Endometriosis Injections Every 3 Months and No Periods: Night Chills and Hot Flashes, Insomnia, Weight Gain, Bloating, What Magnesium Can and Cannot Do, and Protecting Your Bones

From our reader group: injections every 3 months, no periods, and menopause-like symptoms

A member in her early 40s is treating endometriosis with an injection every 3 months and has not had a period for a long time.
Lately she has night chills alternating with heat, trouble falling asleep, night waking, fatigue, weight gain and bloating. She takes magnesium and keeps every injection appointment.
Several others in the group asked similar questions: are these symptoms from the drug, and what can they do?

Short answer: this cluster fits low estrogen caused by ovarian suppression, which is expected and manageable.
The first thing to know is the name of the drug, because the two injection groups affect symptoms and bone differently. For the broader hormone-therapy picture, read
Severe period pain, chocolate cysts, and an enlarged uterus: hormone therapy and caring for your heart

1. What kinds of 3-monthly injections are there, and why do periods stop?

Direct answer: three-monthly injections for endometriosis fall into two main groups: injectable progestin medroxyprogesterone acetate, and 3-month depot GnRH agonists.
Both relieve pain to a similar degree, but GnRH agonists suppress estrogen more deeply, so hot flashes are more common and bone thins faster
(Schlaff 2006,
Crosignani 2006).

Group 1: medroxyprogesterone acetate (DMPA)

A progestin that blocks ovulation and makes endometriosis lesions shrink. It comes as a 150 mg intramuscular injection or a 104 mg subcutaneous injection every 3 months.
In a trial of 274 patients, the subcutaneous form relieved pain as well as leuprorelin, with fewer low-estrogen symptoms and less bone loss, but more irregular bleeding
(Schlaff 2006).

Group 2: 3-month GnRH agonists

These include leuprorelin 11.25 mg, triptorelin 11.25 mg and goserelin 10.8 mg. Continuous stimulation of the pituitary makes its GnRH receptors stop responding; LH and FSH fall, and the ovaries stop making estrogen, down to levels close to those after menopause.
Symptoms therefore look very much like menopause, and they reverse after the drug is stopped
(Hornstein 1998).

In your early 40s, should natural menopause be considered too?

At this age some women’s ovaries begin to slow down naturally. While the ovaries are suppressed by injections, blood hormone tests are hard to interpret, so doctors usually look at symptoms, treatment duration and what happens after stopping.
The drugs do not cause permanent menopause, but if you reach natural menopause age during treatment, periods may not return after stopping.

2. Night chills alternating with heat, and insomnia: what causes them

Direct answer: when estrogen is low, the brain’s temperature-control center becomes more sensitive, and the body dumps heat through the skin and sweat as soon as core temperature rises slightly.
As the sweat evaporates, chills follow, so you feel cold and hot in turns, and night episodes wake you repeatedly
(NAMS 2023).

How strong the symptoms are depends on the drug

In a head-to-head trial, women on a GnRH agonist had more low-estrogen symptoms than women on subcutaneous medroxyprogesterone acetate
(Schlaff 2006).
Even with newer oral relugolix, combined in one tablet with low-dose estrogen and progestin, hot flushes were still among the most common side effects
(Giudice 2022).

How to protect your sleep

• If heat and sweating wake you, reducing hot flashes treats the cause. If you are on a GnRH agonist, ask your doctor about add-back therapy
• Cognitive behavioral therapy for insomnia (CBT-I) is the first-line treatment for chronic insomnia in adults
  (Qaseem 2016)
• Keep fixed bed and wake times, get up if you cannot sleep within 20 minutes, skip coffee after noon, and skip alcohol, which can trigger hot flashes
• A cool bedroom, several thin layers of bedding, sweat-wicking sleepwear and a spare top by the bed help you get back to sleep faster

Fatigue and mood

Fatigue usually follows broken sleep. A placebo-controlled study found that depressive symptoms increased in women treated with GnRH agonists for endometriosis, and that these symptoms respond to treatment
(Warnock 1998).
If low mood lasts more than 2 weeks, tell your doctor rather than enduring it until the course ends.

3. What magnesium can do: sleep, hot flashes and the gut

Direct answer: the sleep evidence is small and low quality, and for hot flashes a large trial found magnesium no better than placebo.
Magnesium does loosen stools by drawing water into the bowel, which helps constipation but can cause diarrhea
(Mah 2021,
Park 2015).

Sleep

A pooled analysis of 3 trials in 151 older adults found magnesium shortened time to fall asleep by 17.36 minutes versus placebo; total sleep time rose by 16 minutes but not significantly.
All trials had moderate-to-high risk of bias, and none studied women on ovarian-suppressing drugs
(Mah 2021).

Hot flashes

A double-blind randomized trial in 289 women with bothersome hot flashes compared magnesium oxide 800 or 1,200 mg a day with placebo. Hot flash scores and frequency did not differ.
The magnesium groups had more diarrhea and less constipation
(Park 2015).

Using it safely

• The tolerable upper intake level from supplements for adults is 350 mg a day, not counting magnesium from food
  (NIH ODS)
• People with advanced chronic kidney disease clear magnesium poorly and can develop high blood levels; ask your doctor first
  (Cunningham 2012)
• If you get diarrhea, lower the dose or stop. Magnesium can reduce absorption of some drugs, such as tetracycline and quinolone antibiotics; take them at least 2 hours apart

4. Weight gain and bloating: how much is the injection to blame?

Direct answer: the evidence for weight gain is clearer with medroxyprogesterone acetate, while bloating is already common in endometriosis itself.
(Berenson 2009,
Simons 2024)

How much weight

A cohort of 703 women followed with body-composition scans found DMPA users gained 5.1 kg of weight and 4.1 kg of fat, with more central fat, over 36 months, more than pill users and non-hormonal users
(Berenson 2009).
A Cochrane review found most studies showed mean gains under 2 kg at 6–12 months, with low-quality evidence overall
(Lopez 2016).
In the trial comparing subcutaneous DMPA with leuprorelin, weight change did not differ
(Schlaff 2006).

Bloating and constipation

Up to 90% of people with endometriosis have gut symptoms such as constipation, bloating and nausea, and their risk of irritable bowel syndrome is 3–5 times that of other women
(Simons 2024).
Bloating may therefore come from the disease, overlapping IBS, or changes in eating and activity from poor sleep, more than from the injection alone.

What you can do

• Weigh yourself weekly at the same time; if you gain more than 2–3 kg in 3 months, mention it at your injection visit
• Protein at every meal, vegetables and whole grains, fewer sugary drinks, which help with fullness and bowel habits
• Resistance exercise 2–3 days a week helps preserve muscle and loads the bones
• If bloating comes with blood in the stool, unintended weight loss or frequent vomiting, see a doctor instead of adding more magnesium

Table: symptoms during injections, causes, and what helps

Summarized from the studies in this article; symptoms vary with the drug, duration and other conditions.

5. How much bone is lost, and what is add-back therapy?

Direct answer: a GnRH agonist used for 12 months without add-back lowered spine bone density by 6.3%, while groups given add-back therapy kept their bone density stable.
Medroxyprogesterone acetate thins bone more slowly, and bone recovers after stopping
(Hornstein 1998,
Kaunitz 2006).

Figures come from different studies and durations; use them to see the trend, not as a direct comparison (Hornstein 1998, Kaunitz 2006, Desilets 2026, Giudice 2022).

GnRH agonists: fast loss, add-back helps

In a trial of 201 patients given leuprorelin every 4 weeks for 1 year, the placebo group lost 6.3% of bone density, while groups given norethisterone acetate 5 mg a day, alone or with low-dose estrogen, kept bone density stable with the same pain relief
(Hornstein 1998).
In follow-up after stopping, the group without add-back recovered slowly and had not returned to baseline at the final visit
(Surrey 2002).
The 2022 ESHRE guideline therefore recommends considering add-back therapy alongside GnRH agonists to prevent bone loss and reduce low-estrogen symptoms
(ESHRE 2022).

DMPA: slower loss, and recoverable

Women aged 25–35 using intramuscular DMPA for 240 weeks lost 5.16% at the hip and 5.38% at the spine; 96 weeks after stopping, the losses were −0.20% and −1.19%
(Kaunitz 2006).
A review of 10 studies found bone density returned to or toward baseline after stopping, at all ages
(Kaunitz 2008).
The US label still carries a boxed warning about bone with continuous use beyond 2 years
(Cromer 2006).

What add-back therapy is

It means giving low doses of hormone back during ovarian suppression, such as norethisterone acetate alone or low-dose estrogen with a progestin.
The rationale is the estrogen threshold hypothesis: tissues differ in estrogen sensitivity, so a level that partly protects bone may not reactivate endometriosis pain
(Barbieri 1992).
A meta-analysis found GnRH agonists with add-back still lowered bone density slightly, by 0.89% at 6 months and 1.50% at 12 months
(Desilets 2026).
People with a history of blood clots, stroke or hormone-sensitive cancer need a doctor’s assessment before using estrogen.

Calcium, vitamin D and vitamin K2

• Women aged 19–50 need 1,000 mg of calcium a day; start with food such as milk, firm tofu, small whole fish and leafy greens, then supplement only the gap
  (NIH ODS Calcium)
• Calcium citrate is absorbed with or without food, while calcium carbonate is absorbed best with food; both work, and citrate is not always required
• Vitamin D 600 IU a day is the general adult recommendation; people who are deficient may need more based on blood tests
• Vitamin K2: a Japanese trial used menatetrenone 45 mg a day, a prescription drug, and partly reduced leuprorelin bone loss from −5.25% to −3.59% over 6 months, without preventing it fully
  (Somekawa 1999).
  Low-dose over-the-counter K2 supplements have not been studied in this setting, and people taking warfarin must ask their doctor first

Table: bone-care roadmap by drug and duration

Figures from the trials and cohorts in this article. Bone density scans (DEXA) and add-back depend on your doctor’s assessment.

6. Comparing treatment and symptom-care options

Comparison table: ovarian suppression, add-back, and symptom care

Generic drug names and classes are for education only; choosing or switching drugs requires your doctor’s assessment.

Myths worth correcting

The injections put you into permanent menopause

Ovarian suppression is temporary and the ovaries resume after stopping, unless you happen to reach natural menopause age during that time.

Magnesium is a GABA agonist that gives deep sleep without sleeping pills

Human evidence comes from only 3 small, low-quality trials showing about 17 minutes faster sleep onset. Chronic insomnia should start with CBT-I and with treating the hot flashes that wake you.

Magnesium stops night chills and heat

A randomized trial of 289 women found magnesium oxide reduced hot flashes no more than placebo. If you are on a GnRH agonist, ask your doctor about add-back therapy instead.

Calcium, D3 and K2 fully prevent bone loss from injections

Enough calcium and vitamin D is a foundation, but it does not stop bone loss caused by low estrogen. Prescription-dose vitamin K2 helped only partly. What clearly protects bone on GnRH agonists is add-back therapy.

If side effects are bad, delay or skip the next injection yourself

Stopping on your own may bring the pain back. Take your symptom diary to your doctor, who has several options, from adding add-back to switching injection type or moving to an oral drug.

Weight gain from the drug cannot be changed

Weight gain on DMPA varies widely. Most studies show a mean gain under 2 kg in the first year, and some comes off after stopping. Protein and resistance exercise still help.

Frequently asked questions (FAQ)

What kinds of 3-monthly endometriosis injections are there, and why do periods stop?

There are two main groups: medroxyprogesterone acetate given into muscle or under the skin, and 3-month depot GnRH agonists such as leuprorelin, triptorelin and goserelin. Both block ovulation and shrink lesions, so periods stop. GnRH agonists suppress estrogen more deeply, so menopause-like symptoms are more common.

Why do I get night chills alternating with heat and sweating?

Low estrogen makes the brain’s temperature-control center more sensitive. When core temperature rises slightly, the body widens skin blood vessels and sweats at once; as sweat evaporates, chills follow. These symptoms are more common with GnRH agonists than with medroxyprogesterone acetate.

What should I do about insomnia and night waking during injections?

If heat and sweating wake you, talk to your doctor about reducing hot flashes, for example with add-back therapy on a GnRH agonist. For chronic insomnia, cognitive behavioral therapy for insomnia (CBT-I) is first-line, together with fixed sleep and wake times, a cool bedroom, no coffee after noon and no alcohol.

Does magnesium really help sleep and hot flashes?

For sleep, a pooled analysis of 3 trials in 151 people found about 17 minutes faster sleep onset, but the evidence is low quality. For hot flashes, a randomized trial of 289 women found magnesium no better than placebo. You can continue at up to 350 mg a day from supplements if you do not have advanced kidney disease, but it should not replace medical treatment.

Are weight gain and bloating caused by the injection?

Weight gain has evidence with medroxyprogesterone acetate: a 3-year cohort found a mean gain of 5.1 kg, though most studies show under 2 kg in the first year. Bloating affects up to 90% of people with endometriosis because of the disease and overlapping IBS. If bloating comes with blood in the stool or weight loss, see a doctor.

How much bone do the injections take, and does it come back?

A GnRH agonist used for 12 months without add-back lowered spine bone density by 6.3%, with slow recovery after stopping. Intramuscular medroxyprogesterone acetate used for about 4.6 years lowered it by about 5%, and it nearly recovered within 96 weeks of stopping.

What is add-back therapy, and who should get it?

It is low-dose hormone given alongside ovarian suppression, such as norethisterone acetate alone or with low-dose estrogen. It reduces hot flashes and prevents bone loss without reducing pain relief. The 2022 ESHRE guideline recommends considering it for people on GnRH agonists. People with past blood clots or hormone-sensitive cancer need a doctor’s assessment first.

Should I take calcium, vitamin D and vitamin K2?

Aim for 1,000 mg of calcium a day in total, starting with food, and enough vitamin D. Calcium citrate and carbonate both work. Prescription-dose vitamin K2 partly reduced leuprorelin bone loss in one trial but did not fully prevent it, and low-dose supplements have not been studied in this setting.

Scientific Mechanism

How GnRH agonists suppress the ovaries: normally the pituitary receives GnRH in pulses. A GnRH agonist released continuously stimulates the receptors all the time, until the cells reduce their receptors and stop responding.
LH and FSH fall, the ovaries stop making estrogen, and estrogen-dependent lesions shrink, while bone, brain and skin also lose estrogen
(Hornstein 1998).

How DMPA works differently: medroxyprogesterone acetate is a progestin that blocks the mid-cycle LH surge, so ovulation does not occur, and it directly makes the lining and lesions atrophy.
Estrogen falls, but not as deeply as with GnRH agonists, which explains why hot flashes and bone loss are smaller
(Crosignani 2006).

Why bone thins, and how add-back helps: estrogen restrains bone-resorbing cells. When estrogen is low, resorption outpaces formation.
The estrogen threshold hypothesis explains that bone is more sensitive to estrogen than endometriosis lesions, so low-dose hormone can protect bone without bringing the pain back
(Barbieri 1992).

How night chills and heat arise: with low estrogen, KNDy neurons in the hypothalamus send more neurokinin B signaling, and the body’s tolerated temperature range narrows.
A small rise in temperature triggers heat loss, followed by chills as the sweat evaporates
(NAMS 2023).

Compiled and reviewed by Asst. Prof. Dr. Norawit Raatpiboon

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