or functional impairments during the literal phase.

PMS in its severe form is known as premenstrual dysmorphic disorder (PMDD), which according to DSM-V is when a woman suffers from at least 5 of 11 distinct psychological premenstrual symptoms (one of which must include mood). It also must be severe enough to impair normal daily function.

🏃‍♀️ Physiology

The average menstrual cycle is 28 days but can vary (21-35 days). Day 0 is considered as the first day of menses and day 28 is the last day before the next menses begins.

The menstrual cycle itself includes 2 cycles:

1. Ovarian cycle - this cycle itself can be subdivided into 2 phases:
1. Follicular phase - this occurs in the first 14 days. Gonadotropin releasing hormone (GnRH) from the hypothalamus triggers the release of FSH from the anterior pituitary which subsequently stimulates the development of the ovarian follicles. 1 follicle (sometimes 2) will become dominant while the others will shrink and die. This follicle transitions from a primordial → primary → secondary follicle. As the follicle grows, it secretes increasingly more oestrogen. Oestrogen is responsible for the end of menses (stopping the discharge of blood) and thickening of the endometrium. Positive feedback results In a dramatic oestrogen increase by the pre-ovulatory follicle. This in turn causes a dramatic rise in luteinising hormone (LH) that is known as the LH surge. This surge triggers ovulation and the beginning of the second phase in the ovarian cycle.
2. Luteal phase - the luteal phase is when the oocyte is released from the follicle. The follicle then becomes the corpus luteum which begins to secrete progesterone. Progesterone is responsible for preparing the endometrial lining for implantation. If there is no implantation, the corpus luteum will degenerate into the corpus albicans which does not produce any hormones. This results in a sharp drop in oestrogen and progesterone levels → endometrial shedding and the start of menses. The drop in oestrogen and progesterone removes the negative feedback on GnRH → GnRH levels to increase and stimulate FSH to begin the follicular phase once more.

2. Uterine cycle - itself can be divided into 3 phases:
1. Menstrual phase - menses is initiated every month due to the drop in oestrogen and progesterone and hence nothing is able to maintain the endometrial lining.
2. Proliferative phase - this coincides with the follicular phase of the ovarian cycle. This is when the endometrium is proliferating and thickening due to high oestrogen levels. Oestrogen also alters the pH to make it more alkaline, thus thinning the cervical mucous to allow for sperm to enter.
3. Secretory phase - this coincides with the luteal phase of the ovaries. It reflects the secretions of the ovum which may or may not be fertilised and implanted into the uterus.

Pathophysiology

We are not entirely sure of the causes of PMS, however, we believe that fluctuating levels of oestrogen and progesterone during the luteal phase is reponsivle for PMS and PMDD. It is believed that they play a role in interacting with nuerotransmitters such as serotonin and GABA.

Other theories suggest that there is increased progesterone sensitivity.

🔢 Classification

PMS can be classified into core PMDs and variant PMDs:

• Core PMD - this is the most commonly encountered and widely recognised type of PMS.
• Symptoms must be severe enough to affect daily functioning or interfere with the woman’s work, school, performance or interpersonal relationships.
• Symptoms are nonspecific and recur in ovulatory cycles. They must be present during the luteal phase and resolve as menstruation begins or soon after. It is followed by a symptom-free week.
• There is no limit to the symptoms experienced, but some women will predominantly have psychological symptoms or predominantly physical symptoms, or a mix.
• Variant PMDs - these are PMDs that do not meet the criteria for core PMDs. There are 4 subtypes:
1. Premenstrual exacerbation of underlying disorder - symptoms of an underlying disorder (such as diabetes, depression, epilepsy, asthma, migraine) become significantly worse.
2. Non-ovulatory PMD - symptoms result from ovarian activity rather than ovulation. It is poorly understood.
3. Progestogen-induced PMD -this is when you have symptoms of PMS with exogenous progesterone administration (as in contraceptives and HRT).
4. PMD with absent menstruation - symptoms arise due to continued ovarian activity despite suppression of menstruation (e.g. after hysterectomy or endometrial ablation, or LNG-IUS).

😷 Presentation

There are plenty of symptoms that may be present, and they can be divided into either psychological, physical and behavioural symptoms:

🔍 Investigations

🥇 A good history is necessary. We can make a diagnosis based on a symptom diary for 2 menstrual cycles that describe the onset of symptoms in the luteal phase and resolution after commencing menses.

🏆 A definitive diagnosis can be made by trialling a GnRH agonist for 3 months:

• Buserelin is an example of a GnRH agonist. They cause a surge of oestrogen and progesterone initially, but continued administration desensitises the receptors which subsequently decreases FSH and LH → decrease in oestrogen and progesterone and inhibition of the ovarian cycle. Diagnosis can be confirmed if there is resolution of symptoms after ovarian suppression.

🧰 Management

Management should be tailored to the severity and type of symptoms, preference of the woman, and the desire to conceive:

Mild PMS symptoms:

• Lifestyle advice - regular, frequent, balanced meals which are rich in complex carbohydrates (whole grains, legumes, vegetables).

Moderate PMS symptoms:

• Combined oral contraceptive (COC)
• Yasmin (drospirenone and ethinyloestradiol).

Severe PMS symptoms:

• SSRI
• Fluoxetine
• CBT
• GnRH analogues - these induce a menopausal state. HRT may be combined to mitigate the effects of osteoporosis.

• Danazol - can be used for cyclical breast pain. Tamoxifen may be considered too.
• Spirinolactone - may be used for bloating, water retention and breast swelling.
• Transdermal oestrogen patches & cyclical progestogens or LNG-IUS may be used to improve symptoms in general as well.