IB Biology HLTopic 4 — Genetics, Inheritance & ChangePaper 1 & 2Nature of science~10 min read
Hormone Replacement Therapy
This page is really two topics. One is the biology of the menopause and how HRT works. The other is a genuinely famous scientific misstep — a correlation that everyone read as a cause, and what it took to find out otherwise. The IB wants both.
📚 What you need to know
The menopause is when a female stops having periods for longer than 12 months. It is a natural part of ageing, usually between 45 and 55.
During the menopause the ovaries stop ovulating and stop producing most of their oestrogen and progesterone, because they no longer respond to FSH and LH.
With less oestrogen and progesterone there is no longer a negative feedback loop to the pituitary, so LH and FSH levels increase.
Symptoms can include hot flushes, breast tenderness, headaches, sleep issues and emotional changes.
HRT replaces oestrogen and progesterone, usually as a tablet, patch, cream or gel, and can reduce the symptoms.
Early observational studies suggested HRT reduced the risk of coronary heart disease (CHD), and this was treated as cause and effect.
Later randomised controlled trials in the 1990s showed HRT may cause a small increase in CHD risk.
The timing hypothesis and socioeconomic status both help explain the contradiction.
What happens at the menopause
Follow the chain and every symptom makes sense. The ovaries stop responding to FSH and LH, so they stop ovulating and stop producing most of their oestrogen and progesterone.
Now think about what those two hormones were doing to the pituitary. Throughout the reproductive years they inhibited FSH and LH secretion — the negative feedback you met on the menstrual cycle page. Remove the oestrogen and progesterone and that inhibition disappears, so FSH and LH levels rise. High FSH is in fact used clinically as an indicator that the menopause has occurred.
The pituitary has not changed. It is simply no longer being told to slow down, because the ovaries have stopped sending the signal.
How HRT works
HRT is a treatment used to relieve the symptoms of the menopause by replacing the hormones oestrogen and progesterone. Oestrogen has effects all over the body, including on blood vessels, bone strength, the skin, the urinary tract, the uterus and the brain — which is why its loss produces such a wide range of symptoms. Taking synthetic oestrogen as a tablet, patch, cream or gel can reduce them.
Notice the logic of the treatment. HRT does not restart the ovaries. It supplies from outside what the ovaries have stopped supplying from inside, which is why it treats symptoms rather than reversing the menopause.
Nature of science: correlation is not causation
This is the part of the page examiners love, so learn it as a story with a sequence.
🧩 How the evidence changed
Around 40 years ago, an epidemiological observational study found that women taking HRT had a lower risk of coronary heart disease than those who did not.
The effect was deemed to be a cause-and-effect relationship, and many women chose, and were advised, to take HRT for this benefit.
Randomised controlled trials in the 1990s then showed that use of HRT may cause a small increase in the risk of heart disease.
Newer evidence suggests a timing hypothesis: HRT started in the early years of the menopause does benefit the heart, with reduced CHD risk. The randomised trials included many women who were several years postmenopausal, whereas the observational studies included women in their early menopausal years.
The original correlation was also confounded. In general, women who take HRT are more educated, wealthier, have healthier lifestyles and have fewer cardiovascular risk factors. A meta-analysis showed the apparent reduced risk shrank once socioeconomic status was included in the analysis.
Why the two study types disagreed
The difference is not that one set of scientists was careless. It is structural.
An observational study compares people who have already chosen whether to take a treatment. Those groups differ in many ways besides the treatment, and any of those differences — wealth, diet, exercise, access to healthcare — could be the real cause of the outcome. These are confounding variables.
A randomised controlled trial assigns the treatment at random. On average, the confounding variables are then spread evenly between the groups, so a difference in outcome is far more likely to be caused by the treatment itself. That is why the RCT result was taken to overturn the observational one.
If you are asked to evaluate any epidemiological claim, three phrases do most of the work: correlation does not imply causation, confounding variables and randomised controlled trial. This HRT case is the IB’s worked example of all three.
Worked examples
WORKED EXAMPLE
Explain why FSH and LH levels increase during the menopause. [3]
Point 1 — the ovaries
During the menopause the ovaries stop responding to FSH and LH and stop producing most of their oestrogen and progesterone.
Point 2 — the feedback
Oestrogen and progesterone normally inhibit the secretion of FSH and LH from the pituitary gland by negative feedback.
Point 3 — the result
With their levels reduced, this inhibition is lost, so the pituitary continues secreting FSH and LH and their levels in the blood rise.
3 marksName the loop as negative feedback. It is usually a separate mark.
WORKED EXAMPLE
Early observational studies concluded that HRT reduces the risk of coronary heart disease. Evaluate this conclusion. [4]
Point 1 — what the data showed
The studies found a correlation: women taking HRT had a lower incidence of CHD than women who did not.
Point 2 — the flaw
A correlation from an observational study does not establish cause and effect, because the two groups were not assigned at random.
Point 3 — confounding variables
Women who take HRT tend to be wealthier and more educated, with healthier lifestyles and fewer cardiovascular risk factors, and a meta-analysis showed the apparent benefit shrank once socioeconomic status was accounted for.
Point 4 — the stronger evidence
Randomised controlled trials in the 1990s found a small increase in CHD risk, although the timing hypothesis suggests the age at which HRT is started matters.
4 marksAn evaluate question wants both sides. The timing hypothesis stops this being a simple “the first study was wrong”.
💡 Exam tip
Use the exact phrase correlation does not imply causation when evaluating epidemiological data.
Name at least one specific confounding variable — socioeconomic status is the one to remember here.
Explain why an RCT is stronger: random assignment spreads confounding variables evenly.
Do not present the story as “scientists were wrong”. Present it as evidence improving over time.
For the menopause itself, always route the answer through negative feedback.
The timing hypothesis is the detail that separates a top answer from a standard one.
⚠ Common mix-up
The pituitary does not fail at the menopause. The ovaries stop responding to it.
Rising FSH is not the cause of the menopause. It is a result of it.
HRT does not restart ovulation. It replaces hormones to relieve symptoms.
Observational studies are not worthless. They generate hypotheses that trials can then test.
A meta-analysis is not a new experiment. It combines and reanalyses existing studies.
The evidence is not simply “HRT is bad for the heart”. Timing of treatment changes the picture.
That completes Reproduction. From here the topic chain continues into inheritance and genetic variation — everything on these thirteen pages was building the mechanism by which alleles get passed on in the first place.
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