Menopause is the state in a woman’s life when menstruation comes to an end permanently due to the loss of ovarian follicular activity. It is clinically diagnosed after 12 months of amenorrhoea. All women who live long enough will go through menopause and it is a normal physiological change that occurs in the life of a woman.
The mean age of menopause in the UK is 51 years old but this is variable depending on many aspects.
Let’s clarify some definitions firstly:
- Pre-menopause - this is the entire reproductive period prior to menopause.
- Peri-menopause - this is the the period in which the first clinical, biological and endocrinological features of menopause begin to appear, such as vasomotor symptoms and irregular menstrual cycles. It ends at 12 months after the last menstrual period, as perimenopause then changes to menopause.
- Post-menopause - this is the period after menopause occurs (i.e. the period one year after the last menstrual period).
- Premature menopause - this is when menopause occurs before the age of 40 years as a result of premature ovarian insufficiency (we will discuss this at the end).
- Early menopause - this is when the ovaries stop functioning between the ages of 40-45 (without any other causes of secondary amenorrhoea).
Pathophysiology
Women are born with a finite number of oocytes, ranging from 1-2 million generally. At pubertal ages there are around 300,000-500,000 oocytes left. This number continues to decline until there are no more left (this is menopause).
An egg takes approximately 14 days mature. This maturation period can be divided into 2 phases. In the initial period, as many as 1000 eggs begin to develop and mature. This occurs independently of gonadal hormone stimulation. The second phase of development requires gonadal hormone stimulation to further stimulate the development of the oocyte.
In pre-pubertal stages there is no gonadal hormone present and so this second stage of development does not take place. As such, these eggs only undergo the first phase of development before withering away without a single one maturing.
During/after puberty, those 1000 eggs or so undergo first phase of development before being stimulated by gonadal hormone which allows a single egg to mature and be ovulated.
Around the age of 37, around 25,000 oocytes remain only. At the age of 52, less than 1000 eggs remain if any at all.
The ovarian follicle/Graafian follicle is responsible for the release of oestrogen initially. After ovulation the corpus luteum releases progesterone as well. This means as we approach menopause, when the follicular activity declines, so does the levels of oestrogen and progesterone. A lack of oestrogen means that the endometrium does not develop → amenorrhoea. It is also this deficiency in oestrogen and progesterone that results in the symptoms that occur in menopause.
😷 Presentation
In summary, the symptoms associated with perimenopause and menopause include:
- Hot flushes and night sweats
- Emotional lability and/or depression
- Irregular periods
- Heavier or lighter periods
- Joint pains
- Vaginal dryness and atrophy
- Dyspareunia and post-coital bleeding
- Reduced libido
- Urinary incontinence, recurrent UTI, dysuria
- Sleep disturbances
- Weight gain and increased adiposity
- Vasomotor symptoms (hot flushes and night sweats) - this is among the most common symptoms of menopause. They are most prevalent in the perimenopausal state and usually present for up to 5 years at most but around 8% of women suffer from the vasomotor symptoms for up to 20 years in the postmenopausal period.
- Sexual dysfunction - this is a multi-factorial issue that occurs during early-late menopausal transition.
- Vaginal dryness - due to declining levels of oestrogen. This may subsequently lead to dyspareunia.
- Low androgen levels - supposedly leads to low libido but evidence is conflicting.
- Non-hormonal factors - such as conflict between partners, life stress, depression (associated with menopause). These all contribute to decreased sexual dysfunction.
- Psychological problems - such as:
- Depressed mood
- Anxiety
- Irritability and mood swings
- Lethargy and lack of energy
The factors that result in sexual dysfunction include:
- Osteoporosis - osteoporosis affects 1 in 3 women (compared in 1 in 12 men). Osteoporosis itself is not symptomatic but fractures may occur, most commonly at the distal radius (Colle’s fracture), neck of femur and vertebrae. We will discuss more on osteoporosis in the page on it found in the orthopaedics section.
- Bone density - determined by peak bone mass and the amount of bone loss.
- Bone quality - this refers to the architecture of the bone, turnover, damage accumulation and mineralisation of the bone.
- Cardiovascular disease - MI and stroke are the biggest concerns. This is driven by changes that occur with ageing, increased adiposity, insulin resistance, modified lipid profile, an increase in low-density lipoprotein and triglycerides and a decrease in high-density lipoprotein.
- Urogenital atrophy (now referred to as genitourinary syndrome of menopause) - this is because oestrogen receptors and progesterone receptors are present in the vagina, urethra and bladder as well as pelvic floor. A deficiency in oestrogen results in atrophic changes and urinary symptoms such as frequency, urgency, nocturia, incontinence, recurrent UTI. It may coexist with other issues associated with vaginal atrophy such as dyspareunia, itching, burning and dryness.
Bone strength encompasses 2 features:
🔍 Investigations
⭐️ A diagnosis of perimenopause and menopause can be made clinically without investigations in a women >45 years old with typical symptoms.
NICE recommends performing a serum FSH level to aid diagnosis in women that are:
- <40 years old with suspected premature menopause
- 40-45 years old with alterations to their menstrual cycle or have menopausal symptoms (i.e. suspected early menopause).
🧰 Management
We have options for management that include lifestyle advice and education, hormonal treatments and non-hormonal treatments as well.
- First of all patient education on what menopause is, the short-term and long-term consequences, and the management options needs to be discussed.
- Hot flushes → regular exercise, weight loss, stress reduction, keeping cool etc.
- Sleep disturbances → maintain good sleep hygiene and avoid late exercise.
- Advise patients on contraceptive use as the women may still be fertile and that women should still take contraception for the following durations:
- 2 years after LMP in women <50 - they may be offered combined hormonal contraception prior to 50 years of age.
- 1 year after LMP in women >50 - it should be progestogen-only at 50 years of age.
All women may stop contraception at the age of 55.
The aim of HRT is to replace the body’s supply of oestrogen to mitigate the associated issues that come with oestrogen deficiency. We will first discuss the choices of HRT used depending on the symptoms present and then we will discuss the more practical aspects of HRT.
Once HRT has been started → arrange to review after 3 months then annually thereafter.
We can stop HRT gradually over 3-6 months or suddenly depending on patient preference.
🔥 Vasomotor symptoms
- Women with a uterus → offer oral/transdermal combined HRT (oestradiol + progestogen). This is because the addition of a progestogen opposes the endometrial thickening caused by oestrogen.
- Women without a uterus → offer oral/trandermal oestrogen-only HRT. This is because there is no need for the protective effect to the endometrium provided by progesterone.
- In women <50 → offer combined HRT OR combined hormonal contraceptive as an alternative if there are no contraindications (such as VTE risk, >35 years of age, high BMI etc.). The difference between HRT and contraceptives is the dosage given as HRT has a much lower dosage compared to contraceptives.
- Isoflavones (such as soybeans) or black cohosh herb can be used as dietary supplements to relieve the hot flushes.
The treatment should be continued for as long as needed for symptomatic relief (usually 2-5 years for vasomotor symptoms)
🧠 Psychological symptoms
- Oral/transdermal HRT
💦 Urogenital symptoms (genitourinary symptoms of menopause)
- 🥇 Low-dose vaginal oestrogen - is the first-line option and if this is not sufficient then the dose should be increased as a second-line option.
- 🥇 Vaginal moisturisers/lubricants - can be used alone or together with vaginal oestrogen.
- 🥈 Ospemifene - this is a SERM with an agonistic effect on the endometrium, vagina and bone oestrogen receptors while being an antagonist in breast tissue).
🫦 Altered sexual function
- Testosterone preparations may be given via implants or patches but this is an off-label use of testosterone.
- Women at increased risk of breast cancer should not be offered HRT, and if on it they must stop it. This includes the use of isoflavones and black cohosh. They should be advised on lifestyle options and non-pharmacological options or non-hormonal options instead.
- Women with an increased risk of VTE and cardiovascular disease (e.g. obesity, hyperlipidaemia, hypertension etc.) should have their risk factors managed prior to consideration of HRT. If they do begin HRT, then transdermal HRT is preferred to oral HRT .
- Women with hypothyroidism should have their TSH monitored 6-12 weeks after starting oral HRT to assess if the levothyroxine dosage needs to be increased.
[TO INCLUDE SECTION ON HRT MEDICATIONS, CYCLES, ADVERSE EFFECTS, RISKS, CONTRAINDICATIONS]
If HRT is not tolerated, contraindicated or simply refused by the woman then we should:
- Offer lifestyle advice
- Consider non-drug treatments or non-hormonal pharmacological options.
🔥 Vasomotor symptoms
Options include:
- SSRI/SNRI or clonidine or gabapentin
- Cognitive behavioural therapy (CBT)
🧠 Psychological symptoms
- Self-help resources and a trial of CBT for low mood/anxiety.
- If there is a confirmed diagnosis of depression and/or anxiety we can manage it accordingly.
💦 Urogenital symptoms (genitourinary symptoms of menopause)
- Vaginal moisturisers and lubricants. The moisturisers help with dryness and long-term relief while the lubricants are for comfort during sexual activity and immediate relief.
💡 It is important to be aware that if there is a sudden change in the menstrual pattern, intermenstrual bleeding, post-coital bleeding or post-menopausal bleeding then women should be referred via the 2-week wait pathway to gynaecology.
POI is a syndrome defined as the transient or permanent loss of ovarian function prior to the age of 40 years old. It is characterised by menstrual disturbances (such as amenorrhoea or oligomenorrhoea), elevated gonadotrophins and oestrogen deficiency.
There may be instances of spontaneous resumption of ovulation, menstruation and spontaneous pregnancy.
Causes of POI:
We can divide them into primary and secondary causes of POI:
Primary causes:
- Chromosomal abnormalities
- FSH receptor gene polymorphism and inhibin B mutation
- Enzymatic deficiences
- Autoimmune disease
- Family history of premature menopause
Secondary causes:
- Chemotherapy
- Radiotherapy
- Bilateral oophorectomy
- Hysterectomy without oophorectomy
- Infection
🔍 Investigations:
- Serum FSH levels - two samples should be taken (4-6 weeks apart). 2 raised levels (>30IU/L) is diagnostic for POI.
🧰 Management
HRT is the mainstay of management and should be taken up to the average age of natural menopause (51 years in the UK). After this age the need for continuation may be reassessed.